BME Seminar Series

BME-Seminar

About

The Department of Biomedical Engineering Seminar Series consists of presentations on current research topics of interest to biomedical engineering graduate students and faculty by on-campus and visiting engineers and scientists.Seminars are recorded and archived: Visit the Video Archive Here (login required)

Corrine Bahr Memorial Lecture

The BME department began with just three tenured faculty – and Corrine, our department administrator who did everything possible to support us and to help us succeed. Corrine felt that graduate students needed special attention since they come from so many different places and cultures from around the country and around the world. One of her special projects was welcoming graduate students and helping them to feel at home here. Because of this role, BME graduate students select the speaker for this honorary lecture.

Seminar Schedule

Unless otherwise noted, seminars will be scheduled:

Mondays from 12 – 1 PM

Room 1003 (Tong Auditorium) in the Engineering Centers Building

Fall 2017 Seminar Series

 

Growth factor signaling and metabolic homeostasis in single cells

Speaker: John Albeck 

Assistant Professor, Molecular & Cellular Biology, UC-Davis


Time and Location: 

12 – 1 PM

1003 Engineering Centers (Tong Auditorium)


Abstract:

As single-cell technologies expand, it is becoming clear that many cellular signaling events are very dynamic, necessitating a time-lapse approach to capture rapid kinetics within the cell.  I will present our work on using live-cell imaging with genetically encoded reporters to approach two long-standing questions in the regulation of cell growth in humans. This work centers on two kinases – ERK and AMPK  – that play key roles in homeostasis of healthy tissues and which are currently being targeted by cancer therapies.  The first question is how the dynamics of ERK activity encode information from extracellular stimuli, allowing different growth factor receptors to activate distinct gene expression programs using the same intermediate signaling pathways. Mutations in this pathway, and candidate therapies targeting these mutations, exert unique effects on ERK kinetics, making it essential to decode the cellular “language” of ERK activity dynamics.  The second question is how cellular energetics are maintained and balanced despite continuing fluctuations in both the supply of nutrients and the demand created by anabolic processes required for cell growth.  We find that the interlinked AMPK, Akt, and ERK pathways undergo surprisingly dynamic fluctuations in response to metabolic stresses, suggesting new models for how cellular homeostasis is maintained on the scale of minutes by coordination of catabolic and anabolic processes.

 

 

Static & Dynamic Measures of Human Brain Connectivity Predict Complementary Aspects of Human Cognitive Performance

Speaker: Michael Deem

Department Chair of Bioengineering at Rice University

John W. Cox Professor in Biochemical & Genetic Engineering

Professor, Physics & Astronomy

Founding Director, Ph.D. Program in Systems, Synthetic, & Physical Biology (SSPB)


Time and Location: 

12 – 1 PM

1003 Engineering Centers (Tong Auditorium)


Abstract:

I will discuss the relationship between modularity of neural activity in the
brain and cognitive ability, reviewing observations and theories relating
modularity to plasticity of brain neural activity.

 

By analogy with evolutionary biology, I hypothesize that selection for maximum plasticity of the human brain occurs in young adulthood, which implies modularity should peak in young adults. I will show that modularity of neural activity derived from fMRI data rises from childhood, peaks in young adults, and declines in older adults. I will review experiments being carried out by collaborators at Rice to answer three innovative applications in cognitive neuroscience:

  1. the relation among modularity, task complexity, and performance in the human
    brain
  2. the relation of task complexity to hierarchical scale of neural
    activity
  3. the predictive power of resting state measurements for
    performance on specific tasks.

I will also briefly describe how modularity helps to understand structure and performance in gene networks, with applications to cancer metastasis and recurrence.

Spatiotemporal Organization of the E. coli Cytoplasm

Speaker: James Weisshaar

Richard J. Burke Professor of Chemistry at the University of Wisconsin-Madison


Time and Location: 

12 – 1 PM

1003 Engineering Centers (Tong Auditorium)


Abstract:

Superresolution fluorescence microscopy has enabled us to locate and track single ribosomes, RNA polymerase copies, ribosomal elongation factors EF-P and EF-Tu, and DNA loci in live E. coli cells. Spatial localization accuracy can be s σ ~ 30 nm and the time resolution can be 2-10 ms when needed. Ribosome-RNAP segregation is strong, arguing against co-transcriptional translation as the primary means of protein synthesis. Diffusion of both ribosomes and RNAP is heterogeneous. This enables us to distinguish translating 70S-polysomes from 30S subunits searching for translation initiation sites. We can also distinguish transcribing RNAP copies from those searching for transcription initiation sites. The combination of these new experimental data with coarse-grained models of DNA-ribosome mixing suggests a picture in which expansion of the nucleoid by transertion (co-translational transcription and simultaneous membrane protein insertion) is important for optimal cell function. The expanded nucleoid enables facile recycling of ribosomal subunits from ribosome-rich regions (where most translation occurs) to the nucleoids (where they can initiate co-transcriptional translation). At the same time, free polysomes are excluded from the nucleoids. The resulting spatial segregation may enhance overall growth rate by restricting the space within which RNAP searches for transcription initiation sites and ribosomal subunits search for translation initiation sites.

Graduate Panel: Neuromuscular Biomechanics

Speaker: Members of the UW Neuromuscular Biomechanics Lab

Michael Vignos, Jack Martin, & Colin Smith


Time and Location: 

12 – 1 PM

1003 Engineering Centers (Tong Auditorium)


Abstract 1:

Graft Geometry is Linked with Asymmetric Knee Mechanics Following ACL-Reconstruction

Michael Vignos; Ph.D. Candidate, UW-Madison Mechanical Engineering

The long-term prognosis of ACL-reconstruction is concerning, given that >50% of patients develop early osteoarthritis at 10-15 years post-surgery. This high incidence rate is believed to be caused, in part, by abnormal cartilage loading that remains following surgery.

In this work, we seek to assist orthopedic surgeons in restoring normal cartilage loading patterns by investigating the relationship between controllable surgical factors, such as ACL-reconstruction graft geometry, and post-operative knee mechanics. A combination of experimental and computational methods are used to determine the effect of variations in ACL-graft placement on knee kinematics and cartilage contact.

Abstract 2:

Gauging Force by Tapping Tendons

Jack Martin; Ph.D. Candidate, UW-Madison Materials Science & Engineering

Muscle-tendon force estimates are fundamental to the study and treatment of various musculoskeletal disorders, injuries and diseases.

However, current methods for determining these forces are highly limited. Modeling approaches rely on many assumptions relating to neuromuscular coordination and tissue geometry, while direct measurement approaches are highly invasive. 

In this talk, I will discuss the basis for—and early implementation of—a novel technique for non-invasive tendon stress measurement. This technique is based on generating and tracking shear waves in tendon, where shear wave speed is directly related to tendon stress. The ability it gives us to non-invasively measure tendon stresses has a number of potential applications within clinical and research biomechanics.

Abstract 3:

Can Altered Neuromusclar Coordination Restore Healthy Cartilage Loading Following ACL Injury?

Colin Smith; Ph.D. Candidate, UW-Madison Mechanical Engineering

Current ACL injury treatments arelargely successful in restoring knee stability and function. However, long-term outcomes are sub-optimal, as ~ 50% of patients develop early onset osteoarthritis (OA). Restoring cartilage loading patterns during functional movements is key to preventing disruption of cartilage tissue homeostais and early onset OA. While surgical techniques are now evaluated on their ability to restore pre-injury knee kinematics and loading, it is unknown whether this goal is achievable throughconservative treatment. In this talk, I will present a musculoskeletal simulation framework to predict cartilage loading during walking and investigate whetherhealthy cartilage loading can be restoredin ACL deficient knees through neuromuscular retraining.

 


 

 

 

 

Topic TBA

 

SpeakerLaura Waller

Associate Profesor of Electrical Engineering & Computer Science at UC-Berkeley


Time and Location: 

12 – 1 PM

1003 Engineering Centers (Tong Auditorium)


Abstract:

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Speaker, Topic TBA

 

 

 

 

 

 


 

Topic TBA

SpeakerSuhasa Kodandaramaiah

Benjamin Mayhugh Assistant Professor in Mechanical Engineering at the University of Minnesota


Time and Location: 

12 – 1 PM

1003 Engineering Centers (Tong Auditorium)


Abstract:

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Topic TBA

Speaker: Manu Platt

 

Associate Professor of Biomedical Engineering at Georgia Tech

Wallace H. Coulter Department of Biomedical Engineering Diversity Director

STC on Emergent Behaviors of Integrated Cellular Systems (EBICS), GRA Distinguished Scholar


Time and Location: 

12 – 1 PM

1003 Engineering Centers (Tong Auditorium)


Abstract:

TBA

 


 

Topic, Speaker TBA

Topic, Speaker TBA

Archived Seminars

Date Topic Speaker
Monday
1/23/2017
Solid Stress and Elastic Energy as Measures of Tumor Mechanopathology
(Abstract)
Hadi T. Nia, Ph.D
Postdoctoral Fellow, Massachusetts General Hospital
Harvard Medical School
Monday
1/30/2017
Fusion cytokines: A Novel Class of Biopharmaceuticals for Enabling Cancer Cellular Immunotherapy
(Abstract)
Jacques Galipeau, M.D. FRCP(C)
Don and Marilyn Anderson Prof. of Oncology, Dept. of Medicine, Assist. Dean for Therapeutics Discovery and Development
UW-Madison
Monday
2/06/2017
A MRI study of sustained neuromodulation inducted by electrical tongue stimulation in balance disorders
(Abstract)
Beth Meyerand, Ph.D.
Prof. of Biomedical Engineering and Medical Physics,
UW-Madison
Tuesday
2/14/2017
9:00 am
1025 ECB
Multifunctional polymer particles and fibers by electrohydrodynamic co-jetting
(Abstract)
Joerg Lahann, Ph.D.
Professor of Biomedical Engineering and Director of the Biointerfaces Institute
University of Michigan
Monday
2/20/2017
Towards Improving Treatment Modalities for Peripheral Arterial Disease
(Abstract)
Alexey Kamenskiy, Ph.D.
Assistant Professor, Department of Surgery
College of Medicine, University of Nebraska Medical Center
Monday
2/27/2017
Engineered Titanium Dioxide Nanotube Based Sensing Platform for Low Cost Biomedical Diagnostics in Resource Limited Settings
(Abstract)
Swomitra K. Mohanty, Ph.D.
Assistant Professor of Chemical Engineering & College of Mines and Earth Sciences
The University of Utah
Monday
3/06/2017
Translating Molecular Bioengineering from the Lab to the Patient
(Abstract)
Ashutosh Chilkoti
Alan L. Kaganov Prof. and Chair of Biomedical Engineering
Duke University
Monday
3/27/2017
Autodigestion as Mechanism for Cell Dysfunction, Disease and Death
(Abstract)
Geert W. Schmid-Schönbein
Distinguished Prof. and Chair, Department of Bioengineering
Univ. of California San Diego
Monday
4/03/2017
Adaptive Neuromodulation for Movement Disorders
(Abstract)
Aysegul Gunduz Ph.D.
Assistant Professor, Department of Biomedical Engineering
University of Florida
Monday
4/17/2017
Corrine Bahr Memorial Seminar
Photoacoustic Tomography: Ultrasonically Beating Optical Diffusion
(Abstract)
Lihong V. Wang, Ph.D.
Bren Prof. of Medical Engineering and Electrical Engineering
California Institute of Technology
Monday
4/24/2017
New perspectives on disease diagnosis: From mobile phones to molecular engineering
(Abstract)
Daniel A. Fletcher
Purnendu Chatterjee Chair in Engineering Biological Systems
Chair of Dept. of Bioengineering
Univ. of California Berkeley
Monday
5/1/2017
Graduate Student Speaker Exchange
An Integrative Circuit-Host Modeling Framework for Synthetic Biology
(Abstract)
Chen Liao
PhD student, Bioengineering
University of Illinois at Urbana-Champaign


Abstract, January 23, 2017
Solid Stress and Elastic Energy as Measures of Tumor Mechanopathology

Hadi T. Nia, Ph.D.

Solid stress and tissue stiffness affect tumor growth, invasion, metastasis and treatment. Unlike stiffness, which can be precisely mapped in tumors, the measurement of solid stresses is challenging. In this seminar, I will present three distinct and quantitative techniques to obtain two-dimensional spatial mappings of solid stress and the resulting elastic energy in excised or in situ tumors with arbitrary shapes and wide size ranges. These techniques rely on the measurement of tissue displacement after disruption of the confining structures. I will present the findings from the application of these methods in models of primary tumors and metastasis: (i) solid stress depends on both cancer cells and their microenvironment; (ii) solid stress increases with tumor size; and (iii) mechanical confinement by the surrounding tissue significantly contributes to intratumoral solid stress. Finally, I will discuss how the study of the genesis and consequences of solid stress, facilitated by the engineering principles presented in this seminar, may lead to significant discoveries and new therapies.

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Abstract, January 30, 2017
Fusion cytokines: A Novel Class of Biopharmaceuticals for Enabling Cancer Cellular Immunotherapy

Jacques Galipeau, M.D. FRCP(C)

Our group has found that the fusion of GM-CSF to members of γ-c interleukins result in the generation of novel proteins with unique signaling properties and unheralded biological effects. These fusion proteins, termed GIFT fusokines (GM-CSF Interleukin Fusion Transgenes) are the result of combining GM-CSF and a γ-common chain interleukin into a single, bi-functional polypeptide. In our experience, GIFT fusokines often confer immune cells with a gain-of-function that cannot be explained by the mere sum of their constituent moieties. They act as bi-specific ligands, coupling activated GM-CSF and interleukin receptors together to drive unique downstream signaling events. The synergy that arises from these fusions have shown great promise in their ability to modulate the immune response and overcome maladaptive biological processes that underlie diseases such as cancer and autoimmune conditions. In this seminar, I will discuss the ways in which the GIFT fusokines are able to alter the immune response, particularly in disease states, with a special emphasis on how these novel molecules may be translated into effective therapies in the clinical setting.

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Abstract, February 6, 2017
A MRI study of sustained neuromodulation inducted by electrical tongue stimulation in balance disorders

Beth Meyerand, Ph.D.

Neurostimulation has emerged as a promising approach to precisely target and modify activity within neuronal structures. The flexibility of this technique has made it a useful tool for research into normal brain function, and as a potential therapy for many neurological disorders. Electrical stimulation through the tongue offers multiple advantages over other routes of administration including access to the central nervous system without invasive surgeries, the ability to stimulate using low voltages (< 12 V), high receptor density allowing high data throughput, and a very compact stimulation device liberated from accessory equipment and the need for a permanent power source. Recent studies suggest that stimulation through the tongue can produce sustained behavioral and subjective improvements in individuals with chronic balance disorders, even when the stimulation device has been removed. We have demonstrated that physical therapy measures show information-free stimulation through the tongue, termed cranial nerve non-invasive neuromoduation (CN-NINM), can indeed produce sustained improvements in the functional deficits and subjective symptoms in subjects with balance disorders. Subsequently, we applied advanced analysis techniques to functional magnetic resonance imaging (fMRI) data in order to investigate balance-processing dysfunction in these individuals compared to healthy controls. Results suggest that balance-impaired individuals have visual motion-dependent hypersensitivity of the entire balance-processing network, extending previous findings that this hypersensitivity was limited to the visual cortices. We then compared network processing before and after individuals with balance disorders received information-free tongue stimulation. We found that CN-NINM normalizes the network response to visual-motion and likely induces sustained neuromodulation of the trigeminal nuclei of the brainstem – the site at which the incoming stimulation enters the central nervous system. Collectively, the work provides a preliminary understanding of how electrical tongue stimulation modulates the balance-processing network to produce long-term behavioral improvements in individuals with balance disorders.

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Abstract, February 14, 2017
Multifunctional polymer particles and fibers by electrohydrodynamic co-jetting

Joerg Lahann, Ph.D.

Precise control of the architecture of biodegradable materials is required for many biomedical applications, including controlled drug delivery, regenerative medicine, or simultaneous imaging and diagnosis applications. In particular, the complementary control of internal (bulk) and external (surface) features has been increasingly recognized as important design parameters for multifunctional materials. Electrohydrodynamic (EHD) co-jetting, an adaptive manufacturing process that involves transferring two or more capillary needles in a side-by-side configuration, can be used to create a wide range of multicompartmental particles and fibers with micron-to-nanometer features. This architecture can enable controlled release of multiple drugs, autonomous microactuation, or the manufacturing of fiber scaffolds with unprecedented architectural control.

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Abstract, February 20, 2017
Towards Improving Treatment Modalities for Peripheral Arterial Disease

Alexey Kamenskiy, Ph.D.

Angioplasty and stenting for atherosclerotic occlusive disease in the arteries supplying the legs (Peripheral Arterial Disease, PAD) is the most common endovascular procedure outside of the heart, but carries the highest rate of reconstruction failure. Though the underlying reasons for these poor results are not completely clear, the main arterial segment within the leg, the femoropopliteal artery, appears to be significantly different from other peripheral arteries, such as the carotid or iliac arteries, possibly because of lower blood flow, but more importantly because the femoropopliteal artery undergoes large deformations during flexion of the limb. These severe deformations are reflected clinically by the high incidence of stent fractures. The seminar will cover the biomechanics of the human femoropopliteal artery; describe new ways to measure limb flexion-induced arterial deformations; discuss mechanical properties and structure of the leg artery; and assess physiologic stresses and strains that play important roles in vascular remodeling and adaptation. We will also consider common PAD treatment devices and materials, discuss the role of patient-specific modeling in improving device and material design, and suggest potential ways to improve treatment outcomes.

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Abstract, February 27, 2017
Engineered Titanium Dioxide Nanotube Based Sensing Platform for Low Cost Biomedical Diagnostics in Resource Limited Settings

Swomitra K. Mohanty, Ph.D.

