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UCR Bioengineering 2008 Seminar Series

2008-2009 COLLOQUIUM

Date

Speaker

Title

2008-10-15 Daniel Kamei
UCLA
Engineering Molecular Therapeutics
2008-10-29 Gerard Coté
Texas A & M
Distinguished Speaker Series
Optically-Based Biomedical Sensing Approaches
2008-11-05 Nagarajan Vaidehi
Beckman Institute, City of Hope
Ligand Induced Conformation Changes in G-protein Coupled Receptors: Insight into Activation and Ligand Efficacy
2008-11-19 John Nolan
La Jolla Bioengineering Institute
Single Particle Raman Spectroscopy in Flow: Making the Most of the Spectrum for Multiparameter Cell and Molecular Analyses
2008-12-03 Michael Khoo
USC
Distinguished Speaker Series
Autonomic Cardiovascular Control and Sleep-Disordered Breathing in Obesity: from Computational Models to Translational Research Studies
2009-01-14 Steven George
UC Irvine
Distinguished Speaker Series
Tissue Remodeling and Nitrogen Oxide Biology in Asthma: A Multiscale Integrative Approach
2009-01-21 Henry Lowman
Genentech
Engineering Antibodies for Altered Effector Function
2009-01-28 Marc Facciotti
UC Davis
Deciphering Gene Regulatory Networks with Systems Approaches
2009-02-11 Kara McCloskey
UC Merced
Vascular Stem Cell Differentiation for Regenerative Medicine
2009-02-18 Dimiter N. Petsev
University of New Mexico
Transport Control in Fluidic Micro and Nanochannels
2009-02-25 Laura Marcu
UC Davis
Fluorescence Lifetime Tissue Diagnostic Techniques: A Clinical Translational Research Perspective
2009-03-11 Stephen White
UC Irvine
Distinguished Speaker Series
How Membranes Shape Protein Structure--and Vice Versa
2009-04-01 Larry McIntire
Georgia Tech
Distinguished Speaker Series
Role of Mechanical Forces in Vascular Biology
2009-04-15 Anand R. Asthagiri
Caltech
Predicting and Tuning Multicellular Morphodynamics
2009-04-29 James Brody
UC Irvine
Reverse Engineering Transcriptional Control Systems using Surface Plasmon Resonance Measurements of DNA/protein Binding
2009-05-13 Michael Shuler
Cornell
Distinguished Speaker Series
"Body-on-a-Chip": A Tool for Predictive Pharmacology/Toxicology
2009-05-20 Daniel Gryko
Polish Academy of Science
Corroles – From Synthesis to Photophysics
2009-05-27 Karen Christman
UC San Diego
Injectable Materials for Treating Myocardial Infarction and Heart Failure

All colloquium presentations are held on Wednesdays from 11:00-noon unless otherwise noted.

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October 15 , 2008, A265 Bourns Hall Kamei

Daniel Kamei, Assistant Professor of Biomedical Engineering, UCLA

Title: Engineering Molecular Therapeutics

The goal of my laboratory is to develop an integrative methodology for identifying innovative solutions to engineering molecular therapeutics. This methodology incorporates a systems approach to modeling biological systems, quantitative cellular experiments, and the development of new diagnostic tools. The modeling is performed to identify novel design criteria for engineering more efficacious therapeutics, while the quantitative cellular experiments are conducted to test our model predictions, as well as to obtain information to establish new hypotheses and models to be tested. In addition to directly changing the molecular architecture of therapeutics, we are striving to improve the sensitivity of diagnostic tools to aid in the early detection of diseases, which may then promote the treatment of the diseases by a greater variety of therapeutics. Developing molecular therapeutics with such an integrative methodology can potentially save time, resources, and animal testing, while simultaneously having a higher probability of success in clinical trials. In this presentation, I will discuss two of our projects in the area of drug delivery. One project involves a unique approach to engineering the intracellular trafficking pathway of a protein used in targeting chemotherapeutics to cancer cells, whereas the other project investigates a new class of nanoscale encapsulants, namely polypeptide vesicles.

