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 2014 Seminar Program

 

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 mechanical regulator of lung branching morphogenesis
(Abstract)

Jason Gleghorn, Ph.D.
School of Engineering and Applied Science
Princeton University

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 5x103 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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