There is a real need for advanced sensing technology to address significant health disparities in resource limited environments. Diseases such as Tuberculosis (TB), effect over 9 million people a year world-wide, with another estimated 3 million being missed because of the lack of low cost tools to help manage the disease and reach patients in rural settings. In order to address this problem a good understanding of the medical, and socio-economic ecosystems present in a particular community are important. Disease-specific volatile organic compounds from human breath are considered volatile biomarkers for diagnostics and have the potential to be utilized in non-invasive rapid testing at the point of care (POC). Several diseases have associated volatile biomarkers such as lung cancer, breast cancer, diabetes, and TB. TB is of particular interest as few highly sensitive and specific POC test is available for low resource settings at a low cost. This research presents a label-free method of sensing using a TiO2 nanotube based nanomaterial developed to detect volatile biomarkers associated with TB (from the breath of patients). In this work self-aligning TiO2 nanotubes were fabricated using anodization methods and functionalized with cobalt for specific binding to the volatile biomarkers. TiO2 nanotubes have large surface area and conductivity making it suitable for electronic detection. This talk will discuss the development of a point of care tuberculosis screening technology based on breath, and how the design, deployment and application is being driven by the end-user (physicians and healthcare professionals).

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Abstract, March 6, 2017
Translating Molecular Bioengineering from the Lab to the Patient

Ashutosh Chilkoti

This talk will highlight recent work from my laboratory that illustrates the clinical translation of molecular bioengineering technologies for point-of-care clinical diagnostics and drug delivery.   In the first example, I will discuss a point-of-care diagnostic —the D4 assay — that we have developed, in which all reagents are printed and stored on a “non-fouling”—protein and cell resistant—polymer brush. The D4 assay has a speed and sensitivity that is as good or better than commercially available point-of-care tests and is far simpler, cheaper more rugged, and does not require a cold-chain.   In the area of drug delivery, I will highlight two technologies: (1) an injectable delivery system based on thermally sensitive polypeptides for the sustained and tunable release of peptide drugs from a subcutaneous injection site that we have developed for treatment of type 2 diabetes; and (2) attachment-triggered self-assembly of recombinant peptide polymers that packages small molecules into soluble polymer nanoparticles that can improve the efficacy of many cancer chemotherapeutics.

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Abstract, March, 27, 2017
Autodigestion as Mechanism for Cell Dysfunction, Disease and Death

Geert W. Schmid-Schönbein

How is it possible that one can digest biological molecules in food but not digest one’s own intestine? This question raises a fundamental issue that could be a key to understand many diseases and death. During every meal the pancreas releases a set of concentrated digestive enzymes into the small intestine, which degrade biopolymers of diverse sources as part of normal digestion.  An important mechanism that prevents autodigestion of one’s own intestine is containment of digestive enzymes in the lumen of the small intestine by the mucosal epithelial barrier.  This barrier blocks entry of the pancreatic enzymes from the lumen into the wall of the small intestine to assure one digests food and not one’s own tissue.  An increasing body of evidence suggests, however, that this protection mechanism against autodigestion may fail and lead to diseases associated with cell dysfunctions by proteolytic cleavage of membrane receptors, organ failure and death.

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Abstract, April 3, 2017
Adaptive Neuromodulation for Movement Disorders

Aysegul Gunduz, Ph.D.

The human brain consists of numerous networks distributed over space and connected over time to orchestrate meaningful interaction with the external world. Neurological disorders disrupt this interaction, as well as our control over our bodies. Deep brain stimulation (DBS) has emerged in the nineties as a neurosurgical intervention for the treatment of movement disorders. The clinical personnel that perform programming of stimulation settings (amplitude, frequency and pulse width of the electrical current) however, do not necessarily have a scientific understanding of the underlying pathology, or the physiological response to the adjustments to various stimulation parameters. Instead, they base their decisions on the observable behavioral responses and verbal response of patients. Studying the neurophysiological signatures of neurological disorders, and the aftereffects of brain stimulation would enable direct interpretation of the disorder and provide insight into treatment options that can be tailored to the current clinical condition of the patient. Our goal of this project is to study the electrophysiological underpinnings of movement disorders using next generation DBS devices capable of recording brain signals in humans, in order to responsively deliver stimulation to the current pathological state of the brain. In this talk, I will present our efforts at the University of Florida on developing closed-loop DBS for Tourette syndrome, Parkinson’s disease and essential tremor.

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Abstract, April 17, 2017
Corrine Bahr Memorial Lecture
Photoacoustic Tomography: Ultrasonically Beating Optical Diffusion

Lihong V. Wang, Ph.D.

Photoacoustic tomography (PAT), combining optical and ultrasonic waves via the photoacoustic effect, provides in vivo functional, metabolic, molecular, and histologic imaging. PAT has the unique strength of high-resolution imaging across the length scales of organelles, cells, tissues, organs, and small-animal organisms with consistent contrast. PAT has the potential to empower holistic omniscale biology research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. Potential applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in both animals and humans.

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Abstract, April 24, 2017
New perspectives on disease diagnosis: From mobile phones to molecular engineering

Daniel A. Fletcher

Early detection of disease remains a major goal of modern healthcare. This talk with describe efforts at two different scales to harness technology for improved healthcare, one centered on converting mobile phones into image-based diagnostic platforms and the other focused on understanding and manipulating molecular mechanisms involved in target recognition by the innate immune system.

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Abstract May 1, 2017
An Integrative Circuit-Host Modeling Framework for Synthetic Biology

Chen Liao

One fundamental challenge in synthetic biology is the lack of quantitative tools that accurately describe and predict the behavior of engineered gene circuits. This challenge arises from many factors, among which the complex interdependence of circuits and their host serves as a leading cause. Here we present a gene circuit modeling framework that explicitly integrates circuit behaviors with host physiology through bidirectional circuit-host coupling. Using Escherichia coli as a model, we first established a coarse-grained but mechanistic description of host physiology involving dynamic resource partitioning. We then characterized multilayered circuit-host coupling, including generic effects associated with load and growth as well as circuit-specific interactions from ppGpp-mediated global regulation and functional impacts of circuit-produced molecules. The host description and interaction characterization, along with a detailed kinetic module of exogenous circuits, constitute our integrative computational framework. To verify this model, we performed a set of simulations of constitutive gene expression under multiple genetic and environmental conditions. Meanwhile, we showed that our model can be used in other bacterial systems with minimal changes. To demonstrate its utility, we applied the framework to examine a growth-modulating feedback circuit whose behavior is qualitatively altered by circuit-host interactions. Using an extended version of the framework, we further systematically revealed circuit behavior across scales from single-cell dynamics to population behaviors and to the emergence of spatial ecology by using a toggle switch as an example.

Compared to existing approaches, our model offers the following advantages: (1) We explicitly acknowledges the ppGpp-mediated transcription regulation, which has been shown to be essential for both host and circuits. (2) We systematically explores both host-to-circuit interactions and circuit-to-host interactions. (3) Our model enables successful interpretation and prediction of a wide spectrum of experimental data, particularly the dynamic responses, from multiple research groups. (4) Our modeling framework is multiscale, ranging from the single-cell level to the population and the spatial ecological levels.

The ultimate goal of synthetic biology is to rapidly create desired phenotypes through rational design and construction of artificial gene circuits. Therefore, by generating the quantitative knowledge of circuit behavior across scales, this work is valuable to the field that is currently suffering from the lack of predictive tools. Meanwhile, by systematically illustrating key host cellular processes and multilayered circuit-host interactions, the work also sheds light on quantitative biology towards a better understanding of complex bacterial physiology. Overall, this work advances our quantitative understanding of gene circuit behavior, benefiting rational design of artificial gene networks and thus expediting the advances of next-generation synthetic biology applications.

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Date Topic Speaker
Monday
9/12/2016
Recent Advances in Clinical MRI

(Abstract)

Jason Polzin, Ph.D.
General Manager, Applications and Workflow, General Electric Healthcare, Global Magnetic Resonance Imaging
Monday
9/19/2016
Tools for engineering personalized neural tissue

(Abstract)

Stephanie Willerth, Ph.D. and P.Eng
Canada Research Chair in Biomedical Engineering, Associate Director of the Center for Biomedical Research, Mechanical Engineering, Division of Medical Sciences
University of Victoria
Monday
9/26/2016
Single Molecule Biosensors for Dynamic Multigene Analysis in Complex Tissue Environments

(Abstract)

Pak Wong, Ph.D.
Professor, Biomedical Engineering, Mechanical Engineering, and Surgery
Pennsylvania State University
Monday
10/3/2016
Microengineered Devices for Cells, Tissues and Organs

(Abstract)

Nancy Allbritton, M.D., Ph.D.
Chair, UNC/NC State Biomedical Engineering, Debreczeny Distinguished Professor of Chemistry, University of North Carolina at Chapel Hill
Monday
10/10/2016
Open Source Image Informatics for Multidimensional Live Cell Imaging

(Abstract)

Kevin Eliceiri
Director, Laboratory for Optical and Computational Instrumentation
UW-Madison, Investigator, Morgridge Institute for Research
Monday
10/17/2016
The Mechanical Environment of Pregnancy

(Abstract)

Kristin M. Myers
Associate Professor, Mechanical Engineering, Columbia University
Monday
10/31/2016
The Blood-Brain Barrier: An obstacle and an opportunity

(Abstract)

Eric Shusta
Howard Curler Distinguished Professor, Chemical & Biological Engineering, UW-Madison
Monday
11/7/2016
Nanofluidic Biochips for Cell Transfection and Regenerative Medicine

(Abstract)

L. James Lee Helen C. Kurtz Chair, Chemical & Biomolecular Engineering, The Ohio State University
Monday
11/14/2016
Therapeutic immunomodulation via rationally designed self-assembled nanomaterials

(Abstract)

Evan A. Scott
Assistant Professor, Biomedical Engineering, Northwestern University
Monday
11/21/2016
Imaging and modeling approaches for ovarian cancer

(Abstract)

Paul Campagnola
Professor, Biomedical Engineering, UW-Madison
Monday
12/05/2016
Big Ten Speaker Exchange Biochemical tools development for precise description of protein function

(Abstract)

Tamara Kinzer-Ursem
Assistant Professor, Biomedical Engineering, Purdue University

 

Abstract, 9/12/2016
Recent Advances in Clinical MRI 

Jason Polzin, Ph.D.

Since the introduction of the first 1.5 Tesla high field imaging systems, the use of Magnetic Resonance for diagnostic imaging has grown significantly to the point where it has become the standard of care for neuro and musculoskeletal diagnostic procedures. At the same time, the technology has experienced rapid growth in body, oncology and cardiac applications. However, primarily due to cost and complexity the availability has been limited in parts of the world. Even in developing markets reimbursement pressures have impacted its adoption reinforcing the need to make MR faster, more robust, and easier to use. This presentation will describe recent advances in Clinical MRI to address that need.

 

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Abstract, 9/19/2016
Tools for engineering personalized neural tissue

Stephanie Willerth, Ph.D. and P.Eng

Treating neurological diseases and disorders accounts for 6.7% of the total attributable cost of illness in Canada. These issues arise when healthy neural tissue stops functioning properly. My research focuses on developing personalized engineered tissues that could successfully provide a long term strategy for treating diseases and disorders of the central nervous system, such as spinal cord injury. We hypothesized that generating spinal motor neurons (sMNs) from human induced pluripotent stem cells (hiPSCs)-derived neural aggregates (NAs) using a chemically-defined differentiation protocol would be more effective inside of 3D fibrin hydrogels compared to 2D laminin-coated surfaces. To test this hypothesis, we performed targeted RNA-Seq using next generation sequencing to determine the substrate-specific genetic differences that regulate cell phenotype. Cells cultured on both substrates expressed sMN genes CHAT and MNX1, though persistent Wnt signaling contributed to a higher proportion of interneurons in NAs cultured in 3D fibrin scaffolds. Cells in fibrin also expressed lower levels of astrocyte progenitor genes and higher levels of the neuronal-specific gene TUBB3, suggesting a purer population of neurons compared to the 2D cultures. This work provides insight into how fibrin hydrogels affect neuronal induction and these insights can then be used to tailor the properties of these hydrogels to optimize sMN generation for regenerative medicine applications.

 

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Abstract, 9/26/2016
Single Molecule Biosensors for Dynamic Multigene Analysis in Complex Tissue Environments 

Pak Wong, Ph.D

Collective cell migration is a fundamental multicellular activity that plays essential roles in numerous physiological and pathological processes, such as angiogenesis, tissue regeneration, and cancer metastasis. Proper coordination of cells, for instance, is required to repair damaged tissues in which cells crawl collectively atop exposed extracellular matrix following injury. The collective migration mechanisms responsible for tissue development are also utilized in the invasion and metastasis of malignant tumors. Despite its importance, the fundamental processes that drive collective cell migration, such as leader cell formation and biomechanical coupling, remain poorly understood. To elucidate the collective migration process, my laboratory is developing molecular and nanoengineering techniques for single molecule imaging, dynamic gene expression analysis, single cell photothermal ablation, biomechanical analysis of cell-cell and cell-matrix interaction, and agent-based computational modeling. In this talk, I will discuss the application of a single cell nanobiosensor for probing the mechanoregulation of collective cell migration. Using the nanobiosensor, we reveal that the formation of leader cells during collective migration is dynamically regulated by Dll4 signaling through both Notch1 and mechanical force. Our finding provides a molecular basis for the stochastic emergence of leader cells, which may enable novel approaches in regenerative medicine, diabetic wound healing and cancer treatment.

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Abstract, 10/3/2016
Microengineered Devices for Cells, Tissues and Organs 

Nancy Allbritton, M.D., Ph.D.

The ability to monitor and manipulate the microenvironment of cells and tissues is one of the most promising applications for microengineered systems. The laboratory is developing a suite of technologies based on microengineered platforms and microfluidics to manipulate and analyze living cells. We have developed simple, inexpensive fabrication methods utilizing photoresists, plastics, and hydrogels for cell-based arrays, organ-on-chips, and tissue scaffolds. The fabricated devices include detachable, deformable, or biodegradable array elements designed for cell analysis and sorting. A second focus area exploits recent advances in mating living cells with microfabricated systems making it possible to create miniaturized devices with organ level function. These “organ-on-a-chip” platforms enable the controlled establishment of multicellular tissue-like cell populations from pluripotent cells.

 

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Abstract, 10/10/2016
Open Source Image Informatics for Multidimensional Live Cell Imaging 

Kevin Eliceiri

Modern Biological imaging now has the unprecedented ability to track biological phenomena in high resolution in physiologically relevant conditions over time and in space. As these imaging technologies mature and become main stream tools for the bench biologist there is great need for improved software tools that drive the informatics workflow of the imaging process from acquisition and image analysis to visualization and dissemination. To best meet the workflow challenges, these tools need to be freely available, open source, and transparent in their development and deployment. Different imaging processing and visualization approaches need access not only to the data but also to each other. There needs to be compatibility not only in file import and export but interoperability in preserving and communicating what was done to the image. We present the efforts towards interoperability in the Fiji and Open Microscopy Environment consortiums that are leveraging new development of ImageJ with the development and utilization of key software libraries like ImgLib, Ops and Bio-Formats to parse and visualize multidimensional biological image data.

 

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Abstract, 10/17/2016
The Mechanical Environment of Pregnancy 

Kristin M. Myers

The reproductive soft tissues that support the fetus undergo some of the most dramatic and unique growth and remodeling events in the human body. During pregnancy, the uterus and fetal membrane must grow and stretch to accommodate the fetus. Simultaneously, the cervix must remodel and be a mechanical barrier to keep the fetus within the uterus. All three tissues must withstand mechanical forces to protect, support, and maintain an optimal growth environment for the developing baby. Then, in a reversal of roles, ideally nearing term, the uterus begins to contract and the cervix deforms to allow for a safe delivery. The magnitude of stress and stretch of these soft tissues supporting the fetus are thought to control physiologic processes that regulate tissue growth, remodeling, contractility, and rupture, and it is generally hypothesized that these mechanical signals are clinical cues for normal labor and preterm birth, a major long-lasting public health problem with heavy emotional and financial consequences. In this talk I will reveal what we know about the soft tissue mechanics of pregnancy. I will present finite element models of pregnancy based on ultrasonic anatomical data, and I will examine the mechanical function of the soft tissues that support the fetus. I will also specifically characterize cervical material properties using a hyperelastic constitutive model that accounts for the cervical collagen fiber architecture and hormone-mediated remodeling relationships. Through this experimental and modeling effort I aim to identify which factor or combination of factors is responsible for clinically-observed mechanical dysfunction in pregnancy.

 

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Abstract, 10/31/2016
The Blood-Brain Barrier: An obstacle and an opportunity 

Eric Shusta

Millions of people worldwide are afflicted with neurological diseases such as Parkinson’s disease, Alzheimer’s disease, brain cancer, and cerebral AIDS. Although many new drugs are being developed to combat these and other brain diseases, few new treatments have made it to the clinic.  The impermeable nature of the brain vasculature, also known as the blood-brain barrier (BBB), is at least partially responsible for the paucity of new brain therapeutics.  As examples, approximately 98% of small molecule pharmaceuticals do not enter the brain after intravenous administration, and the BBB prevents nearly all protein and gene medicines from entering the brain.  Our research group is therefore focused on developing tools for the analysis of the brain drug delivery process and identifying novel strategies for circumventing this transport barrier.  This presentation will detail our recent work regarding the development of stem cell-based in vitro experimental models that accurately mimic the BBB characteristics observed in vivo.  Such models are amenable to drug permeability screening and human disease modeling.  In addition, I will discuss our efforts to overcome BBB restrictions on brain drug delivery. To this end, we are mining large antibody libraries to identify antibodies that can target and act as artificial substrates for endogenous receptor-mediated BBB nutrient transport systems.   After conjugation to drug payloads that can include small molecules, proteins, or DNA therapeutics, these antibodies could have the potential to deliver medicines across the BBB noninvasively.