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October 29, 2008, Distinguished Speakers Series, A265 Bourns Hall Cote

Gerard Coté, Charles H. & Bettye Barclay Professor and Head Department of Biomedical Engineering, Texas A&M University

Title: Optically-Based Biomedical Sensing Approaches

The objective of this presentation is to provide an overview of some recent advances in noninvasive and implantable optically based diagnostic and sensing techniques to the nano-scale. Specifically discussed are four optical sensing methods being investigated in our Optical Biosensing Laboratory at Texas A&M University and around the World including; infrared absorption spectroscopy, polarimetry, surface enhanced Raman spectroscopy and fluorescence spectroscopy. Emphasis will be placed on using these technologies for a variety of applications such as perfusion monitoring for liver transplant and beta-amyloid detection for Alzheimer’s disease but the bulk of the talk will include development of some of these approaches for glucose monitoring for diabetes.

Dr. Coté is Head of the Department of Biomedical Engineering and holds the Charles H. and Bettye Barclay Professorship in Engineering at Texas A&M University. After receiving his Ph.D. and master’s in bioengineering from the University of Connecticut, Storrs in 1990 and 1987 respectively as well as a bachelor’s degree in electrical engineering from the Rochester Institute of Technology in 1986, he joined the Texas A&M Engineering faculty in 1991 as an assistant professor and was named professor in 2002. Dr. Coté directs the Optical Biosensing Laboratory, where research focuses on the development of macro-scale to nano-scale systems using lasers, fiberoptics and electronics for new, noninvasive ways to test blood sugar levels in diabetes; to detect other body chemicals such as beta amyloid for Alzheimer’s disease; and to optically study perfusion and lymphatic flow. Dr. Coté has had funded research from NIH, NSF, NASA, DOD, private foundations, and private companies resulting in over 200 journal publications, proceedings, and presentations. He has written five book chapters and is a co-holder of four U.S. patents and 4 more disclosures. He is a co-founder of three small medical device companies and is a Fellow of the American Institute for Medical and Biological Engineering.

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November 5 , 2008, A265 Bourns Hall NV

Nagarajan Vaidehi, Professor of Immunology, Beckman Research Institute of the City of Hope

Title: Ligand Induced Conformation Changes in G-protein Coupled Receptors: Insight into Activation and Ligand Efficacy

One of the major hurdles in obtaining structural information for GPCRs is the conformational flexibility and ligands of varied efficacies increase or decrease this conformational flexibility. Agonists, partial agonists, inverse agonists, antagonists and allosteric modulators have different effects on the receptor conformation depending on its binding affinity and efficacy. 3D structural information of these ensemble of conformations stabilized by various ligands would be very critical to understand the molecular basis of ligand efficacy. To this end, we have developed a computational method, Ligand Induced Transmembrane Conformational changes (LITiCon), based on simultaneous optimization of the ligand induced movement of the seven transmembrane helices, followed by molecular dynamics simulations in explicit lipid and water for predicting the conformational changes that occur on ligand binding. I will present results on our studies on the activation mechanism of rhodopsin and beta-adrenergic receptors using Liticon.

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November 19 , 2008, A265 Bourns Hall  

John Nolan, Professor, La Jolla Bioengineering Institute

Title: Single Particle Raman Spectroscopy in Flow: Making the Most of the Spectrum for Multiparameter Cell and Molecular Analyses

Multiparameter measurements are an important tool for understanding of complex cell systems. In flow cytometry, and other fluorescence measurement platforms, the number of individual reporters that can be resolved is limited by the spectral line widths of fluorescence probes and the spectral range accessible with available light sources and detectors. Raman spectra have much narrower spectral features, allowing much more information to be encoded within a given spectral space. Surface-enhanced Raman scattering (SERS) from metal nanoparticles offers an alternative to fluorescence probes to expand the level of multiparameter analysis. We have developed a Raman Flow Cytometer, and are using this to measure SERS spectra from metal nanoparticle probes. We are engineering metal nanoparticle systems to have a plasmon resonance tuned to specific illumination wavelengths and bearing a resonant molecule that provides a distinctive spectral signature. High throughput analysis of individual nanoparticles allows us to rapidly assess the brightness, uniformity, and yield of SERS nanoparticle preparations. Raman spectral analysis of plasmonic nanoparticle probes provides a powerful new complement to fluorescence for to multiparameter cell and molecular analysis using flow cytometry.

