University of Wisconsin Madison College of Engineering

Biomedical Engineering Seminar Series

The Dept. 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 on Mondays at noon in the Tong Auditorium (Room 1003 Engineering Centers Building, 1550 Engineering Drive) unless otherwise indicated.


Biomedical Engineering Spring 2015 Seminar Program

 

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, 5/4/2014
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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