 

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Abstract, 11/7/2016
Nanofluidic Biochips for Cell Transfection and Regenerative Medicine 

L. James Lee

Nanofluidics based biochips are a major platform technology being developed in our center for next-generation biomedical applications such as cancer cell interrogation and regenerative medicine. It requires strong interdisciplinary collaboration among engineering, science and medicine. Here we show the development of a new technology, nanochannel electroporation (NEP) and its applications in a frontier medical field, Regenerative Medicine. Many transfection techniques can deliver biomolecules into cells, but the dose cannot be controlled precisely. Delivering well-defined amounts of materials into cells is important for various biological studies and therapeutic applications. NEP may deliver precise amounts of a variety of transfection agents into individual living cells. The cell to be transfected is positioned next to a nanochannel. Delivering a voltage pulse across the nanochannel produces an intense electric field over a very small area on the cell membrane, allowing a precise amount of transfection agent to be electrophoretically driven through the nanochannel, the cell membrane and into the cell cytoplasm, without affecting cell viability. Dose control is achieved by adjusting the duration and number of pulses. Both 2D and 3D NEP biochips are successfully used for non-viral generation of induced neurons (iNs), endothelial cells (iECs) and induced pluripotent stem cells (iPSCs) with high efficiency, an important step to realize regenerative medicine. A NEP patch is also developed for skin transfection activated regeneration. Using mouse models, we demonstrated the potential of NEP biochips and NEP patch for future clinical use in stroke recovery and wound healing.

 

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Abstract, 11/14/2016
Therapeutic immunomodulation via rationally designed self-assembled nanomaterials 

Evan A. Scott

Synthetic nanomaterials that are engineered to achieve specific biodistributions and mechanisms of degradation hold great promise for controlled stimulation of the immune system. Through the use of such rationally designed nanomaterials, we aim to investigate the basic inflammatory and immunological processes contributing to diverse pathologies and develop targeted immunotherapies. We specifically approach this by synthesizing, assembling and testing in vitro and in vivo a range of nanostructures loaded with strategically selected combinations of immunostimulants to achieve controlled elicitation or suppression of the immune system. Here, I will present some of our ongoing work in the areas of nanomaterials development, neonatal immunization, and vaccination against tuberculosis.

 

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Abstract, 11/21/2016
Imaging and modeling approaches for ovarian cancer 

Paul Campagnola

 

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Abstract, 12/5/2016
Biochemical tools development for precise description of protein function 

Tamara Kinzer-Ursem

Dr. Kinzer-Ursem’s research includes protein engineering, protein assay and technology development, and computational biology. Her research group is developing selective protein tagging and protein-surface conjugation methods that are coupled with nanotechnologies and other emergent techniques to rapidly isolate and characterize protein function and improve protein assay workflow. These technologies are applied to the study of the spatiotemporal dynamics in protein signaling networks and advancements in the fields of medical diagnostics, and drug discovery and development. This talk will focus on two of our most recent technology developments: a molecular detection technology that is based on the principles of diffusivity and Brownian motion, and the tagging of newly synthesized proteins during specific time windows in juvenile and developing mice.

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Date Topic Speaker
Monday
2/1/2016
Micro Scale Tools Enable Functional and Mechanistic Insights in Cancer
(Abstract)
David Beebe, PhD
John D. MacArthur Professor & Claude Bernard Professor
Biomedical Engineering
UW-Madison
Monday
2/15/2016
The Emergent Collective Behavior of Bacteria Under Stress
(Abstract)
Robert Austin, PhD
Professor
Physics
Princeton University
Monday
2/22/2016
Microwave thermal ablation: Technology development and clinical application
(Abstract)
Christopher Brace, PhD
Associate Professor
Biomedical Engineering & Radiology
UW-Madison
Monday
2/29/2016
Understanding initial stages of carcinogenesis using label-free optical nanoimaging and nanosensing
(Abstract)
Vadim Backman, PhD
Walter Dill Scott Professor
Biomedical Engineering & Program Leader of Cancer and Physical Sciences at the Robert H. Lurie Comprehensive Cancer Center
Northwestern University
Monday
3/7/2016
Big Ten Speaker Exchange
Optical coherence tomography of retinal morphology and physiology
(Abstract)
Xincheng Yao, PhD
Professor
Bioengineering and Ophthalmology & Vision Sciences
University of Illinois at Chicago
Monday
3/14/2016
Uncovering the Behavior of Particles in the Lung by Coupling Numerical Predictions with Experimental Data
(Abstract)
Jessica Oakes, PhD
Presidential Postdoctoral Scholar
Mechanical Engnieering
UC Berkeley
Monday
3/28/2016
Engineering gene networks to program bacteria and their communities
(Abstract)
Ting Lu, PhD
Assistant Professor
Bioengineering
U of Illinois at Urbana–Champaign
Monday
4/4/2016
The Biomedical Engineer at the Bedside: How Engineers have improved the Lives of Neurology Patients
(Abstract)
Elizabeth Felton, MD, PhD
Assistant Professor
Neurology
UW-Madison
Monday
4/11/2016
Big Ten Speaker Exchange
Engineered Lipid Vesicles as Carriers of Therapeutics for Selective Treatment of Untargetable Cancers
(Abstract)
Stravroula Sofou, PhD
Associate Professor
Biomedical Engineering
Rutgers University
Monday
4/18/2016
Osteoarthritis: A Multiscale Mechanics Perspective
(Abstract)
Corrine Henak, PhD
Assistant Professor
Mechanical Engineering
UW-Madison
Monday
4/25/2016
Midwest Graduate Student Speaker Exchange
Development of Novel Nanomedicines for Treatment of Primary and Metastatic Prostate Cancer
(Abstract)
Omer Ayden, University of Michigan

Abstract, 2/1/2016
Micro Scale Tools Enable Functional and Mechanistic Insights in Cancer

David Beebe, Ph.D

The role of cell-cell communication in many aspects of cancer (initiation, progression, resistance) is becoming increasingly apparent. We have developed a number of simple tools to improve our ability to manipulate and probe the nature of these multi cellular interactions both in isolation and in the context of the tumor microenvironment. These include 2D & 3D compartmentalized culture platforms to explore paracrine signaling and matrix interactions as well as lumen-based organotypic models to understand structure/function relationships. In addition, we have developed tools to enable multianalyte extraction from small precious samples from patients. We are applying these tools to understand how cell-cell communication influences various aspects of cancer development in the context of the tumor ecosystem. Examples include the transition from DCIS to IDC in breast cancer, metastasis to bone in prostate cancer, angiogenesis in kidney cancer, hormone response in breast cancer and resistance to therapy in multiple myeloma

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Abstract, 2/15/2016
The Emergent Collective Behavior of Bacteria Under Stress

Robert Austin, PhD

Outside the ivied halls of the academy, Darwinian evolution and competition puts an enormous selection pressure on organisms. Although physicists tend to think of bacteria as being rather simple entities living rather solitary and brief lives, our experience has been that under high stress complex environments and at high concentrations they initiate complex, cryptic signaling and information exchange whose purposes we at this point can only guess at. I’ll present experiments showing the complexity of the signals that bacteria exchange under stress, and try to provide some sort of a model to understand the purposes of this emergent collective behavior.

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Abstract, 2/22/2016
Microwave thermal ablation: Technology development and clinical application

Christopher Brace, PhD

Microwave thermal ablation is a minimally invasive, image-guided technique for treating many cancers. The objective is to heat and destroy cancerous tissue while sparing as much normal tissue as possible. This presentation will briefly outline the clinical need for microwave ablation and describe current technologies. The presentation will also cover technical challenges with solutions in the design of ablation systems, new research and clinical directions, and our experience in the translation of laboratory research to device commercialization and eventual clinical use.

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Abstract, 2/29/2016
Understanding initial stages of carcinogenesis using label-free optical nanoimaging and nanosensing

Vadim Backman, PhD

Initiation of carcinogenesis is accompanied by alterations in tumor microenvironment, cellular metabolism and epigenetics. Understanding these early events depends on our ability to image these subtle nanoarchitectural and functional processes. The talk discusses a suit of novel fiber-optic and in vitro diagnostic optical imaging techniques that have recently been developed to quantify intracellular and tissue morphology at the nanoscale and provide high-resolution imaging of metabolism and microangiography. The techniques have shown promise as a new platform for highly sensitive, cost-effective and non-invasive cancer screening and prognostication. From the clinical perspective, these techniques have shown promise as a new platform for highly sensitive, cost-effective and non-invasive screening and prognostication of lung, colon, and prostate cancers. From the biology perspective, the talk focuses on elucidating the role of higher-order chromatin structure and dynamics as a crucial driver of gene regulation and its dysregulation in many cellular pathological processes including carcinogenesis.

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Abstract, 3/7/2016
Optical coherence tomography of retinal morphology and physiology

Xincheng Yao, PhD

Given the excellent resolution to differentiate individual functional layers, optical coherence tomography (OCT) has increasing applications in retinal disease detection and treatment assessment. Better understanding of anatomic and physiological sources of retinal OCT is essential for accurate interpretation of clinical outcomes. Using custom-designed time-domain and spectral-domain OCTs, we have conducted a series of experiments to characterize the effect of sub-cellar structures such as photoreceptor inner segment (IS) ellipsoids and retinal pigment epithelium (RPE) melanosomes. Moreover, we recently demonstrated functional OCT of transient intrinsic optical signal (IOS) changes correlated with retinal physiological kinetics, and developed multi-modal OCT to enable concurrent IOS imaging of retinal neural activity and angiographic monitoring of vascular hemodynamics.

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Abstract, 3/14/2016
Uncovering the Behavior of Particles in the Lung by Coupling Numerical Predictions with Experimental Data

Jessica Oakes, PhD

Pulmonary diseases cause a substantial medical and financial burden worldwide and are typically caused by inhalation of air pollution or cigarette smoke over a long period of time. Aerosolized medicine is an effective way to treat these diseases, however targeted lung delivery remains a challenge, especially in the presence of disease. Physiologically based computer simulations provide novel insight of lung mechanics, however simulations need validating before they can be translated into clinical settings. In this seminar, I will introduce a novel MRI method to quantify particle deposition in healthy and diseased rat lungs. Next, complementary multi-scale numerical simulations of airflow and particle transport will be discussed. I will then focus on the advantages of coupling simulations with experimental data to provide detailed insight beyond the resolution of the data. At the end of the talk I will discuss the challenge of validating computer models and my perspective on what is required to bring these types of models into medical practices.

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Abstract, 3/28/2016
Engineering gene networks to program bacteria and their communities

Ting Lu, PhD

Gene regulatory networks are one of the major cellular infrastructures that give rise to defined cellular functions. My research focuses on the analysis, construction and utilization of these networks in bacteria for functionality programming. In this talk, I will report our recent efforts in engineering lactic acid bacteria for potential biomedical applications, such as bacteriocin overproduction, as well as in developing synthetic bacterial consortia to understand the structure and dynamics of microbial communities.

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Abstract, 4/4/2016
The Biomedical Engineer at the Bedside: How Engineers have improved the Lives of Neurology Patients
Elizabeth Felton, M.D., PhD

Advances in neuroengineering have helped us understand how to interface with and manipulate the nervous system. However, since much of the research is laboratory based, it can be easy for investigators to lose the forest for the trees. Meaning that one can get so caught up in the minutia of research that it can be difficult to see how and when patients with neurological disorders would actually reap any benefit from the project. In light of this, I will present several examples of how advances in neuroengineering have directly improved, and in some cases lengthened, the lives of neurology patients, specifically those with epilepsy.

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Abstract, 4/11/2016
Engineered Lipid Vesicles as Carriers of Therapeutics for Selective Treatment of Untargetable Cancers

Stravroula Sofou, PhD

We use model lipid membranes in the form of vesicles to study pH-controlled lateral lipid phase separation processes and their effect on altering the vesicles’ surface topography and functionality, the vesicles’ membrane permeability and fusogenicity. We design and study such pH-dependent processes on model functionalized lipid bilayers in the form of giant and of small unilamellar vesicles. Giant lipid vesicles are used as templates to study the morphology, reversibility, and kinetics of formation and growth of phase separated lipid domains. Integration of these processes on nanometer-sized lipid vesicles used as drug delivery carriers may precisely control their interactions with diseased cells increasing therapeutic efficacy while minimizing toxicities.

Two examples of improving the therapeutic potential in liposomal chemotherapy and alpha-particle radiotherapy will be presented: first, the description and demonstration of the efficacy of vesicles with ‘sticky patches’. These vesicles introduce new binding geometries with targeted receptors, and enable selective targeting and effective killing of cancer cells currently reported as untargetable by today’s reported nanoparticles; and second, the description of highly diffusing forms of lethal agents delivered and released within the tumor interstitium, and the demonstration of using this approach to effectively address the low and heterogeneous drug distributions in solid tumors that currently limit the therapeutic efficacy of these agents.

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Abstract, 4/18/2016
Osteoarthritis: A Multiscale Mechanics Perspective

Corrine Henak, PhD

Osteoarthritis (OA), characterized by damage and loss of articular cartilage, is a mechanically-mediated disease with a large economic burden and a negative impact on patients’ quality of life. Abnormal mechanical loading that initiates and advances OA has been quantified at the joint scale. However, OA begins at the tissue scale with microdamage such as fibrillation of the articular surface. Therefore, to fully understand OA, tissue scale mechanics that cause microdamage must be established. This presentation will focus on research quantifying abnormal cartilage mechanics that cause OA across length scales and across joints, with the long-term aim of accurately predicting joint damage and remodeling on a subject-specific basis.

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Abstract, 4/25/2016
Midwest Graduate Student Speaker Exchange
Development of Novel Nanomedicines for Treatment of Primary and Metastatic Prostate Cancer

Omer Ayden

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Date Topic Speaker
Monday
9/21/2015
Corrine Bahr Memorial Lecture
Integration of Systems Biology, Tissue Engineering, and Microdevices for Drug Development
(Abstract)
Linda Griffith, Ph.D.
S.E.T.I. Professor
Dept. of Biological and Mechanical Engineering
Massachusetts Institute of Technology
Monday
9/28/2015
The Impact of Cellular Network and Microenvironmental Variations in Disease
(Abstract)
Pam Kreeger, Ph.D.
Assistant Professor
Dept. Biomedical Engineering
UW-Madison
Monday
10/5/2015
Bioengineering Silk Proteins for Regenerative Medicine
(Abstract)
David Kaplan, Ph.D.
Stern Family Professor of Engineering
Professor and Chair
Dept. of Biomedical Engineering
Tufts University
Monday
10/12/2015
The Role of the Scientist in the Clinic: A Medical Physicist’s Perspective
(Abstract)
Timothy Szczykutowicz, Ph.D.
Assistant Professor
Dept. of Radiology and Medical Physics
UW–Madison
Monday
10/19/2015
Information Intensive Guided Therapy: Moving Beyond Tracking Surgical Devices to Tracking Therapy
(Abstract)
Walter Block, Ph.D.
Professor
Dept. of Medical Physics and Biomedical Engineering
UW–Madison
Monday
11/2/2015
Polymer Coatings for Cell Culture Studies
(Abstract)
Padma Gopalan, Ph.D.
Professor
Dept. of Material Science and Engineering
UW–Madison
Monday
11/9/2015
Engineering Materials for Functional Nerve Regeneration
(Abstract)
Christine Schmidt, Ph.D.
Pruitt Family Professor & Chair
Dept. of Biomedical Engineering
University of Florida
Monday
11/23/2015
Monolayer Elasticity in Collective Cell Migration
(Abstract)
Jacob Notbohm, Ph.D.
Assistant Professor
Dept. of Engineering Physics
UW–Madison
Monday
12/7/2015
Development and validation of MRI-based quantitative imaging biomarkers
(Abstract)
Diego Hernando, Ph.D.
Assistant Scientist
Dept. of Radiology
UW–Madison

Abstract, 9/21/2015
Integration of Systems Biology, Tissue Engineering, and Microdevices for Drug Development

Linda Griffith, Ph.D.

“Mice are not little people” – a refrain becoming louder in the drug development community, as the strengths and weaknesses of rodent models of human disease become more apparent. At the same time, three emerging approaches are headed toward integration: powerful systems biology analysis of cell signaling networks on patient samples; 3D tissue engineered models of human organ systems, often made from stem cells; and microfluidic devices that enable living systems to be sustained and used for models like cancer metastasis. This talk will highlight the integration of these rapidly moving fields to understand difficult clinical problems including cancer metastasis and women’s reproductive health.

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Abstract, 9/28/2015
The Impact of Cellular Network and Microenvironmental Variations in Disease

Pam Kreeger, Ph.D.

Cellular behavior results from the complex interplay between the cell and influences from the surrounding microenvironment (e.g., extracellular matrix, growth factors). Overlaid on this already complex relationship is the reality that different cells (e.g., different cell types, cells from different patients) have variation in their internal cell network that impact processing of these inputs into decisions. To analyze questions about these relationships, my lab utilizes computational modeling and develops biomimetic in vitro models. In this talk, I will discuss our ongoing efforts to use these methods in cancer and wound healing.

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Abstract, 10/5/2015
Bioengineering Silk Proteins for Regenerative Medicine

David Kaplan, Ph.D.

Silk is one of the oldest biomaterials, utilized as sutures and in wound healing for centuries, yet undergoing a rebirth into new biomaterial formats and applications over the past few decades. One key to this emergence has been to modify the native protein using new processing methods and chemistries to engineer new material features. Some of these strategies developed to morph silk, a high molecular weight amphiphilic protein, into new materials with new properties will be discussed. The utility of some of these new material formats in printing, scaffolding and related applications will also be discussed. The needs for tunable, degradable, robust biomaterials for a range of tissue engineering and regenerative medicine goals remains high and silk proteins offer a unique suite of options to help address these needs.

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Abstract, 10/12/2015
The Role of the Scientist in the Clinic: A Medical Physicist’s Perspective

Timothy Szczykutowicz, Ph.D.