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December 3, 2008, Distinguished Speakers Series, A265 Bourns Hall khoo

Michael Khoo, Professor and Dwight C. & Hildagarde E. Baum Chair, Department of Biomedical Engineering, University of Southern California

Title: Autonomic Cardiovascular Control and Sleep-Disordered Breathing in Obesity: from Computational Models to Translational Research Studies

There is ample evidence to support the notion that chronic exposure to repetitive episodes of interrupted breathing during sleep, along with frequent brief arousals from sleep, are independent predictors of systemic hypertension, heart failure, myocardial infarction and stroke. Recent studies have suggested that abnormal autonomic control may be the common factor linking sleep-disordered breathing (SDB) to these cardiovascular diseases. The spontaneous variabilities observed in measurements of respiration, heart rate, blood pressure and sleep-wake state reflect the dynamics of complex interactions that take place among the underlying physiological mechanisms. Due to the abundance of feedback and feedforward connections, it is generally difficult to delineate these mechanisms by applying traditional "open-loop" physiological techniques, particularly in studies involving human data. In this talk, I will present an overview of the closed-loop minimal modeling and structured modeling approaches we have employed in the past several years to unravel useful information about the main mechanisms that mediated these complex state-cardiorespiratory interactions. Obesity is highly prevalent in subjects with SDB. A significant fraction of these subjects also develop Type 2 diabetes. Thus, a new direction in our research is focused on better understanding the links between SDB and insulin resistance in obese individuals.

Michael C. K. Khoo is Professor and the Dwight C. and Hildagarde E. Baum Chair of Biomedical Engineering at the University of Southern California. He obtained his undergraduate training in mechanical engineering from Imperial College of Science and Technology, University of London, and his Master’s and Ph.D. degrees in bioengineering from Harvard University. He is also Co-Director of Education and Outreach in the NSF-funded Biomimetic Microelectronic Systems Engineering Research Center at USC. His research interests include cardiorespiratory regulation and variability in sleep apnea, physiological modeling, and biomedical signal processing. Dr. Khoo is a Fellow of the Biomedical Engineering Society and the American Institute of Medical and Biological Engineering. He is also a member of the IEEE, American Physiological Society, Sleep Research Society and the American Heart Association. Starting in January 2009, he will serve as a member of the Engineering in Medicine and Biology Society Administrative Committee. He is the author of the biomedical engineering textbook: Physiological Control Systems: Analysis, Simulation and Estimation (Piscataway, NJ: Wiley-IEEE Press, 2000).

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January 14, 2009, Distinguished Speakers Series, A265 Bourns Hall george

Steven George, The William J. Link Professor and Chair, Department of Biomedical Engineering, University of California, Irvine

Title: Tissue Remodeling and Nitrogen Oxide Biology in Asthma: A Multiscale Integrative Approach

Asthma is a disease that conservatively afflicts 7% of the population. It is characterized by inflammation and chronic repetitive bouts of bronchoconstriction (narrowing of airway lumens) that cause difficulty in breathing, but also lead to structural changes in the airway wall termed “airway remodeling” which includes subepithelial fibrosis. The hallmark of therapy is inhaled corticosteroids to reduce inflammation which may also modulate the remodeling process, but is not without untoward side effects due to the chronic nature of the disease. Exhaled nitric oxide is elevated in untreated asthma, but is reduced following steroid therapy. Thus, exhaled nitric oxide may be a useful non-invasive marker of inflammatory status and could prove useful in titrating corticosteroid dose. Our lab has used a variety of engineering (mathematical models, mass transfer, signal processing, parameter optimization, optical imaging) and biological (primary cell culture, protein and gene expression) approaches to improve our understanding of asthma. This seminar will explore tissue engineered and mathematical models of the airway mucosa and lungs and novel optical imaging methods (e.g., second harmonic generation and optical coherence tomography) as tools to understand nitric oxide metabolism and subepithelial fibrosis in airway remodeling.