A brief overview of imaging and therapy technologies commonly used in radiology and radiation oncology departments across the globe will be given. Then, an overview of the work of the presenter in the area of computed tomography (CT) focusing on current research related to monitoring image quality, CT protocol optimization, and the clinical workflow will be covered. The seminar will cover professional and scientific aspects of the role of a medical physicist in a university hospital setting. The presenter currently mentors multiple UW-Madison BME undergraduates and hopes this seminar will expose more engineering students to the possibilities a future in medical imaging could offer.

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Abstract, 10/19/2015
Information Intensive Guided Therapy: Moving Beyond Tracking Surgical Devices to Tracking Therapy

Walter Block, Ph.D.

The brunt of image-guidance used in surgery today is still provided by co-registering anatomical images from pre-operative diagnostic imaging with the geometric space of the operating room. This approach is somewhat akin to printing out turn by turn driving directions before you leave the house. You will have a good idea of where you are going, but traffic, accidents, and state troopers will still surprise you. This seminar will sow how real-time imaging during surgical procedures can provide information that not only tracks devices, but allows interventionists to quantitatively track treatments precisely as they are administered. Applications in cancer therapy, gene therapy, and stem cell delivery will be shown.

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Abstract, 11/2/2015
Polymer Coatings for Cell Culture Studies

Padma Gopalan, Ph.D.

Chemically defined synthetic surfaces play an important role in understanding stem cell behavior. We have developed a chemically defined ultra-thin coatings that is stable over timeframes relevant to differentiation of hMSCs. The coating consists of a copolymer, which incorporates orthogonal chemistry for the crosslinking and peptide binding. The orthogonal chemistry allows for (i) substrate adaptability, (ii) scalability over large areas, (ii) absolute quantification of peptides, (iv) chemically defined passage of hMSCs, (v) stability of peptide-polymer bonds, and (vi) long-term coating stability. This coating platform can potentially elucidate cell-material interactions in vitro and have far-reaching effects on stem cell culture methods. I will specifically talk about how recent advances in materials science characterization tools such a X-ray photoelectron spectroscopy (XPS) can be leveraged for precise quantification of these soft templates.

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Abstract, 11/9/2015
Engineering Materials for Functional Nerve Regeneration

Christine Schmidt, Ph.D.

Damage to spinal cord and peripheral nerve tissue can have a devastating impact on the quality of life for individuals suffering from nerve injuries. Our research is focused on analyzing and designing biomaterials that can interface with neurons and specifically stimulate and guide nerves to regenerate. These biomaterials might be required for facial and hand reconstruction or in trauma cases, and potentially could be used to aid the regeneration of damaged spinal cord.

New technologies to aid nerve regeneration will ultimately require that biomaterials be designed both to physically support tissue growth as well as to elicit desired receptor-specific responses from particular cell types. One way of achieving such interactive biomaterials is with the use of natural-based biomaterials that interact favorable with the body. In particular, our research has focused on developing advanced hyaluronan-based scaffolds that can be used for peripheral and spinal nerve regeneration applications. Hyaluronic acid (HA; also known as hyaluronan) is a non-sulfated, high molecular weight, glycosaminoglycan found in all mammals and is a major component of the extracellular matrix in the nervous system. HA has been shown to play a significant role during embryonic development, extracellular matrix homeostasis, and, most importantly for our purposes, in wound healing and tissue regeneration. HA is a versatile biomaterial that has been used in a number of applications including tissue engineering scaffolds, clinical therapies, and drug delivery devices. Our group has devised novel techniques to process this sugar material into forms that can be used in therapeutic applications. For example, we are using advanced laser-based processes to create “lines” of specific proteins within the hyaluronan materials to provide physical and chemical guidance features for the individual re-growing axons. We have found that these materials facilitate neuron interactions and are thus highly promising for regenerating peripheral and spinal nerves in vivo.

In a parallel approach to foster nerve regeneration, our group has developed natural tissue scaffolds termed “acellular tissue grafts” created by chemical processing of normal intact nerve tissue. These grafts are created from natural biological tissue — human cadaver nerves — and are chemically processed so that they do not cause an immune response and are therefore not rejected in patients. These grafts have been optimized to maintain the natural intricate architecture of the nerve pathways, and thus, they are ideal for promoting the re-growth of damaged axons across lesions. These engineered, biological nerve grafts are currently used in the clinic for peripheral nerve injuries and are being explored for spinal cord regeneration.

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Abstract, 11/23/2015
Monolayer Elasticity in Collective Cell Migration

Jacob Notbohm, Ph.D.

Monolayers of collectively migrating cells are a common model system for studying wound healing, embryonic development and cancer metastasis. The cooperative motions are assumed to be driven by active forces applied by each cell, but there is still no known relationship to connect the forces to the flow of the cellular collective. This talk will describe a spring-like elastic relationship between force and motion within the monolayer. It will be demonstrated how the elasticity can generate emergent phenomena, such as collective waves of cellular motion that propagate across the monolayer.

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Abstract, 12/7/2015
Development and validation of MRI-based quantitative imaging biomarkers

Diego Hernando, Ph.D.

The ability to use imaging to quantify relevant physical parameters (ie: quantitative imaging biomarkers) has the potential to enable improved diagnosis and treatment monitoring of multiple diseases. However, development and validation of quantitative imaging techniques present important challenges beyond those of traditional qualitative imaging. These challenges often include: increased imaging time, ill-posed estimation problems, and unwanted signal contributions due to the presence of multiple confounding factors. In order to overcome these challenges, engineering solutions are needed, which encompass both signal acquisition and image reconstruction. Further, quantitative imaging biomarkers should be accurate, precise, robust and reproducible, and comprehensive validation is required in order to translate these techniques into clinical use. In this seminar, I will describe recent efforts undertaken in collaboration with several Departments at UW-Madison to develop and validate MRI-based quantitative imaging biomarkers. This research seminar will focus on MRI techniques to quantify fat and iron concentration in tissue, including their applications, recent developments, and remaining open questions.

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Date Topic Speaker
Monday
1/26/2015
Optical nanosensors for biological discovery
(Abstract)
Heather Clark, PhD
Associate Professor
Dept. of Pharmaceutical Sciences
Northeastern University
Monday
2/2/2015
Fiber recruitment by cells drives extracellular matrix mechanosensing in engineered fibrillar microenvironments
(Abstract)
Brendon Baker, PhD
Post-doctoral Fellow
Dept. of Biomedical Engineering
Boston University
Monday
2/9/2015
Cell signaling by extracellular matrix stiffness
(Abstract)
Yong Bae, PhD
American Heart Association Postdoctoral Fellow
Dept. of Pharmacology, School of Medicine
University of Pennsylvania
Monday
2/16/2015
Skeletal muscle: history-dependent force production and tissue engineering at the single-fiber level
(Abstract)
David Corr, PhD
Associate Professor
Dept. of Biomedical Engineering
Rensselaer Polytechnic Institute
Monday
2/23/2015
An all human microphysiologic liver system for carcinoma metastasis
(Abstract)
Alan Wells, MD, DMSc
Vice-Chair and Thomas J Gill III Professor
Dept. of Pathology
University of Pittsburgh Medical Center
Monday
3/2/2015
Big Ten Speaker Exchange
Multiplex biomaterials for high throughput cancer drug screening
(Abstract)
Jennifer Leight, PhD
Assistant Professor
Dept. of Biomedical Engineering
The Ohio State University
Monday
3/9/2015
Modular multi-scale modeling of cardiovascular function to probe the etiology of complex cardiovascular disease
(Abstract)
Daniel A. Beard, PhD
Carl J. Wiggers Collegiate Professor of Cardiovascular Physiology
Molecular and Integrative Physiology
University of Michigan
Monday
3/16/2015
The biomedical entrepreneur
(Abstract)
Dennis Bahr, PhD, PE
Vice President of R&D
HelionX, LLC
Monday
3/23/2015
Biomaterials as Therapeutic Cancer Vaccines
(Abstract)
David Mooney, PhD
Robert P. Pinkas Family Professor of Bioengineering
School of Engineering and Applied Sciences, and Wyss Institute
Harvard University
Monday
4/13/2015
Bioengineering of direct cellular reprogramming
(Abstract)
Kam Leong, PhD
Samuel Y. Sheng Professor
Dept. of Biomedical Engineering
Columbia University
Monday
4/20/2015
An in vivo systems biology approach to understanding and treating tuberculosis
(Abstract)
Jennifer Linderman, PhD
Professor of Chemical Engineering
Associate Dean for Graduate Education, College of Engineering
Associate Director, ADVANCE Program
University of Michigan
Monday
4/27/2015
Lymphatic vessels in inflammation and cancer: Linking mechanobiology with

immune regulation
(Abstract)

Melody Swartz
William B. Ogden Professor in Molecular Engineering
University of Chicago
Monday
5/4/2015
Midwest Graduate Speaker Exchange
Adaption of neural control for a powered lower limb prosthesis
(Abstract)
John Spanias
Dept. of Biomedical Engineering
Northwestern University

Abstract, 1/26/2015
Optical nanosensors for biological discovery

Heather Clark, PhD

We have developed an array of fluorescent nanosensors for the measurement of ion and small molecule concentrations in biological environments. Each sensor is based on a polymeric platform that is easily tunable and extendable to new analytes, such as sodium, lithium, glucose, and neurotransmitters. In addition to creating novel probes, we are focused on the application of these nanosensors to solving biological problems. One interest area is the development of an entire Chem-7 “tattoo” for physiological monitoring in the skin. In addition, we are using nanosensors for monitoring neurotransmitter release in neural tissue slices. Ultimately, by combining advanced imaging techniques with our array of nanosensors, we plan to image chemical dynamics at a greater depth in vivo.

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Abstract, 2/2/2015
Fiber recruitment by cells drives extracellular matrix mechanosensing in engineered fibrillar microenvironments

Brendon Baker, PhD

To investigate how cells sense stiffness in settings relevant to the architecture of native extracellular matrices (ECM), we designed a synthetic fibrous material with tunable mechanics and user-defined architecture. In contrast to flat hydrogels, these fibrous materials recapitulated cell-matrix interactions of collagen matrices including arborized cell morphologies, cell-mediated realignment of ECM fibers, and bulk contraction of the material. Surprisingly, while increasing stiffness induced cell spreading and proliferation on flat hydrogels, higher stiffness in fibrous matrices instead suppressed spreading and proliferation. Lower stiffness in fibrous networks permitted active cellular forces to recruit nearby fibers, dynamically increasing ligand density and stiffness local to the cell and promoting the formation of focal adhesions and related signaling. These studies demonstrate a departure from the well-described relationship between material stiffness and spreading established by flat hydrogel surfaces, and introduce fiber recruitment as a novel mechanism by which cells probe and respond to mechanics in fibrillar matrices.

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Abstract, 2/9/2015
Cell signaling by extracellular matrix stiffness

Yong Bae, PhD

Extracellular matrix (ECM) stiffness is transduced into intracellular stiffness, signaling, and changes in cellular behavior. Integrins and several of their associated focal adhesion proteins have been implicated in sensing ECM stiffness. We investigated how an initial sensing event is translated into intracellular stiffness and a biologically interpretable signal. We found that a pathway consisting of focal adhesion kinase (FAK), the adaptor protein p130Cas (Cas), and the guanosine triphosphatase Rac selectively transduced ECM stiffness into stable intracellular stiffness, increased abundance of the cell cycle protein cyclin D1, and promoted S phase entry. Our findings establish that mechanotransduction by a FAK-Cas-Rac signaling module converts the external information encoded by ECM stiffness into stable intracellular stiffness and mechanosensitive cell cycling.

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Abstract, 2/16/2015
Skeletal muscle: history-dependent force production and tissue engineering at the single-fiber level

David Corr, PhD

This seminar will highlight the development and application of two new experimental techniques central to the Corr Lab’s skeletal muscle research: (a) the Drosophila “jump muscle” experimental model and its genetic mutations, and (b) a scaffold-free method to engineer single fibers.

The TDT, or “jump muscle”, of the Drosophila Melanogaster (common fruit fly) is an insect muscle that exhibits both history-dependence and mechanical behavior similar to that observed in mammalian skeletal muscle. The genetic mutability of Drosophila enables precise exchanges of the wild type myosin with either faster (IFI), or slower (EMB) myosin isoforms. Such exchanges can identify how different contractile protein isoforms affect the kinetics and biomechanical function at the single-fiber level, and provide unprecedented insight into the underlying mechanisms of history-dependent behavior, such as force enhancement and force depression.

Time permitting, Dr. Corr will briefly discuss his lab’s scaffold-free approach to engineer single fibers using directed cellular self-assembly to harness the cells’ natural abilities to organize, create extracellular matrix, and form fibers. Cellular growth is guided using novel differentially-adherent growth channels, and a custom electromechanical bioreactor precisely delivers prescribed mechanical strain, electrical stimulation, and soluble factors to these channels. Thus, stimuli can be applied to cells as the fiber forms, thereby providing insight to the influence of the magnitude and timing of environmental cues on fiber development.

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Abstract, 2/23/2015
An all human microphysiologic liver system for carcinoma metastasis

Alan Wells, MD, DMSc

Metastases kill patients, but disseminated cancers are resistant to therapies. The tumor biological events behind this are unknown due to lack of relevant model systems. Further, humans metabolize agents and present toxicities uniquely, hampering drug development. We have developed an all-human microphysiological system of the liver to study both tumor behavior in the common metastatic site, and drug metabolism/efficacy in the main metabolizing organ.

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Abstract, 3/5/2015
Big Ten Speaker exchange
Multiplex biomaterials for high throughput cancer drug screening

Jennifer Leight, PhD

The screening of candidate compounds for potential cancer treatments typically begins with in vitro assays, where cancer cells cultured on tissue culture plastic are treated and cell function is assessed. To “pass” this round of screening, drug treatment must significantly decrease cell number, through induction of cell death or inhibition of proliferation. This approach, however, does not account for effects of the cellular microenvironment on drug responsiveness and does not capture effects of the drug on other cell functions, such as matrix metalloproteinase (MMP) activity, which could have serious implications for cancer progression and metastasis. To overcome this barrier, we have developed a functionalized hydrogel cell culture platform that enables simultaneous measurement of cell viability and MMP activity in a physiologically relevant 3D microenvironment. Here we present use of this platform to investigate how pharmacological inhibition of the protein kinase signaling cascade (RAS-BRAF-MEK-ERK) affects melanoma cell function.

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Abstract, 3/9/2015
Modular multi-scale modeling of cardiovascular function to probe the etiology of complex cardiovascular disease

Daniel A. Beard, PhD

It is increasingly recognized that multifactorial diseases arise from interaction between genetic and environmental factors, and physiological systems. Examples of particular relevance to human health include the major health burdens that we face: cardiovascular disease and heart failure; metabolic syndrome and type 2 diabetes; and cancer. In all of these examples, acute and chronic (mal)adaptions of specific molecular mechanism and pathways in disease states occur against a background of physiological regulation. Since processes involved in complex disease operate in the context of physiological regulatory mechanisms, an understanding of a disease process builds upon an understanding of the associated physiological systems.

The Virtual Physiological Rat (VPR) is a multi-national research program combining model-driven experiments and experimentally validated multi-scale models to develop theoretical and computational framework explaining: (1.) the long-term regulation of arterial pressure; and (2.) the etiology and sequelae of hypertensive heart disease, spanning molecular genetic to whole-body function. Recent results elucidating novel hypotheses for the mechanisms underlying primary hypertension and the role of metabolic alterations in heart failure will we presented.

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Abstract, 3/16/2015
The biomedical entrepreneur

Dennis Bahr, PhD, PE

The job of the entrepreneur is to come up with a solution that can save lives, save money, or produce a better solution that is more precise and/or accurate. I will discuss some of the dos and don’ts for an entrepreneur and spend the rest of the time discussing how to find the significant problems that need to be solved and how to develop the solution to solve these problems (“how to think out of the box”). I will use examples from my own work including, intracranial pressure monitoring, narrow band auscultatory blood pressure measurement, and a signal extraction method called the Period Transform.

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Abstract, 3/23/2015
Biomaterials as Therapeutic Cancer Vaccines

David Mooney, PhD

Therapeutic cancer vaccines typically depend on extensive manipulation of cells in the laboratory, but subsequent cell infusion typically leads to large-scale cell death and limited efficacy. We are instead developing biomaterials that provide controlled delivery of immunomodulatory factors, in certain ways mimicking aspects of microbial infection, to target immune cells in the body and bypass the need to manipulate cells in the laboratory. These material strategies allow control over immune cell trafficking and activation, promote potent responses to cancer antigens, and cause tumor regression in preclinical models.

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Abstract, 4/13/2015
Bioengineering of direct cellular reprogramming
Kam Leong, PhD

Transdifferentiation, or direct cell reprogramming, where differentiated cells are reprogrammed into another lineage without going through an intermediate stem cell-like stage, produces cells promising for regenerative medicine. It obviates the use of embryos and minimizes the risk of teratoma formation associated with the use of induced pluripotent stem cells. To facilitate eventual translation of transdifferentiation technologies we have demonstrated the feasibility of converting fibroblasts into neurons by nonviral overexpression of transcription factors. The poor conversion efficiency of nonviral direct cell reprogramming requires improvement. I will discuss our effort on optimizing the biochemical and physical cues to enhance neuronal transdifferentiation. In particular, I will highlight the role of topographical substrates in modulating the purity, conversion kinetics, and subtypes of the induced neurons generated by direct reprogramming. I will also discuss our recent effort on using CRISPR/dCas9 gene activation approach to achieve direct cellular reprogramming.

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Abstract, 4/20/2015
An in vivo systems biology approach to understanding and treating tuberculosis

Jennifer Linderman, PhD

Approximately one third of the world’s population is infected with Mycobacterium tuberculosis. Limited information about how the immune system fights M. tuberculosis and what constitutes protection from the bacteria impact our ability to develop effective therapies for tuberculosis. Our approach integrates data from multiple model systems and over multiple length and time scales into a comprehensive multi-scale and multi-compartment view of the in vivo immune response to M. tuberculosis. I will describe computational models that we use to explore the ‘design space’ of potential disease therapies.