Dr. George received his bachelors degree in chemical engineering in 1987 from Northwestern University, M.D. from the University of Missouri School of Medicine in 1991, and Ph.D. from the University of Washington in chemical engineering in 1995. He then joined the faculty at the University of California, Irvine. His research interests include tissue engineering and pulmonary gas exchange with particular interest in mechanisms underlying airway fibrosis, angiogenesis, and exhaled nitric oxide in asthma. His research program is currently supported by the National Institutes of Health, and has previously been recognized by the NIH FIRST award in 1998 and the CAREER and Presidential Early Career Award for Scientists and Engineers (PECASE) from the National Science Foundation in 1999. He became the Director of the Center for Biomedical Engineering in October, 2000, and served as the Principal Investigator of the Development Award from the Whitaker Foundation from 2000-2006. He was elected a fellow in the American Institute of Medical and Biological Engineering (AIMBE) in 2006. He is the founding William J. Link Professor and Chair of the Department of Biomedical Engineering and has served in this role since 2002.

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January 21, 2009, A265 Bourns Hall lowman

Henry Lowman, Director, Antibody Engineering Group, Genentech, Inc., San Francisco, CA

Title: Engineering Antibodies for Altered Effector Function

Antibodies are natural inhibitors of protein-protein interactions, mediators of immune response, and in some cases agonists of cell signaling events. The CDR-loop containing variable region of a typical IgG immunoglobulin (VH and VL domains), whether derived from in vivo immune response or from combinatorial diversity libraries, can be selected for exquisite specificity and high affinity for a particular therapeutic target. The conserved Fc region of the immunoglobulin is responsible for interactions with effector molecules such as Fc receptors and the complement system, as well as FcRn, an important mediator of in vivo antibody half-life. These interactions can also be mediated through site-specific mutation. To engineer antibodies as successful therapeutics, we make use of structure-based design in combination with screening assays that reveal the binding specificity, affinity, and kinetics of antibody variants for their antigen and for effector molecules, as well as their in vitro and in vivo biological activity. This talk will focus on our approaches to engineering the antigen-binding specificity as well as the effector functions of antibodies for the development of therapeutic candidates.

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January 28, 2009, A265 Bourns Hall Marc

Marc Facciotti, Assistant Professor, Department of Biomedical Engineering and UC Davis Genome Center, UC Davis

Title: Deciphering Gene Regulatory Networks with Systems Approaches

The list of organisms whose genomes have been completely sequenced is growing quickly and advances in sequencing technologies are soon poised to dramatically increase the rate of complete genome sequencing. We believe that encoded within these genomes lie the answers to numerous unresolved questions in biology including, but not limited to, explanations for the molecular etiology of complex disease, novel catalysts for industrial application and key insights into cellular organization. One of the main barriers to approaching these questions is the development of complimentary experimental and computational tools. Modern systems biology approaches, driven by cellularly global measurement technologies, offer a fantastic opportunity to overcome such challenges. From a cellular engineering standpoint, it is highly desirable to use systems approaches to view hidden relationships between numerous cellular processes that are not otherwise easily observable. I will discuss advances in the application of systems biology methods in the novel model organism Halobacterium salinarum NRC-1 for learning structures of global gene regulatory networks for free living organisms from omic data alone and discuss how this and other coming advances should affect our ability to rationally engineer novel phenotypes.