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Abstract, 4/27/2015
Lymphatic vessels in inflammation and cancer: Linking mechanobiology with immune regulation

Melody Swartz

In tissues, interstitial fluid flow is mechanically coupled to lymphatic drainage, and both are often increased in acute inflammation as well as in the tumor microenvironment where steeper-than-normal pressure gradients exist at the tumor margin due to higher fluid pressure in tumors. It has long been assumed that local lymph formation is driven primarily by pressure gradients generated by downstream lymphatic pump function, but we have found that vesicular transendothelial transport also contributes significantly to lymph formation and is actively regulated by the lymphatic endothelium according to inflammatory stimuli, allowing fine-tuning of the transport of antigens, cells, and chemokines to the local lymph node. But why does lymphatic transport need to be actively regulated, if its primary function is to merely drain excess fluid from the interstitium to prevent swelling? In exploring this question, we are finding lymphatic transport to play fundamental roles in fine-tuning immune responses and regulating the presentation of abundant self-antigens for deletion of autoreactive T cells. At the same time, inflammatory lymphangiogenesis coupled with increased interstitial flow drives fibroblast activation and stromal changes that promote matrix alignment and stiffening as well as, simultaneously, immune suppression. In the tumor microenvironment, these factors synergize to promote escape from host immunity, which is presumably necessary for metastasis. Together, these findings help to define new immunomodulatory roles for lymphatic vessels in inflammation and cancer.

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Abstract, 5/4/2015
Midwest Graduate Speaker Exchange
John Spanias

Adaption of neural control for a powered lower limb prosthesis

Powered leg prostheses are driven by motors and are capable of restoring important functional tasks such as stair climbing by generating positive mechanical work at the knee and ankle joints. They are typically programmed with different modes (e.g., level walking, stair ascent). We have developed a pattern recognition system for a powered knee-ankle prosthesis that uses information from EMG and embedded mechanical sensors to transition the leg into the desired mode seamlessly and automatically. Our studies have shown that EMG information complements mechanical sensor information, and significantly reduces the error rates of the pattern recognition system. However, variations in EMG signals, such as those due to electrode shift, can decrease system accuracy. We have developed an adaptive pattern recognition system that can automatically adjust system parameters based on new EMG information and maintain high prediction accuracy. Our system uses a statistical threshold based on the EMG training data to detect detrimental changes in EMG information and prevent the errors associated with them. Our system also features a novel supervision method that uses the leg’s mechanical sensors to accurately label new data with the correct mode. We have completed an offline analysis evaluating the performance of the system across experimental sessions, when electrode shift is expected because of donning and doffing the device. Our analysis has shown that the adaptive system not only prevent errors caused by changes in EMG signals, but also learns from this new information to decrease the error rate with each step of the amputee.

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Date Topic Speaker
Monday
9/8/2014
Biomimetic nanofibrous structures direct stem cell differentiation for connective tissue generation
(Abstract)
Wan-Ju Li, Ph.D.
Assistant Professor
Depts. of Orthopedics and Rehabilitation, Biomedical Engineering
UW-Madison
Monday
9/15/2014
The importance of intellectual property: a patent primer and overview of WARF
(Abstract)
Brian Frushour, MS
Intellectual Property Associate
Wisconsin Alumni Research Foundation
Monday
9/29/2014
The “unified airway disease”: asthma and obstructive sleep apnea—an evolving translational journey.
(Abstract)
Mihaela Teodorescu, MD
Associate Professor
Div. of Pulmonary and Critical Care
UW School of Medicine and Public Health
Monday
10/6/2014
Seeds, soils, stem cells, and cancer
(Abstract)
Shelly Peyton, Ph.D.
Assistant Professor
Dept. of Chemical Engineering
University of Massachusetts, Amherst
Monday
10/13/2014
Corrine Bahr Memorial Lecture
Bioreactor-based and encapsulated mesenchymal stem cell therapy for protection and repair of injured vital organs and tissues
(Abstract)
Martin L. Yarmush, M.D., Ph.D.
Professor
Depts. of Biomedical & Chemical Engineering
Rutgers University
Center for Engineering in Medicine, MGH/Harvard Medical School
Monday
10/20/2014
Central nervous system stereotactic radiosurgery: technological development opportunities
(Abstract)
Edward T. Bender, PhD, DABR
Assistant Professor
Dept of Human Oncology
UW-Madison,
School of Medicine and Public Health
Monday
10/27/2014
Supramolecular peptide immunomodulators
(Abstract)
Joel Collier, Ph.D.
Associate Professor
Dept. of Surgery – Committee on Molecular Medicine, Committee on Immunology
University of Chicago
Monday
11/3/2014
Bioactive materials for transitioning macrophage and fibroblast phenotypes within chronic vocal fold scar
(Abstract)
Susan Thibeault, PhD, CCC-SLP
Professor
Division of Otolaryngology-Head & Neck Surgery
UW School of Medicine and Public Health
Monday
11/17/2014
Modeling liver disease and development with human iPSCs
(Abstract)
Stephen A. Duncan DPhil
Prof. and Vice-Chairman
Dept. of Cell Biology, Neurobiology & Anatomy
Medical College of Wisconsin
Monday
12/1/2014
Listening to small molecule cellular signaling with micrometabolomics
(Abstract)
Ashleigh Theberge, Ph.D.
Post-doctoral associate
Microtechnology Medicine and Biology Lab
UW-Madison
Monday
12/8/2014
Synthetic Human Tissues for Regenerative Medicine
(Abstract)
Kelly R. Stevens, Ph.D.
Research Scientist
Laboratory for Multiscale Regenerative Technologies
Institute for Medical Engineering and Science
Harvard – MIT Health Science and Technology

Abstract, 9/8/2014
Biomimetic nanofibrous structures direct stem cell differentiation for connective tissue generation

Wan-Ju Li, Ph.D.

Connective tissues, such tendon and intervertebral disc, have tissue-specific extracellular matrix (ECM) structures that are known to play a crucial role in determining their mechanical properties. Recently, it has been reported that ECM structure is able to direct lineage-specific differentiation of stem cells. My research aims to generate functional musculoskeletal tissues using stem cells for orthopedic applications. In this talk, I would like to present our recent findings in 1) using nanofiber technology to fabricate novel engineered nanofibrous matrix to mimic the ECM structures of tendon and intervertebral disc as well as 2) demonstrating how the unique biomimetic structures direct stem cells to differentiate into cell-specific lineages.

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Abstract, 9/15/2014
The importance of intellectual property: a patent primer and overview of WARF

Brian Frushour, MS

Intellectual property (IP) and technology transfer are key drivers of innovation in both industry and academia. The different forms of IP rights will be discussed, with a particular focus on patents. An overview of WARF’s role in technology transfer at UW-Madison will also be covered, including its history and the disclosure process.

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Abstract, 9/29/2014
The “unified airway disease”: asthma and obstructive sleep apnea-an evolving translational journey.

Mihaela Teodorescu, MD

Accumulating literature supports a bidirectional relationship of asthma with obstructive sleep apnea (OSA): OSA is more common in asthma where in turn worsens outcomes. This talk will review the clinical data supporting this reciprocal interaction and expand into its mechanistic underpinnings emerging from recent animal studies. Further research directions will also be outlined.

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Abstract, 10/6/2014
Seeds, soils, stem cells, and cancer

Shelly Peyton, Ph.D.

Metastasis is the leading cause of fatality for women diagnosed with breast cancer. The most common anatomical sites of distant tumor growth include the brain, lung, liver, and bone, and it is well known that metastatic spread in breast cancer is not random. Rather, different clinical subtypes of breast cancer exhibit unique patterns of metastatic site preference, called tissue tropism. I will talk about my lab’s hypothesis that there is a relationship between the biophysical and biochemical properties of the tissue, and the ability of cells within a particular subtype of breast cancer to adhere, migrate, grow, and respond to chemotherapeutics at these secondary sites. I propose that the types of biomaterial environments my lab creates to study these phenomena can be used to predict tissue-specific spread, and may serve as a system that pharmaceutical companies can use for future drug discovery.

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Abstract, 10/13/2014
Bioreactor-based and encapsulated mesenchymal stem cell therapy for protection and repair of injured vital organs and tissues

Martin L. Yarmush, M.D., Ph.D.

Recently there has been a paradigm shift in what is considered to be the therapeutic promise of mesenchymal stem cells (MSCs) in diseases of vital organs. Originally, research focused on MSCs as a source of regenerative cells through the differentiation of transplanted cells into lost cell types. It is now clear, however, that trophic modulation of inflammation, cell death, fibrosis, and tissue repair are primary mechanisms of MSC therapy. This has been clarified in studies where delivery of growth factors, cytokines, and other signaling molecules secreted by MSCs is often sufficient to obtain the therapeutic effects. In this presentation, we provide several examples of MSC therapy in disease models of vital organs using models of acute liver failure, acute kidney failure, and spinal cord injury. Some critical gaps in our knowledge hampering experimental progress and clinical implementation will be discussed.
Corrine Bahr Memorial Lecture

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Abstract, 10/20/2014
Central nervous system stereotactic radiosurgery: technological development opportunities

Edward T. Bender, PhD, DABR

Stereotactic radiosurgery is a non-invasive alternative to surgery for some patients with cancerous and non-cancerous diseases of the central nervous system. Many of the core technologies used for this treatment technique have not changed substantially over the last 45 years. This talk will explore current and future opportunities for radiosurgery technology development, and highlight some of the unique resources UW-Madison has to offer in this endeavor.

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Abstract, 10/27/2014
Supramolecular peptide immunomodulators

Joel Collier, Ph.D.

This talk will discuss self-assembled peptide and protein biomaterials for raising therapeutic immune responses. Projects dealing with designing adjuvant-free vaccines and immunotherapies for chronic inflammation will be described. These materials are designed in a modular style, allowing various immune phenotypes to be specifically targeted.

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Abstract, 11/3/2014
Bioactive materials for transitioning macrophage and fibroblast phenotypes within chronic vocal fold scar

Susan Thibeault, PhD, CCC-SLP

Vocal fold scarring is a debilitation condition that has proven difficult to treat with current surgical techniques or standard injectable fillers. The long term aim of our work is to engineer injectable products that promote wound repair and induce tissue regeneration to treat chronic vocal fold scarring and other extracellular matrix (ECM) defects of the lamina propria. Using PEGDA cytokine hydrogels previously identified as anti-fibrotic and/or immunomodulatory, we will harness the capacity of implanted materials to modulate the phenotype of invading macrophages and vocal fold fibroblasts toward achieving improved restoration of chronic vocal fold scar.

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Abstract, 11/17/2014
Modeling liver disease and development with human iPSCs
Stephen A. Duncan, DPhil

We have previously described a procedure for the efficient differentiation of human iPSCs to cells that display hepatocyte characteristics. Here we report the use of such a system to model inborn errors of hepatic metabolism and to understand the molecule basis of hepatocyte differentiation.

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Abstract, 12/1/2014
Listening to small molecule cellular signaling with micrometabolomics

Ashleigh Theberge, Ph.D.

Small molecule signals provide a rich vocabulary for cellular communication across kingdoms – from bacteria and fungi to mammalian cells. While methods to query expression of proteins and nucleic acids in cell culture systems are well developed, small molecules remain elusive to identify and study. These barriers are principally explained by (1) the sensitivity of small molecule production to culture environments requiring the use of primary cells and physiologically relevant culture systems and (2) the lack of efficient sample preparation platforms to interface culture models with analytical chemistry tools such as mass spectrometry. We have developed a new type of microfluidic systems, called “suspended microfluidics”, that allows biphasic flows in a microdevice controlled by simple pipettes. These novel systems enable the creation of microscale platforms for cell culture that integrate small molecule extraction for downstream metabolomic analysis and accommodate the culture of multiple cell types in connected microfabricated compartments. We have also engineered functional readouts, such as assays for blood vessel formation, into our microculture models, enabling us to establish links between metabolomic profiles and biological function. These microfluidic models show great potential for disentangling complex relationships among cell types – in both normal and disease states – and understanding the chemistry responsible for these interactions.

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Abstract, 12/8/2014
Synthetic Human Tissues for Regenerative Medicine

Kelly R. Stevens, Ph.D.

Human development – the process by which a single celled zygote transforms into a human being – involves the incredibly complex and self-orchestrated specification, differentiation, and assembly of trillions of cells. Despite nature’s power during development, the adult body cannot always reassemble or repair itself after injury, such as after a heart attack or liver cirrhosis. My research seeks to hijack and rewire aspects of nature’s developmental programs in order to control the processes by which communities of cells assemble to form human systems. To do this, I use diverse tools taken from stem cell biology, tissue engineering, synthetic biology, micro/nanofabrication, and bioprinting. Here I will highlight some of my work in both constructing and controlling artificial tissue using both nature’s blueprints and new engineering technologies. This will be in done in the context of developing therapies for organ regeneration and pathogen infection.

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Date Topic Speaker
Monday
1/27/14
Optical imaging of oxygen metabolism
(Abstract)
Cosponsored by LOCI and Prairie Technologies
Hao Zhang, Ph.D.
Associate Professor
Dept. of Biomedical Engineering
Northwestern University
Monday
2/3/14
Ethical implications of the Big Data revolution on research subject privacy
(Abstract)
Ty Harkness
IRES Fellow
Dept. of Biomedical Engineering
University of Wisconsin-Madison
Monday
2/10/14
Single virus bioimaging in pursuit of pre-symptomatic disease diagnosis
(Abstract)
Cosponsored by Optical Society of America
Bennett Goldberg, Ph.D.
Professor
Department of Physics
Boston University
Monday
2/17/14
Sensory responses in the motor cortex and their implications for brain-machine interfaces
(Abstract)
Aaron Suminski, Ph.D.
Research Associate
(Assistant Professor)
Dept. of Organismal Biology and Anatomy
University of Chicago
Monday
2/24/14
Many facets of transducin in photoreceptor signaling and pathology
(Abstract)
Ekaterina Lobanova, Ph.D.
Senior Research Scientist
Alberts Eye Research Center
Duke University Medical School
Wednesday
2/26/14
A Single Peptide-MHC Triggers Digital Cytokine Secretion in CD4+ T Cells
(Abstract)
Jun Huang, Ph.D.
Dept. of Microbiology and Immunology
Howard Hughes Medical Institute
Stanford University
Monday
3/3/14
Elucidating principles of biological signal processing using microfluidic and optogenetic tools
(Abstract)
Megan McClean, Ph.D.
Lewis-Sigler Fellow
Princeton University
Monday
3/10/14
Lung development on a chip: transmural pressure
as a mechanicalregulator of lung branching morphogenesis
(Abstract)
Jason Gleghorn, Ph.D.
School of Engineering and Applied Science
Princeton University
Monday
11/11/2013
TBA
(Abstract)
TBA
Monday
3/24/14
Modeling and analysis of age-dependent microtubule dynamics
(Abstract)
Melissa K. Gardner, Ph.D.
McKnight Land-Grant Professor
Dept. of Genetics, Cell Biology and Development
University of Minnesota
Monday
3/31/14
Micro-platforms to engineer small tissues for regeneration and 3D organ model – liver, pancreas and brain
(Abstract)
SangHoon Lee, Ph.D.
Dept. of Biomedical Engineering
Korea University
Monday
4/7/14
Programmable materials for drug delivery and regenerative medicine
(Abstract)
Yong Wang, Ph.D.
Associate Professor
Dept. of Biomedical Engineering
Penn State University
Monday
4/14/14
Phenotypes and exome sequencing for mutation screening: vision and hearing loss
(Abstract)
Terry Braun, Ph.D.
Associate Professor
Department of Biomedical Engineering
University of Iowa
Monday
4/21/14
Graduate Student Exchange
Engineered Tissues for the Delivery of Cells to Injured Myocardium
(Abstract)
Jacqueline Wendel
Stem Cell Biology Trainee
Dept. of Biomedical Engineering
University of Minnesota – Twin Cities
Monday
4/28/14
Spectral computed tomography: adding a new dimension to CT imaging using photon-counting detectors
(Abstract)
Cosponsored by LOCI and Prairie Technologies
Taly Gilat-Schmidt, Ph.D.
Assistant Professor
Dept. of Biomedical Engineering
Marquette University
Monday
5/5/14
Corrine Bahr Memorial Lecture
University Distinguished Lecture

Engineering microenvironments to regulate forces, form, and multicellular function
(Abstract)
NOTE: Change of location 1610 Engineering Hall
Christopher Chen, Ph.D.
Professor
Dept. of Biomedical Engineering
Boston University

Abstract, 1/27/14
Optical imaging of oxygen metabolism

Hao Zhang, Ph.D.

Oxygen metabolism is a fundamental physiological parameter that is needed to better understand the pathological alterations in many life-threating diseases including diabetic complications and cancers. We developed novel optical imaging technologies (optical coherence tomography and photoacoustic microscopy) that can measure hemoglobin oxygen saturation and blood flow in microcirculations to quantify changes in oxygen metabolism. In this seminar, I will explain our technologies and algorithms with an application to ophthalmology. I will also brief other recent technology developments in our lab.
Cosponsored by LOCI and Prairie Technologies

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Abstract, 2/3/14
Ethical implications of the Big Data revolution on research subject privacy

Ty Harkness

Informed consent has been an integral part of research subject protection since the early 1980s. However, in the context of large biomedical databases driven by electronic health records, “omics” technology, biobanks, and mobile self-tracking data, obtaining informed consent for each desired research application can be difficult or impossible. Growing segments of the health care, drug development, and basic research communities have argued that if the Big Data revolution is to reach its full potential,a loosening of the requirement for informed consent must occur. Balancing research subject autonomy with the potential for large scientific advances for the public good will be a key debate in the evolution of Big Data and will be discussed in this seminar.

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Abstract, 2/10/14
Single virus bioimaging in pursuit of pre-symptomatic disease diagnosis

Bennett Goldberg, Ph.D.