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February 11, 2009, A265 Bourns Hall Kara

Kara McCloskey, Assistant Professor of Engineering, UC Merced

Title: Vascular Stem Cell Differentiation for Regenerative Medicine

Vascular progenitor cells derived from stem cells could potentially lead to a variety of clinically relevant applications including cell-based therapies and tissue engineering. Two obstacles associated with using embryonic stem cells (ESC) for regenerative medicine applications include a) isolating homogeneous populations of differentiated cells that will not form teratomas and b) obtaining terminally differentiated cell populations that are fully functional and retain significant expansion potential. Our laboratory has investigated both vascular endothelial and vascular smooth muscle cell differentiation, developed methods for differentiation and isolation of homogeneous differentiated cell populations, and characterized these cells for both surface and functional markers. Comparisons of in vitro-derived EC with “normal” in vivo mouse aortic endothelial cells (MAEC) indicate that both ESC-derived ECs and MAEC are approximately the same size and have comparable proliferation rates, marker expression, synthesize similar levels of nitric oxide, and regulate permeability. It is also interesting to note that MAEC do not exhibit the same level of vasculogenic properties as ESC-derived EC, a potential indicator that ESC-derived EC are not completely “mature” cells and, therefore, a potentially ideal cell source for vasculogenic therapies. We have also explored their potential for building neovessels in vitro and have been expanding these studies into cardiac differentiation and development towards a functional cardiac patch.

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February 18, 2009, A265 Bourns Hall petsev

Dimitar Petsev, Assistant Professor, Center for Biomedical Engineering and Department for Chemical and Nuclear Engineering, University of New Mexico

Title: Transport Control in Fluidic Micro and Nanochannels

 

Micro and nanofluidics have a great potential for implementation in a variety of new technologies and applications. Examples include chemical and biomolecular sensing, separation, biomolecule manipulation, sample preconcentration and focusing, conducting small scale liquid reactions, monodisperse droplet and particles fabrication. As the channels dimensions become smaller, the Reynolds numbers characterizing the flow become lower and the viscous effects become dominant. A typical example is mixing, which for micro and nanofluidic devices requires completely new approaches. Controlling the fluids, current and analytes in fluidic systems also requires the development of pumps and valves to direct and manipulate the liquid and dissolved species. Nanochannels present an additional complexity due to strong electrostatic potential effects in the electric double layers at the channel walls. These lead to difficulties but also give rise to new opportunities for the processing of fluids and analytes. This presentation summarizes some of our recent results on fluid control and manipulation in micro and nanochannels. We suggest a new approach for designing micropumps, mixers and separators using semiconductor diodes powered by an alternate current electric field. A theoretical analysis of the electric field distribution in fluidic nanochannels offers strategies for transport control at the nanoscale. Finally we demonstrate the utility of microfluidics to fabricate monodisperse particles with well defined sized and internal mesoporous structure.

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February 25, 2009, A265 Bourns Hall laura

Laura Marcu, UC Davis

Title: Fluorescence Lifetime Tissue Diagnostic Techniques: A Clinical Translational Research Perspective

In biomedical applications, fluorescence measurements have the potential to provide information about biochemical, functional and structural changes in fluorescent bio-molecular complexes in tissues and cells, such as structural proteins, enzyme metabolic co-factors, lipid components, and porphyrins. Typically, these changes result from either pathological transformation or therapeutic intervention. We have research the development of techniques that utilizes label-free fluorescence lifetime contrast to detect such changes in-vivo. This presentation will overview the time-resolved fluorescence spectroscopy (TRFS) and fluorescence lifetime imaging microscopy (FLIM) techniques researched in our lab; and studies that demonstrate the translational potential of these techniques and show that intrinsic fluorescence signals can provide useful contrast for the diagnosis of high-risk atherosclerotic plaques, primary brain tumors and head and neck tumors. Finally, I will present more recent studies concerning the development of a multi-modal platform combining TRFS with ultrasonic approaches – an effort that is to enable simultaneous detection of tissue biochemistry and morphology, thus the advancement of more effective pathways for diagnosis of pathologies in tissues.