For the history of mankind the treatment of disease has been limited by the simple fact that diagnosis and treatment follow the appearance of symptoms. While we do administer prophylactics in cases of known exposure and high risk, and recommend regular check-ups to identify onset of illness based on genomic analysis and epidemiologically determined environmental risk factors, the question still remains – how would medicine change if pre-symptomatic diagnosis were commonplace? From the simplest perspective, drugs work better when applied earlier in infection and could in some cases be replaced by immune system adjuvants. More interesting would be the capability of pre-symptomatic determination of an unknown infection state, for example during the 2003 SARS coronavirus or 2009 Influenza outbreaks, or after a biothreat.
To address the challenge, we have developed a platform capable of detecting single nanoparticles and viruses with high throughput, no amplification and at low cost. Interferometric, multi-color imaging on simple substrates provides the ability to rapidly scan and identify size, shape, orientation and material properties of single nanoparticles and viruses. To detect and size pathogens, our Interferometric Reflectance Imaging Sensor (IRIS) shines light from multi-color LED sources sequentially on viruses and nanoparticles bound to the sensor surface, which consists of a silicon dioxide layer atop of a silicon substrate. Interference of light reflected from the sensor surface is modified by the presence of particles producing a distinct signal that reveals the size of the particle. The dielectric layered structure acts as an optical antenna optimizing the elastic scattering characteristics improving sensitivity, detection and analysis. We have successfully detected 35 nm and 50 nm radius particles and H1N1 viruses (illustrated in the conceptual picture, right) with accurate size discrimination. We have demonstrated identification of virus particles in complex samples for replication-competent wild-type vesicular stomatitis virus (VSV), defective VSV, and Ebola- and Marburg mimics with high sensitivity and specificity. Size discrimination of the virions allows differentiation between modified viruses having different genome lengths and facilitates a reduction in the counting of non-specifically bound particles to achieve a limit-of-detection (LOD) of 5×103 pfu/mL for the Ebola and Marburg VSV pseudotypes. We also demonstrated the simultaneous detection of multiple viruses in a single sample (composed of serum or whole blood) for screening applications and uncompromised detection capabilities in samples contaminated with high levels of bacteria.
Cosponsored by Optical Society of America

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Abstract, 2/17/14
Sensory responses in the motor cortex and their implications for brain-machine interfaces

Aaron Suminski, Ph.D.

The brain typically utilizes a rich supply of feedback from multiple sensory modalities to control movement. Brain-machine interfaces (BMI) offer the promise of recovered functionality to individuals suffering from severe motor dysfunction by recording movement commands directly from the patient’s primary motor cortex (MI) and rerouting them to an external device, such as a computer cursor or a prosthetic arm. Most current BMI implantations depend solely on visual feedback for closed-loop control; thereby neglecting other potentially beneficial feedback modalities. In this talk, I will describe recent experimental evidence demonstrating strong visual and somatosensory influences on the activity of MI neurons and discuss the usefulness of these sensory-like responses in brain-machine interface training and control. Furthermore, I will show that the control of a cursor driven by the activity of neural ensembles in MI is significantly improved when visual and somatosensory information about the cursor position is available to the BMI user. These findings demonstrate two important facts. First, that the term ‘motor’ cortex conceals the unmistakable sensory-like responses of neurons in the
precentral gyrus. Second, they demonstrate the need for augmenting cortically-controlled BMIs with multiple forms of natural or surrogate sensory feedback.

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Abstract, 2/24/14
Many facets of transducin in photoreceptor signaling and pathology

Ekaterina Lobanova, Ph.D.

Transducin is a heterotrimeric G protein which plays a key role in producing an electrical response to light by photoreceptor cells. Daytime illumination causes massive translocation of transducin from the light-sensitive outer segment to other cellular compartments of rod photoreceptor cells. This process is thought to be vitally important for rods, as it is believed to contribute to both light adaptation and neuroprotection of these cells. I will first describe the molecular mechanism which controls light-evoked transducin translocation and explain why transducin does not translocate in cone photoreceptors. In the second part of my talk, I will demonstrate that the knockout of transducin’s gamma subunit in rods leads to an increased burden on the cellular protein folding and degradation machinery, overloads the capacity of proteasomes to process their unfolded protein substrates and ultimately causes photoreceptor cell death. Finally, I will show that a similar proteasomal overload takes place in photoreceptors of other mutant mice and represents a new common stress factor in multiple forms of retinal degeneration.

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Abstract, 2/26/14
A Single Peptide-MHC Triggers Digital Cytokine Secretion in CD4+ T Cells

Jun Huang, Ph.D.

We have developed a single-molecule imaging technique that uses quantum-dot-labeled peptide-major histocompatibility complex (pMHC) ligands to study CD4+ T cell functional sensitivity. We found that naive T cells, T cell blasts, and memory T cells could all be triggered by a single pMHC to secrete tumor necrosis factor alpha (TNF-a) and interleukin-2 (IL-2) cytokines with a rate of ∼1,000, ∼10,000, and ∼10,000 molecules/min, respectively, and that additional pMHCs did not augment secretion, indicating a digital response pattern. We also found that a single pMHC localized to the immunological synapse induced the slow formation of a long-lasting T cell receptor (TCR) cluster, consistent with a serial engagement mechanism. These data show that scaling up CD4+ T cell cytokine responses involves increasingly efficient T cell recruitment rather than greater cytokine production per cell.

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Abstract, 3/3/14
Elucidating principles of biological signal processing using microfluidic and optogenetic tools

Megan McClean, Ph.D.

Biological networks, like electrical circuits, take specific inputs (nutrient availability, stress, hormones) and convert them into appropriate outputs (transcriptional responses, metabolic remodeling). Electrical engineers uncover the inner workings of such circuits by measuring the transfer function between input voltage and output voltage. However, unlike electrical engineers, biologists are more limited in the input signals they can generate to interrogate such networks. We are developing microfluidic and optogenetic tools to generate dynamic inputs to interrogate and control natural and synthetic biological networks. In this talk I will discuss our use of microfluidics to dissect the mechanisms and kinetics of signaling in stress response networks in the budding yeast Saccharomyces cerevisiae. In addition, I will discuss our recent efforts to develop real-time optogenetic control of protein concentration as a tool for manipulating biological networks.

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Abstract, 3/10/14
Lung development on a chip: transmural pressure as a mechanical

regulator of lung branching morphogenesis
Jason Gleghorn, Ph.D.

Branching morphogenesis is a developmental program used by many organs, including the lung, kidney, prostate, and mammary gland, to create ramified networks of epithelial tubes that support the flow of fluid and air. Development of the lung is dynamic, highly regulated, and stereotyped, leading to an airway architecture that is conserved within a given species and critical for survival. Interestingly, although the architecture of the airways is optimized for efficient conduction of air, development occurs with a fluid-filled lumen. Whereas almost all contemporary studies focus on the molecular and genetic programs active during branching morphogenesis of the lung, clinical observations and large animal models suggest a critical role for the (dynamic) regulation of mechanical forces, e.g. transmural pressure, in the developing lung. To investigate the role of transmural pressure in branching morphogenesis, I discuss the development of a microfluidic device to culture and apply dynamically-controlled transmural pressures within murine embryonic whole lung explants. This new approach permits the branching process to be imaged dynamically at multiple length scales under defined mechanical conditions over days of organ development. Using this microfluidic device along with newly developed measurement techniques and quantitative frameworks to describe the airway architecture, I discuss how lumenal fluid flows, generated by pressure-dependent airway smooth muscle contractions, drive branching morphogenesis. Together, my results demonstrate a novel physical mechanism through which lung branching morphogenesis is mechanically regulated in normal development. These studies 1) suggest that lumenal fluid forces may be critical for sculpting the airway architecture, ultimately leading to enhanced convection of air through the mature airway tree and 2) point to additional studies to determine how mechanical forces integrate into the molecular and genetic programs that control morphogenetic processes in developing tissues.

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Abstract, 3/24/14
Modeling and analysis of age-dependent microtubule dynamics

Melissa K. Gardner, Ph.D.

Microtubules are key structural and transport filaments inside of cells. The dynamics at microtubule ends are characterized by periods of slow growth, followed by stochastic switching events termed “catastrophes”, in which microtubules suddenly undergo rapid shortening. The mechanistic basis of catastrophe is not known. To investigate microtubule catastrophe events, we performed 3D mechanochemical simulations that account for interactions between neighboring protofilaments, and then tested our modeling predictions using Total Internal Reflection Fluorescence (TIRF) and Electron microscopy of microtubules. We found that the likelihood of a catastrophe event may be intimately linked to the aging physical structure of the growing microtubule tip. These results have important consequences for catastrophe regulation in cells, as microtubule-associated proteins could promote catastrophe events in part by modifying microtubule tip structures.

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Abstract, 3/31/14
Micro-platforms to engineer small tissues for regeneration and 3D organ model – liver, pancreas and brain

SangHoon Lee, Ph.D.

Uniform sized and well-organized 3D tissue model is important in drug screening, stem cell differentiation, regenerative medicine and analysis of cellular behavior study in tissue. However, the controlled creation of 3-D ultra-structures for 3D tissue model and its culturing under the physical and chemical stimuli mimicking in vivo environment has been a great challenge. In this presentation, we developed several efficient methods to produce
3D tissue model having uniform cell size, shape and functions using microscale arrayed concave PDMS wells. The concave wells were fabricated by two simple and cost effective methods’ the one is by the deflection of thin PDMS membrane and its replication with UV curable materials, and the other is by creating meniscus of viscose PDMS observed that the a few hundreds micron-scale concave structure prevents the cell adherent and enhance cell aggregation. Using this property, we successfully produced following 3D tissues: 1), rat hepatocyte spheroid and hetero-spheroid including hepatocyte and hepatic stellate cell, even with vascular structure, and human hepatocyte spheroid co-cultured with human adipose stem cells, and proved its application of ready-to- use xenogenic bioartificial liver 2) islet spheroid production and in situ encapsulation for glucose control of mouse, and 3), neuron spheroid for brain study including amyloid-beta effect on 3D neurons. Finally, the new fibers which were coded with different chemicals or morphologies were fabricated using the microfluidic chip combined with computer controlled arrayed valve system. Combining this coded fiber with cell spheroid, the 3D organ model was achieved for the immune-protected artificial islet.

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Abstract, 4/7/14
Programmable materials for drug delivery and regenerative medicine
Yong Wang, Ph.D.

The inappropriate delivery of drugs, particularly protein drugs, will cause severe toxicity and low therapeutic efficacy. We are interested in developing a programmable material that can deliver multiple protein drugs at the right time at the right dose for the right duration, and applying this material to tissue regeneration.

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Abstract, 4/14/14
Phenotypes and exome sequencing for mutation screening: vision and hearing loss

Terry Braun, Ph.D.

The speed and cost of next-generation sequencing has improved to the point of allowing exome sequencing for clinical genetic testing. The problem still remains of assessing pathogenicity of potentially thousands of variations from mutation screening efforts. Disease phenotypes can be used to guide the mutation screening and pathogenicity assessment process. I will describe phenotypic-based screening efforts for vision (Leber’s congenital amaurosis) and hearing loss.

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Abstract, 4/21/14
Engineered Tissues for the Delivery of Cells to Injured Myocardium

Jacqueline Wendel

Cellular therapy post-infarction has become an attractive solution to the high incidence of heart failure that results without treatment. However, many current approaches to cell delivery result in poor cell engraftment and limited functional benefits. Engineered cardiac tissue patches have emerged as a means to both deliver and retain large numbers of cells near the site of infarction, maximizing the beneficial capacity of the entrapped cells. This work covers the development, optimization and characterization of an aligned, fibrin-based, stretch-conditioned cardiac patch, and also its capacity to limit left ventricular (LV) remodeling in the acute phase post-infarction. Cardiac patches were constructed from native (CM+) and cardiomyocyte-depleted (CM-) neonatal rat heart cell populations entrapped in a fibrin gel. Contractile force generation of patches increased over two-fold when exposed to cyclic stretching, and were sensitive to stretch amplitude but not duration. Stretch-conditioned patches were sutured onto the LV epicardium of syngeneic, immunocompetent rats immediately after ligation of the LAD coronary artery. Prior to implantation, the ECM of both patches remained primarily fibrin but entrapped cells had begun to deposit ECM proteins, with increased collagen deposition occurring in CM+ patches. CM+ patches generated measurable contractile forces (2.5±0.8mN) both spontaneously and in response to pacing. Vascular structures were found inside the patch after 3 days in vivo. After 4 weeks in vivo, the patches had been remodeled into a collagenous tissue and live, elongated donor cardiomyocytes were found within the engrafted CM+ patches. Non-cardiomyocyte cell migration from the CM+ patch into the host myocardium was found after both 1 and 4 weeks in vivo. Significant improvement in cardiac contractile function was seen with the administration of the CM+ patch (EF 35.1±4.0% for MI only, 58.8±7.3% with a CM+ patch) associated with a 77% reduction in infarct size (61.3±7.9% for MI only, 13.9±10.8% for CM+ patch), and the elimination of LV free wall thinning.. Decreased infarct size and reduced wall thinning also occurred with the administration of the CM- patch (infarct size 36.9±10.2%, LV wall thickness: 1058.2±135.4μm for CM- patch, 661.3±37.4μm for MI only), but without improvements in cardiac function. No benefits were seen with the administration of a decellularized patch. Improvements in contractile function and the substantial reduction of infarct size are likely a result of paracrine effects, due to the separation of donor CMs from the host myocardium and thin dimension of the patches. These beneficial effects seen in a patch containing CMs indicate the effects are dependent upon cellular communication between cardiomyocytes and non-myocyte cardiac cells. Current work is focused on development and characterization of a similar patch utilizing human iPS-cell derived cardiomyocytes to be delivered to the injured myocardium postinfarction.

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Abstract, 4/28/14
Spectral computed tomography: adding a new dimension to CT imaging using photon-counting detectors

Taly Gilat-Schmidt, Ph.D.

New x-ray detectors capture information about the energy of detected photons. This detected spectral information can be used to differentiate materials based on composition, which has shown promise for improved imaging of contrast agents. The spectral information can also improve the quality of conventional CT images. However, spectral CT is currently limited by nonideal detector effects. This talk will present an overview of spectral CT imaging, as well as our work in overcoming the limitations of photon-counting detectors to realize the benefits of spectral CT.
Cosponsored by LOCI and Prairie Technologies

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Abstract, 5/5/14
Corrine Bahr Memorial Lecture
University Distinguished Lecture
Engineering microenvironments to regulate forces, form, and multicellular function

Christopher Chen, Ph.D.

A long recognized tenet of biological systems is that structure gives rise to function. Mechanical force in contrast has emerged only recently as a critical dimension that links form and function, providing the central effector to sculpt the body plan during morphogenesis, as well as a mechanism for cells to sense and respond to local changes in tissue structure and mechanics. Despite the realization that forces, form, and function permeate all living systems, we as a research community sorely lack methods to control the mechanics of the environment, the spatial organization of cells, or the architecture of cell-matrix and cell-cell interfaces, which collectively define the boundary conditions for how forces are transmitted into cells. Here, I will describe our efforts to design and build physical microenvironments that explicitly manipulate and monitor the structure and mechanics of cellular interactions with their surroundings, and how we have used these approaches to gain insights into their role in regulating cell and tissue structure, signaling, and function. I will use our studies to illustrate 1) the multiple means by which cell-material interactions can control cell signaling and function; 2) the importance of novel engineering and materials approaches to understanding cellular decision making; and 3) opportunities and challenges for how to connect these insights to the ultimate translational objectives set by regenerative medicine.

 

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Date Topic Speaker
Monday
9/16/2013
Biomaterial platforms to explore cancer and
stem cell engineering (Abstract)
Brendan Harley, Ph.D. Assistant Professor
Dept. of Chemical and Biomolecular Engineering
Univ. of Illinois Urbana-Champaign
Monday
9/23/2013
Thrombospondins and Ocular Vascular Homeostasis (Abstract) Nader Sheibani, Ph.D. Associate Professor RRF/
Alice R. McPherson Chair
Dept. of Ophthalmology & Visual Sciences, UW-Madison
Monday
9/30/2013
Value added: Biomechanical simulation advances understanding of upper limb function (Abstract) Wendy Murray, Ph.D. Associate Professor
Dept. of Biomedical Engineering and Physical Medicine and Rehabilitation
Northwestern Universtiy
Monday
10/7/2013
Design and Evaluation of Biomaterials for Engineering Vascularized Tissues (Abstract) Eric Brey, Ph.D. Professor
Dept. of Biomedical Engineering
Illinois Institute of Technology
Monday
10/21/2013
Tumor ablation at the University of Wisconsin-A minimally invasive paradigm for the treatment of cancer (Abstract) Fred T. Lee Jr, M.D. Professor
Dept. of Radiology
UW School of Medicine and Public Health
Thursday 10/24/2013
4:00 pm
Speech Responses in the
Auditory Midbrain: A Novel
Hypothesis for Vowel Coding (Abstract) Women in Science & Engineering Leadership Institute (WISELI) Seminar Note change of location and time: 140 Bardeen (4pm)
Laurel Carney, Ph.D. Professor
Dept. of Biomedical Engineering
Dept. of Neurobiology & Anatomy
University of Rochester
Monday
10/28/2013
Translating High-Resolution Label-Free Optical Imaging Technologies into Medical and Surgical Applications (Abstract) Stephen Boppart, M.D., Ph.D. Abel Bliss Professor of Engineering
Dept. of Electrical and Computer Engineering
Univ. of Illinois Urbana-Champaign
Tuesday
11/12/2013
3:00pm
Imaging the Molecular Mechanisms Underlying Insulin Secretion (Abstract) Note change of day and time Cosponsored by LOCI and Prairie Technologies David Piston, Ph.D. Professor
Dept. of Molecular Physiology and Biophysics
Vanderbilt University
Monday
11/18/2013
Top-down modulation of auditory processing in the mouse midbrain and thalamus (Abstract) Cosponsored by LOCI and Prairie Technologies Daniel A. Llano, Ph.D. Assistant Professor in Molecular and Integrative Physiology and the College of Medicine
Univ. of Illinois Urbana-Champaign
Monday
11/25/2013
Regenerative biomaterials: clinical impact today and ideas for tomorrow (Abstract) Note change of location: Wisconsin Institutes for Discovery (WID)Forum,
330 N. Orchard Street
Cosponsored by the Lectures Committee and WID
Jennifer Elisseeff, Ph.D. Jules Stein Professor
Dept. of Biomedical Engineering
Johns Hopkins University
Monday
12/2/2013
Quantitative Second-Harmonic Generation Microscopy (Abstract) Cosponsored by LOCI and Prairie Technologies Kimani C. Toussaint, Ph.D. Associate Professor
Mechanical Science and Engineering
Univ. of Illinois Urbana-Champaign

Abstract, 9/16/13
Biomaterial platforms to explore cancer and stem cell engineering
Brendan Harley, Ph.D.

The extracellular matrix (ECM) is a complex organization of structural proteins such as collagens and proteoglycans. Heterogeneous tissues with spatially and temporally modulated properties and their biomaterial mimics play an important role in organism physiology and regenerative medicine. With the understanding that the microstructure, mechanics, and composition of the ECM is dynamic and often spatially patterned or heterogeneous over the length-scale of traditional biomaterials, there has recently been significant effort aimed at moving away from static, monolithic biomaterials towards instructive biomaterials that provide specialized cell behavioral cues in spatially and temporally defined manners. I will describe the development of instructive biomaterial systems to explore the practical significance of how cell/matrix cues can be optimized to improve regenerative potential and the mechanistic details of how individual (stem) cells sense, integrate, and respond to multiple microenvironmental signals. We are using these approaches to design biomaterial platforms to investigate fundamental questions regarding niche-mediated regulation of hematopoietic stem cell (HSC) behavior, to explore synergistic action between local biophysical/biochemical properties for orthopedic interface repair, and to examine the impact of microenvironmental signals on glioma malignancy and therapy.

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Abstract, 9/23/13
Thrombospondins and Ocular Vascular Homeostasis
Nader Sheibani, Ph.D.

We are interested in how angiogenesis is normally regulated, and how alterations in these regulatory mechanisms lead to neovascularization associated with various pathologies. We use wild type and various trangenic mice in relevant models of ocular neovascularization. In addition, we have developed a novel method for culturing various vascular cell types from wild type and transgenic mouse retina. These cells allow us to examine cell autonomous regulatory mechanisms involved in regulation of vascular development and neovascularization. These in vivo and in vitro models are also utilized for drug screening and development of new therapeutics for various ocular diseases with a neovascular component.

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Abstract, 9/30/2013
Value added: Biomechanical simulation advances understanding of upper limb function
Wendy Murray, Ph.D.

The aim of my research is to use biomechanics as a framework for investigating how we move and control our arms and hands. In my lab, biomechanical modeling and simulation serve as methodological tools that advance the types of questions we can ask about upper limb function. In this talk, I will highlight examples in which biomechanical simulation added important insights that would have been difficult (or impossible) to derive from experiments. In doing so, I will illustrate significant contributions computer simulations methods have made to our understanding of the musculoskeletal design and function of the human upper limb at the basic, translational, and clinical levels.

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Abstract, 10/7/13
Design and Evaluation of Biomaterials for Engineering Vascularized Tissues 
Eric Brey, Ph.D.

Vascularization is critical for engineering tissues of clinical size. Successful vascularization requires the design, optimization and evaluation of the physical and chemical properties of biomaterials used as tissue engineering scaffolds. In this presentation, biomaterial techniques developed to vascularize tissues of clinically relevant size and structure will be described. In addition, the application of X-ray phase contrast for the evaluation of engineered tissues will be presented.

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Abstract, 10/21/13
Tumor ablation at the University of Wisconsin-A minimally invasive paradigm for the treatment of cancer
Fred T. Lee Jr, M.D.

Image-guided minimally invasive tumor ablation is increasingly being used to treat tumors in the liver, lung, kidneys, and bone. However, the technology of tumor ablation remains in its infancy, often lagging behind the progress made in other cancer treatments such as chemotherapy, radiation, and advanced surgical techniques. The multidisciplinary UW Tumor Ablation Laboratory has contributed several new technologies that are currently in clinical use. This seminar will discuss the history of tumor ablation, clinical uses of the different devices, and current areas of research.

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Abstract, 10/24/13
Speech Responses in the Auditory Midbrain: A Novel Hypothesis for Vowel Coding
Laurel Carney, Ph.D.

We combine neurophysiological, behavioral, and computational modeling techniques towards our goal of understanding neural mechanisms underlying the perception of complex sounds. Most of our work is focused on hearing in listeners with normal hearing ability. We are also interested in applying the results from our laboratory to the design of physiologically based signal-processing strategies to aid listeners with hearing loss.

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Abstract, 10/28/13
Translating High-Resolution Label-Free Optical Imaging Technologies into Medical and Surgical Applications
Stephen Boppart, M.D., Ph.D.

Historically, histopathological observations of fixed and stained tissue sections made using bright-field light microscopes in the pathology Dept. have represented the gold-standard for diagnosing most diseases. Essential for diagnosis is the ability to visualize the microscopic cellular and tissue architecture, as well as potential molecular alterations using special immunohistochemical stains. New high-resolution optical imaging technologies capable of providing microscopic structural, molecular, or functional information about tissue, in real-time, and at the point-of-care, would provide innumerable benefits for disease screening, early detection, and more rapid diagnosis across a wide range of medical and surgical specialties. Recent advances in label-free optical imaging technologies now make it possible to provide these capabilities and information, and importantly, do so without the use of exogenous contrast agents that can often limit translation because of regulatory hurdles. This seminar will present several examples of label-free optical biomedical imaging technologies including optical coherence tomography, multi-photon microscopy, and coherent anti-Stokes Raman scattering microscopy, all of which are at varying stages of clinical translation into human studies and commercial development. Current challenges in optical source development, system engineering, and clinical adoption will also be discussed.

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Abstract, 11/12/13 (Note, date is a Tuesday)
Imaging the Molecular Mechanisms Underlying Insulin Secretion
David Piston, Ph.D.

It has long been known that only a small fraction (<10‰) of the insulin in pancreatic beta-cells can be released. Clinical treatments of type 2 diabetes focus on increasing insulin release, so an understanding of insulin vesicle trafficking and release may lead to novel therapeutic strategies. Towards this understanding, we have developed novel quantitative imaging assays, based on Förster resonance energy transfer (FRET), a technique widely used to study biomolecular dynamics and protein interactions in live cells. Limitations due to brightness differences, donor:acceptor stoichiometry, and cross-talk between the donor and acceptor can lead to misleading or even meaningless results. I will present two methods that we have developed to help alleviate these problems with cellular FRET measurements. The first approach for absolute and high precision measurements of FRET efficiency is based upon the use of an optical switching acceptor. By employing a defined train of optical perturbations to control the on and off states of the acceptor, it is possible to modulate the fluorescence intensity of the donor, and this can be analyzed using a lock-in detection approach. The second approach is to use spectral imaging with a newly developed snapshot hyperspectral imager – Image Mapping Spectrometer (IMS). The IMS allows the whole X, Y, Z datacube to be captured in a single snapshot, and optical throughput is maximized.
Cosponsored by LOCI and Prairie Technologies

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Abstract, 11/18/13
Top-down modulation of auditory processing in the mouse midbrain and thalamus
Daniel A. Llano, Ph.D.

The neural mechanisms responsible for using high-level contextual cues to shape lower-level sensory processing are not yet known. An ideal substrate for this type of processing is the massive top-down projection system emanating from virtually every level of the auditory system. Our laboratory uses a range of optical, physiological, computational and anatomical techniques to study top-down projections from the cortex to two major subcortical regions: the auditory thalamus and the inferior colliculus. Using these approaches, we have found that the auditory corticocollicular projection system consists of at least two different subsystems, one emanating from cortical layer 5 and another emanating from layer 6, and that these projection systems have different physiological and anatomical features. We have also assessed cortical influences on the thalamus by way of studying the influence of the thalamic reticular nucleus on colliculo-thalamocortical transmission. To do this, we have developed a computational model of this system and used flavoprotein autofluoresence imaging to develop and study a novel mouse brain slice preparation containing intact projections from the inferior colliculus to the thalamus and from thalamus to cortex. Both in the model and in the brain slice preparation, we have observed that the thalamic reticular nucleus, under certain conditions, causes paradoxical enhancement in thalamocortical transmission. These data point to the wealth of previously uncharacterized complexity found in the descending systems that shape responses to real-world sounds.

Cosponsored by LOCI and Prairie Technologies

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Abstract, 11/25/13
Regenerative biomaterials: clinical impact today and ideas for tomorrow
Jennifer Elisseeff, Ph.D.

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Abstract, 12/2/2013
Quantitative Second-Harmonic Generation Microscopy
Kimani C. Toussaint, Ph.D.

Advances in nonlinear microscopy, e.g., multiphoton fluorescence microscopy and second-harmonic generation (SHG) microscopy, have permitted both noninvasive and high-resolution imaging of biological specimens. In recent years, there has been increasing effort to use these techniques to perform quantitative inspection of specimens under study. This talk will focus on two particular techniques: Fourier transform-second-harmonic generation (FT-SHG) and polarization-second-harmonic generation (P-SHG) and their potential biomedical applications.

Cosponsored by LOCI and Prairie Technologies

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Date Topic Speaker
Monday
1/28/2013
From the Dynamics of Sand to the Dynamics of Robots: Using Advanced
Computing in Virtual Prototyping for Better Engineering Designs (Abstract)
Prof. Dan Negrut Director, Wisconsin Applied Computer Center
Dept. of Mechanical Engineering
Dept. of Electrical and Computer Engineering
UW – Madison
Monday
2/18/2013
Hilldale Distinguished Lecturer Simple building blocks of complex biological systems (Abstract) Prof. Uri Alon Weizmann Institute of Science
Rehovot, Israel
Monday
2/25/2013
Hypofractionated Radiotherapy and the Real Issue: Oxygen Dynamics (Abstract) Prof. Michael Kissick Medical Physics, Human
Oncology, and
affiliated with the Morgridge Institute for Research
UW-Madison
Monday
3/4/2013
University Distinguished Lecturer MR-guided interventions and thermal therapy (Abstract) Prof. Jason Stafford Dept. of Biomedical Engineering
University of Texas Health Sciences Center and MD Anderson Cancer Center, Houston, TX
Monday
3/11/2013
Computational models to investigate anti-angiogenic cancer therapies targeting the
VEGF pathway (Abstract)
Dr. Stacey Finley Postdoctoral Fellow under Prof. Popel, Dept. of Biomedical Engineering, School of MedicineJohns Hopkins University
Monday
3/18/2013
Novel pathways for cardiac matrix assembly (Abstract) Cosponsored by LOCI and Prairie Technologies Prof. Alissa Weaver School of Medicine,
Vanderbilt University
Nashville, TN
Monday
4/15/2013
Systems analysis of TGF-beta signaling dynamics (Abstract) Sponsored by UWCCC Prof. Xuedong Liu Dept. of Chemistry and Biochemistry
University of Colorado, Boulder
Monday
4/22/2013
Glucose effects on endothelial cell mechanotransduction (Abstract) Prof. Alisa Morss Clyne Dept. of Mechanical Engineering
Drexel University,
Philadelphia, PA
Monday
4/29/2013
Big Ten Speaker The importance of multiscale mechanics in tissue engineering and mechanobiology (Abstract) Prof. Ed Sander Dept. of Biomedical Engineering
University of Iowa,
Iowa City, Iowa
Monday
5/6/2013
Continuing professional development in an academic medical center: a maintenance of quality issue (Abstract) Prof. Carla Pugh Dept. of Surgery
UW-Madison

Abstract, 1/28/2013
From the Dynamics of Sand to the Dynamics of Robots: Using Advanced
Computing in Virtual Prototyping for Better Engineering Designs
Prof. Dan Negrut

This talk outlines a high performance computing-enabled software
infrastructure aimed at supporting physics-based simulation for virtual
prototyping purposes. The motivation for building this infrastructure is a
desire to understand and shape the role that advanced computing can play in
Computer Aided Engineering over the next decade. The applications we take
upon are related to granular dynamics, rigid/flexible many-body dynamics,
and fluid-solid interaction problems. CHRONO, the software infrastructure
developed as part of this ongoing effort, partitions the problem of interest
into a number of sub-problems that are solved in parallel using Graphics
Processing Unit (GPU) cards, or multi-core CPUs. The five components at the
cornerstone of the vision that eventually led to CHRONO are: (a) modeling
support for multi-physics phenomena; (b) scalable numerical methods for
multi-GPU and multi-core hardware architectures; (c) methods for proximity
computation and collision detection; (d) support for domain decomposition
and load balance; and (e) tools for carrying out visualization and
post-processing in a distributed manner. Several engineering applications
will be used to demonstrate how these five components are implemented to
leverage a heterogeneous CPU/GPU cluster. The talk will conclude with a
brief discussion of current trends in high performance computing and how
they are poised to change the field of Computational Science in the near
future.

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Abstract, 2/18/2013
Simple building blocks of complex biological systems
Prof. Uri Alon

To understand biological systems, our lab has defined “network motifs”: basic interaction patterns that recur throughout biological networks, much more often than expected at random. The same small set of network motifs appears to serve as the building blocks of the circuitry that processes information from bacteria to mammals. Specific network motifs may be universal building blocks of biological computation. We experimentally studied the function of each network motif in the bacterium E. coli using dynamic fluorescent measurements from living cells. Each network motif can serve as an elementary circuit with a defined function: filters, pulse generators, response accelerators, temporal-pattern generators and more. Evolution seems to have rediscovered the same motifs again and again, perhaps because they are the simplest and most robust circuits that perform these information-processing functions.

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Abstract, 2/25/2013
Hypofractionated Radiotherapy and the Real Issue: Oxygen Dynamics
Prof. Michael Kissick

Radiation therapy goes all the way back to Mme. Curie. The main
physics-related advances are reaching the point of diminishing returns.
Being able to sculpt the beam and adjust it for motion are now so advanced
that sparing the normal tissue around a tumor is nearly optimal from a
physics/geometrical standpoint. Breaking the treatment up into many
“fractions” to integrate damage in the tumor while allowing normal tissue to
repair may not be as needed as before. If that is the case, the effects of
oxygen dynamics can become much more challenging. In these hypofractionated
treatments expected to be more common in the future, we will need to monitor
and adapt to oxygen transients much better than we do now. I believe
optical technologies can play a key role.

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Abstract, 3/4/2013
MR-guided interventions and thermal therapy
Prof. Jason Stafford

The unique soft-tissue contrast and functional imaging capabilities make MRI an attractive modality for planning, targeting, monitoring and verifying successful completion of diagnostic and therapeutic interventions.Image-guidance of minimally invasive interventions for diagnosis and therapy has been a rapidly evolving, multidisciplinary field, particularly with respect to incorporation of increasing advanced imaging equipment for the planning, targeting, monitoring and assessment of procedures. Traditionally, these vascular, therapeutic and biopsy procedures have been carried out using fluoroscopy, ultrasound or CT. MRI is an inherently 3D, non-ionizing imaging modality offering multiple soft-tissue contrast mechanisms as well as functional imaging in a single locale. Because of these unique properties, use of MRI for guidance of interventions has been of growing interest in recent years for a number of procedures requiring stereotactic localization and planning or real-time image guidance and monitoring, such as biopsy and thermal therapy delivery.

However, despite the recent proliferation of commercially available hardware and software solutions for MR guided procedures, integration of MRI into an intraoperative and interventional environment remains a challenge. Because of the cost associated with equipment acquisition and siting, careful attention should be paid to specifying the MR system as well as the location of the facility. The specification of hardware and software, as well as the layout of the suite, strongly influence workflow and domain of possible procedures that can be realistically performed in the suite. Last, but certainly not least, the safety of patients and staff working in the MR environment must be considered and programs put in place to continuously educate staff who work in these suites.

This talk aims to provide an overview of MR-guided interventional procedures which are currently performed clinically on high-field (>1.5T) cylindrical bore systems with an emphasis on the potential for guidance of thermal ablative therapies. Illustrations of the use of MRI for planning and targeting lesions as well as monitoring and assessing thermal therapy delivery (i.e., cryotherapy and laser ablation) will be presented and challenges associated with these procedures discussed.

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Abstract, 3/11/2013
Computational models to investigate anti-angiogenic cancer therapies targeting the
VEGF pathway
Dr. Stacey Finley

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is a tightly
regulated biological process involved in physiological function such as wound healing and
exercise, as well as in pathological conditions, including preeclampsia, ischemic heart disease,
and cancer. Inducing angiogenesis is a hallmark of cancer, as tumors cannot grow beyond 1
mm in diameter without eliciting the formation of blood capillaries to supply oxygen and other
nutrients. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and its
role in cancer biology has been widely studied. Given the action of VEGF in promoting
angiogenesis, it has been targeted in various cancer treatments.

Systems biology approaches, including experiment-based computational modeling, are useful in
gaining insight into the complexity of tumor angiogenesis. These models provide a framework to
test biological hypotheses and optimize effective therapies that aim to inhibit tumor
vascularization and growth. Here, I describe the development of whole-body, molecular-detailed
compartment models of VEGF kinetics and transport in mice and humans and the application of
these models to predict the effect of various anti-angiogenic therapies that inhibit VEGF. The
mouse model has been fit to available experimental data and complements pre-clinical drug
studies, and the human model is applied to interpret clinical data. Both models reproduce
experimental observations and predict the dynamics of VEGF in the body. Importantly, the
models simulate the effects of intravenous administration of anti-VEGF agents. The model
predictions are relevant to the clinical application of VEGF-targeting therapies and generate
testable hypotheses that can aid in elucidating the mechanism of action of anti-VEGF agents.
This work is useful for the development and optimization of personalized cancer treatment
strategies that target the VEGF pathway.