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March 11, 2009, Distinguished Speakers Series, A265 Bourns Hall white

Stephen White, Professor of Physiology & Biophysics, University of California, Irvine

Title: How Membranes Shape Protein Structure--and Vice Versa

The slowly accumulating crystallographic structures of membrane proteins (MPs) reveal that MPs are far more complex than bacteriorhodopsin, which is often taken as the archetypal MP. Because of the slow rate of progress in structure determination and the importance of MPs as drug targets, the prediction of structure from sequence remains a significant and pressing goal. The prediction of 3D structure from sequence requires a detailed understanding of (1) the thermodynamic stability of proteins in the unexpectedly complex environment of the lipid bilayer and (2) the rules the SecY/Sec61 translocon follows during the constitutive assembly of MPs. Several aspects of MP folding will be discussed, including X-ray and neutron diffraction studies of fluid lipid bilayers, experimentally determined whole-residue hydrophobicity scales, folding in bilayer interfaces, transmembrane (TM) helix energetics, and translocon-assisted MP folding.

Stephen White is Professor of Physiology and Biophysics, University of California at Irvine. He received his B.S. in physics from the Univ. of Colorado (1963) and his Ph.D. in Biophysics from the University of Washington in Seattle (1969). He has broad research interests in the areas membranes and membrane protein biophysics, including protein folding in membranes, membrane protein structure prediction, and membrane structure and stability using methods ranging from x-ray and neutron diffraction to molecular biology. He served to the rank of Captain, US Army (1969-1971) and then completed postdoctoral work in lipid biochemistry at the University of Virginia. He joined the faculty of the Dept. of Physiology and Biophysics at UC Irvine in 1972 as an assistant professor, becoming full professor in 1978. He chaired the Department from 1977-1989 and is an alumnus of the Univ. of California Management Institute. He is a member of the Society of General Physiologists, American Crystallographic Association, American Physical Society, American Society for Biochemistry and Molecular Biology, the American Physiological Society, the Protein Society, and the Biophysical Society. He has served in several leadership positions in the Biophysical Society, including Council member, Executive Board member, Program Chairman, Secretary, and President (1996). He has served on many advisory committees for the National Science Foundation, the Department of Energy, and the National Institutes of Health, and is currently a member of the Biochemistry and Biophysics of Membranes Study Section. His honors include an NIH Research Career Development Award, two Kaiser-Permanente Awards for Excellence in Teaching, the Biophysical Society Distinguished Service Award, Biophysical Society Fellow, the 2009 Avanti Award in Lipids (Biophysical Society), and a Ph.D. honoris causa from Stockholm University (2008).

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April 1, 2009, Distinguished Speakers Series, A265 Bourns Hall mcintire

Larry McIntire, The Wallace H. Coulter Chair and Professor, Department of Biomedical Engineering, Georgia Institute of Technology

Title:Role of Mechanical Forces in Vascular Biology

Understanding the molecular basis of the modulation of vascular phenotype by mechanical forces (stresses induced by blood flow and vessel wall strain) is an area of great significance in vascular biology. It is hypothesized that certain flow environments (arterial flow, non-reversing) lead to anti-atherogenic endothelium, while low mean wall shear stress reversing flows promote a pro-atherogenic endothelium. We examined in a flow chamber human endothelial cells exposed to high (15 dynes/cm2) and low (1 dyne/cm2) steady shear stress and a reversing waveform characteristic of the carotid sinus (time average 1 dyne/cm2) using whole human genome microarray studies. We demonstrated unique sets of genes controlled by both low average shear stress and by reversing flow, with more genes controlled by low average stress. Functional studies confirmed that reversing flow increases cell proliferation and monocyte adhesion. Detailed studies of two cytochrome P450 genes that are maximally up-regulated by steady arterial levels of shear stress (CYP1A1 and CYP 1B1) demonstrated strong attenuation by reversing flows. Furthermore, CYP1A1 protein and AhR nuclear localization correlate with flow patterns in the mouse aortic arch in vivo. Finally, as a result of changes observed in zinc-binding and zinc transporter proteins, changes in free zinc were measured under different shear stresses. High steady shear stress exposure dramatically increases the levels of free zinc in endothelial cells.