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Abstract, 3/18/2013
Novel pathways for cardiac matrix assembly
Prof. Alissa Weaver

Extracellular matrix (ECM) secretion and assembly critically contributes to tissue repair and pathophysiologic processes, including cardiac development, and repair of the injured heart. Nonetheless, its deposition by intracellular secretory pathways is not well understood. Recently, we discovered that autocrine secretion of fibronectin (FN) can occur via recycling from a secretory lysosome-like compartment, rather than (or in addition to) the conventional Golgi route. Functionally, this mechanism of matrix recycling promotes efficient and persistent motility of cancer and epicardial cells and is also used for assembly of cell-derived matrices by multiple cell types, including mouse embryonic fibroblasts and cardiac stromal cells. Understanding this novel pathway of matrix assembly may lead to a greater understanding of how extracellular matrix is assembled and remodeled during a variety of tissue conditions.

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Abstract, 4/15/2013
Systems analysis of TGF-beta signaling dynamics
Prof. Xuedong Liu

Transforming growth factor-β (TGF-β) is a prominent signaling pathway crucial for regulating diverse aspects of cellular homeostasis. The physiological responses to TGF-β stimulation are diverse and vary amongst different cell types and environmental conditions. The principal molecular components of TGF-β signaling have been identified yet this knowledge is insufficient to fully account for the known biology. Understanding TGF-β signaling complexity will require adopting a system view of cell function in which the discovery of new molecules and connections is combined with studies of system dynamics. Our research has been focused on understanding the quantitative basis for how TGF-β signals are transduced into both canonical Smad and non-canonical Smad-independent pathway kinetics. Using a combined experimental and modeling approach, we analyzed how cells read TGF-β concentration with high precision to produce different biological responses and demonstrated that the duration and amplitude of cellular response depend on ligand dose. TGF-β ligand depletion can be the principal determinant of the Smad signal duration and account for long term ultrasensitive response to TGF-β signaling. Finally, how TGF-β modulates MAPK signaling networks to regulate coordinated and individual cell migration in epithelial sheets will be discussed.

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Abstract, 4/22/2013
Glucose effects on endothelial cell mechanotransduction
Prof. Alisa Morss Clyne

In a healthy blood vessel, endothelial cells dynamically integrate biomechanical and
biochemical signals from the flowing blood at their apical surface and the basement
membrane at their basolateral surface. In disease, changes in the biochemical
environment may disturb endothelial cell response to mechanical forces, and the
mechanical environment may affect biochemical transport, binding, and signaling. In this
talk, I will present our research demonstrating that altered blood glucose, such as that
experienced by people with diabetes, disturbs endothelial cell response to shear stress and
cyclic strain. I will then describe computational and experimental models of fluid flow
effects on fibroblast growth factor-2 transport, binding, and signaling, and the impact of
this work on drug delivery. Finally, I will show our recent research investigating how
substrate stiffness affects endothelial cell migration, as well as a new device we are
developing to dynamically measure both cell stiffness and mechanotransduction. This
research highlights applications of biomechanical engineering to understand, diagnose,
and treat cardiovascular disease.

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Abstract, 4/29/2013
The importance of multiscale mechanics in tissue engineering and mechanobiology
Prof. Ed Sander

Multiscale mechanical interactions are scale spanning physical interactions between the tissue and the extracellular matrix (ECM). They are involved in a variety of biological phenomena, including tissue growth, remodeling, disease, and damage. These interactions are important to characterize because they control both the mechanical behavior of the tissue and the manner in which mechanical signals are propagated to the cellular level – issues that are particularly important to tissue engineering applications. In this seminar, I will discuss my work with engineered tissues and how developing multiscale computer models can help us better understand these multiscale processes. In doing so, we can devise better protocols for producing functional engineered tissues, as well as understanding the role of these processes in other biological contexts, such as wound healing and disease. An essential component for moving this work forward is the continued development of the physics of cell-ECM interactions from direct observations and image analysis.

Biography: Ed Sander is an assistant professor in the Department of Biomedical Engineering at the University of Iowa. During his postdoctoral training, he was a research associate at the Cincinnati Shriners Hospital for Children and the Department of Surgery at the University of Cincinnati, and an NIH NRSA postdoctoral fellow in the Department of Biomedical Engineering at the University of Minnesota. He obtained his B.S. in Chemical Engineering from the University of Texas at Austin, and his M.Eng. and Ph.D. in Biomedical Engineering from Tulane University.

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Abstract, 5/6/2013
Continuing professional development in an academic medical center: a maintenance of quality issue
Prof. Carla Pugh

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Date Topic Speaker
Monday
9/24/2012
Progress in engineering pluripotency with new models and biomaterials (Abstract) Prof. Krishanu Saha Dept. of Biomedical Engineering
UW-Madison
Monday
10/1/2012
Spectral microscopy for cancer screening (Abstract) Prof. Jeremy Rogers Dept. of Biomedical Engineering
Northwestern University
Evanston, IL
Monday
10/15/2012
Delineating the mechanisms of cell polarity and migration using novel microfluidic devices (Abstract) Cosponsored by LOCI and Prairie Technologies Prof. Christopher Janetopoulos Dept. of Biological Sciences
Vanderbilt University
Nashville, TN
Monday
10/22/2012
Excitable cell disease from in silico to in vivo (Abstract) Prof. Thomas Hund Dept. of Biomedical Engineering and Internal Medicine
The Ohio State University
Columbus, OH
Monday
10/29/2012
Multicompartmental particles and fibers (Abstract) Cosponsored by LOCI and Prairie Technologies Prof. Joerg Lahann Chemical Engineering, Materials Science & Engineering,
Biointerfaces Institute,
University of Michigan,
Ann Arbor, MI
Institute for Functional Interfaces, KIT, Germany
Monday
11/5/2012
Channeling touch and pain transduction: mechanisms that detect our environment (Abstract) Prof. Cheryl Stucky Director, Neuroscience Doctoral Program
Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin
Monday
11/19/2012
Distinguished Lecture Awardee The consequences of cell promiscuity, or whether viruses can cause cancer by fusing cells (Abstract) Prof. Yuri Lazebnik Cold Spring Harbor Laboratory
Cold Spring Harbor, NY
Monday
12/3/2012
How Educational Games can Measure Engineering Thinking and Increase Engineering Enrollment (Abstract) Prof. David Shaffer Dept. of Educational Psychology
School of Education
UW-Madison

Abstract, 9/24/2012
Progress in engineering pluripotency with new models and biomaterials
Prof. Krishanu Saha

Human embryonic stem cells can grow indefinitely in culture and generate all parts of the human body. Therefore, these remarkably plastic cells are termed “pluripotent” and represent attractive resources for tissue engineering and human disease modeling. Making these cells in a standardized and predictable manner however has been problematic, because the methods to derive and propagate these cells are either poorly understood or difficult to scale-up. Through two projects, I will describe engineering approaches to 1) identify and characterize intermediate states in a new technique of deriving pluripotent stem cells and 2) develop new biointerfaces that can efficiently propagate them. The first project dissects stochastic transitions involved in progressing to a pluripotent state through epigenetic reprogramming, and the second project details biomolecules involved in the growth of two types of pluripotent cells.

Biosketch:Krishanu Saha studied Chemical Engineering at Cornell University and at the University of California-Berkeley. In his dissertation with Professors David Schaffer and Kevin Healy, he worked on experimental and computational analyses of neural stem cell development, as well as the design of new materials for adult stem cell culture. In 2007 he became a postdoctoral fellow in the laboratory of Professor Rudolf Jaenisch at the Whitehead Institute for Biomedical Research at MIT in Cambridge, Massachusetts. Since 2006 he has done research on human embryonic stem cells. As a Society in Science – Branco Weiss fellow, Kris is expanding his background to investigate the modeling of diseases at the cellular level with human “reprogrammed” stem cell lines. In Fall 2012, he started as an Assistant Professor of Biomedical Engineering in the Wisconsin Institute for Discovery at the University of Wisconsin-Madison.

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Abstract, 10/1/12
Spectral microscopy for cancer screening
Prof. Jeremy Rogers

In 1953, Danely Slaughter and coauthors published “‘Field Cancerization’ in oral stratified squamous epithelium,” introducing the idea that carcinogenesis may in fact be a local progression of more widespread regional changes in tissue. Since then, studies have provided support for this hypothesis, also known as ‘condemned mucosa syndrome.’ Evidence includes genetic alterations, changes in chromatin texture, and changes in size and shape of the nucleus. While much remains to be understood about the mechanisms of field carcinogenesis, detection of the early changes in epithelial tissue that presage cancer could provide a valuable tool in cancer screening by identifying individuals at elevated risk. Several promising techniques detect changes in nanoarchitecture optically by quantifying changes in light scattering from within cells and tissue. For example, changes in the distribution of macromolecules alter the spectral dependence of scattered light, allowing quantification of disorder associated with cancer risk. Since changes occur throughout a region of tissue, screening can be made less invasive and more cost effective by testing cells from accessible sites.

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Abstract, 10/15/2012
Delineating the mechanisms of cell polarity and migration using novel microfluidic devices
Prof. Christopher Janetopoulos

Chemotaxis plays a vital role during the life cycle of the social amoeba Dictyostelium discoideum. Cells use directed migration to find food during normal growth and also use chemotaxis during aggregation in the developmental phase of the life cycle. My laboratory is using the distinct morphologies of these two different polarized states to elucidate the mechanisms underlying this process. During vegetative growth, unpolarized cells are grown in the presence of bacteria and become competent for folic acid chemotaxis and do not require the developmental program. During aggregation, cAMP-mediated chemotaxis occurs after starvation and the onset of development. These cells can become highly polarized and have a distinct leading and trailing edge. Presumably, the same directional sensing module guides a cell during cAMP and folic acid-mediated chemotaxis. We have used a variety of approaches, including genetic analysis and various chemotaxis assays, to decipher the role of signaling molecules regulating migration in these two cell morphologies. In addition, recent studies using microfluidic devices have given us significant insight into the regulation and the role that polarity plays in directed cell migration. We have developed a unique system that allows us to lure cells into a device, break their polarity down, and then re-establish the polarity in the opposite direction. These cells then reverse course. We have used these devices to characterize the temporal and spatial regulation of signaling and cytoskeletal proteins that are critical for both polarity and migration. We are now using microfluidic technologies we developed for single cell imaging to microfabricate unique devices for intravital imaging. These new devices will permit the real time addition of drugs, dyes and cells to living animals while under microscopic observation.

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Abstract, 10/22/2012
Excitable cell disease from in silico to in vivo Prof. Thomas Hund

Normal ion channel function is essential for many critical physiological functions such as heart contraction, hormone release, and neuronal firing. In excitable cells, normal ion channel function requires proper localization and regulation at specialized membrane domains. However, despite the recent discovery of links between disorganization of local signaling domains and human disease, very little is known regarding the mechanisms underlying the biogenesis, maintenance, or regulation of these critical membrane compartments. Understanding the cellular pathways responsible for targeting and regulation of ion channels and transporters to specific subcellular domains, therefore, represents an emerging area with great potential for generating new insight into human excitable cell diseases (e.g. cardiac arrhythmia, diabetes, epilepsy). This seminar will present our work integrating molecular and cell biology, computational biology, and physiology to identify novel mechanisms underlying excitable cell disease.

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Abstract, 10/29/2012
Multicompartmental particles and fibers
Prof. Joerg Lahann

Electrohyrodynamic co-jetting involves the co-processing of multiple fluid flows with distinct chemical composition in electrical fields. Depending on the process conditions, it can result in either particles or fibers, which are comprised of two or more distinct compartments. The colocation of multiple compartments within the same nanoparticle (or nano/microfiber) can lead to unique, previously unseen sets of properties. Examples of multicompartmental particles and fibers for drug delivery, combined delivery and imaging, microactuators, and regenerative medicine will be discussed.

  1. S. Saha, D. Copic, S. Bhaskar, N. Clay, A. Donini, A.J. Hart, J. Lahann, Chemically Controlled Bending of Compositionally Anisotropic Microcylinders, Angewandte Chemie International Edition 2012, 51, 660- 665.
  2. J. Lahann, Recent Progress in Nano-biotechnology: Compartmentalized Micro- and Nanoparticles, Small 2011, 7, 9, 1149-1156.
  3. N. Doshi, A.S. Zahr, S. Bhaskar, J. Lahann, S. Mitragotri, Red Blood Cell- Mimetic Particles: Bridging the Gap between Synthetic and Biological Materials, Proceedings of the National Academy of Sciences 2009, 106, 21495–21499.
  4. S. Bhaskar, J. Lahann, Microstructured Materials based on Multicompartmental Fibers, Journal of the American Chemical Society 2009, 131, 6650.
  5. S. Bhaskar, J. Hitt, S.-W.L. Chang, J. Lahann, Multicompartmental Microcylinders, Angewandte Chemie International Edition 2009, 48, 4589- 4593.
  6. M. Yoshida, K.-H. Roh, S. Mandal, S. Bhaskar, D. Lim, H. Nandivada, X. Deng, J. Lahann, Structurally controlled bio-hybrid materials based on unidirectional association of anisotropic microparticles with human endothelial cells, Advanced Materials 2009, 21, 4920–4925.
  7. K.-H. Roh, D. C. Martin, J. Lahann, Triphasic Nanocolloids. Journal of the American Chemical Society 2006, 128, 21, 6796-6797.
  8. K.-H. Roh, D.C. Martin, J. Lahann, Biphasic Janus Particles with Nanoscale Anisotropy. Nature Materials 2005, 4(10), 759-763.

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Abstract, 11/05/2012
Channeling touch and pain transduction: mechanisms that detect our environment
Prof. Cheryl Stucky

Mechanotransduction is a fundamental process by which we interact with our environment on a daily basis. Mechanotransduction is an integral part of our lives from the first moments of life through the bond that forms between a baby and mother, to feedback in our fingers from writing grants and manuscripts on computers, to the pain systems that unconsciously project our joints, muscles and skin from overly forceful movements and damaging environmental impacts on a moment-to-moment basis. Mechanotransduction can also have a seriously negative impact. Many patients that have chronic pain disorders such as neuropathic pain from trauma, post-herpetic pain after shingles, or chemotherapy-induced neuropathies have such extreme hypersensitivity to light touch that this profoundly reduces their quality of life and activities enjoyed. Despite its fundamental role in our lives, mechanotransduction remains one of the key unsolved questions in the somatosensory field. The identity of mechanosensitive channels and proteins that underlie these processes are still largely unknown and we have only a few putative candidates to date. One of the candidates is the Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel which is found on sensory neurons and other cell types in skin. My laboratory has been using a battery of approaches to investigate mechanotransduction candidates such as TRPA1 for their roles in normal touch detection and mechanical hypersensitivity and pain after injury. These approaches include quantitative mechanical stimulation of receptive fields of identified single neurons in teased fiber electrophysiological recordings from skin-nerve preparations, focal mechanical probing of the cellular membrane during whole cell patch clamp recordings of identified sensory neuron subtypes, functional calcium imaging of identified neurons and behavioral response assays in whole animals. We combine these approaches with genetically-modified mice, pharmacological compounds and the use of preclinical rodent pain models such as peripheral inflammation, nerve injury and a model of sickle cell disease pain.

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Abstract, 11/19/2012
The consequences of cell promiscuity, or whether viruses can cause cancer by fusing cells
Prof. Yuri Lazebnik

A remarkable aspect of the discovery that human papilloma virus (HPV) causes cancer is that for the preceding six decades this virus had been viewed as benign. This fact suggests that today we may be disregarding other major causes of this disease. An accidental observation led us to a long-standing candidate – cell fusion, a fundamental, yet poorly understood and often overlooked process. We have proposed a model that viruses can cause cancer and its progression by fusing cells to each other. This model is based on several observations: i) common infectious human viruses, including herpes virus, indiscriminately fuse cells in the body; ii) human endogenous retroviruses, some of which can fuse cells, are often expressed in common cancers; iii) multinucleated tumor cells, whose origin is unknown, are common in cancers and are typical to some; iv) cell fusion causes conditions characteristic for cancer cells, such as chromosomal instability, epigenetic plasticity, heterogeneity, and diversity of abnormal cell types; v) cell fusion can nearly instantaneously create abnormal new cell types or produce dedifferentiated cells; vi) circulating bone marrow cells fuse to resident cells of several organs, especially following injury or inflammation; vii) fusion of non-tumorigenic human cells can produce cancerous hybrids; viii) fusion between cancerous and host cells has been demonstrated in experimental models of cancer. Our research has focused on testing this model.

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Abstract, 12/03/2012
How Educational Games can Measure Engineering Thinking and Increase Engineering Enrollment
Prof. David Shaffer

In this talk, Professor David Shaffer looks at engineering thinking: what makes it unique, how we can measure it, and how we can motive students to develop it using computer games. The result is a perspective on engineering teaching and assessment for the realities of professional practice in the 21st Century. Dr. Shaffer will discuss the results of NSF-funded research currently being used in the UW Engineering curriculum and at other schools in the US.

Biosketch:David Shaffer is a Professor at the University of Wisconsin-Madison in the Department of Educational Psychology and a Game Scientist at the Wisconsin Center for Education Research. Before coming to the University of Wisconsin, Dr. Shaffer taught grades 4-12 in the United States and abroad, including two years working with the Asian Development Bank and US Peace Corps in Nepal. His M.S. and Ph.D. are from the Media Laboratory at the Massachusetts Institute of Technology, and he taught in the Technology and Education Program at the Harvard Graduate School of Education. Dr. Shaffer was a 2008-2009 European Union Marie Curie Fellow. He studies how new technologies change the way people think and learn, and his most recent book is ‘How Computer Games Help Children Learn’.

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