Dr. Larry V. McIntire joined the Georgia Institute of Technology and the Emory University School of Medicine in 2003 as the Wallace H. Coulter Professor and Chair of the Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. Dr. McIntire received his BChE and MS degrees from Cornell University in 1966 and his PhD from Princeton University in 1970 ‐‐ all in chemical engineering. He joined Rice University in January 1970 as an Assistant Professor. Dr. McIntire served as Chair of the Department of Chemical Engineering from 1982‐1989, the E.D. Butcher Professor at Rice from 1982‐2003, the founding Chair of the Bioengineering Department there from 1997‐2003 and the Chair of the Institute of Biosciences and Bioengineering from 1991‐2003. He is the author of more than 400 publications and papers in the areas of bioengineering applications in vascular biology, thrombosis, atherosclerosis, and inflammation. Dr. McIntire is also a Founding Fellow and past President of the American Institute of Medical and Biological Engineering. He is past President and Fellow of the Biomedical Engineering Society and past President of the North American Society of Biorheology and a Fellow of the American Heart Association. Dr. McIntire was the 1992 recipient of the American Institute of Chemical Engineering Food, Pharmaceutical, and Bioengineering Division Award, Chair of that Division in 1998, elected a Fellow of that Institute in 1994, the 1992 ALZA Distinguished Lecturer for the Biomedical Engineering Society, Sigma Xi National lecturer for 1993‐95 and in 1998, he was elected a Fellow of the American Association for the Advancement of Science. In 2001, Dr. McIntire was elected to the National Academy of Engineering and was appointed Editor‐in‐Chief of the Annals of Biomedical Engineering (the journal of the Biomedical Engineering Society), effective January 2002. Additionally, Dr. McIntire is also the 2003 recipient of the BMES Distinguished Service Award and Presidential Award.

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April 15, 2009, A265 Bourns Hall Anand

Anand R. Asthagiri, Assistant Professor, Division of Chemistry and Chemical Engineering, California Institute of Technology

Title: Predicting and Tuning Multicellular Morphodynamics

Multiple environmental cues control the behavior of individual cells and their organization into multicellular structures. Uncovering how cells integrate these cues to achieve an organized, functional structure is a fundamental challenge in biology with important biomedical implications in areas, such as tissue engineering and regenerative medicine. My lab investigates how signals in the cellular microenvironment program multicellular patterns and structures using quantitative experimental approaches coupled to mathematical modeling. In this talk, I will present how we are leveraging two seemingly distant biological systems – the nematode C. elegans and human epithelial cells – to delineate strategies for predictive tuning of multicellular dynamics. Through mathematical modeling, we have gleaned insights about molecular networks that govern multicellular patterning in the model organism, C. elegans. Our analysis reveals that quantitative perturbations to the molecular network (even without wholesale changes in network architecture) can give rise to significant diversity of multicellular phenotypes. By comparing our model predictions to large experimental data sets, we can effectively re-trace the quantitative changes that have accrued within the biomolecular network during the natural evolution of C. elegans and several related species. In addition to fundamental insights regarding the evolvability of multicellular structures, our lab investigates multicellular patterning in human epithelial cell systems that are directly related to human health and disease. We apply quantitative experimental approaches, including automated single-cell imaging, to better understand the (dis)assembly of multicellular epithelial structures. Our results reveal how the interplay between local cell-cell contact and global soluble cues regulates epithelial population growth and aggregation dynamics. I will discuss how our findings advance our current understanding of oncogenesis and provide design strategies for tissue engineering applications.

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April 29, 2009, A265 Bourns Hall Brody

James Brody, Associate Professor, Department of Biomedical Engineering, UC Irvine

Title: Reverse Engineering Transcriptional Control Systems using Surface Plasmon Resonance Measurements of DNA/protein Binding

Transcription is controlled by multi-protein complexes binding to short non-coding regions of genomic DNA. These complexes interact to enhance or repress transcription. Using surface plasmon resonance on a chip, we can measure DNA protein binding. Combining this with measurements of mRNA expression, we can infer boolean logic expressions that represent transcriptional control system.

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May 13, 2009, Distinguished Speakers Series, A265 Bourns Hall shuler

Michael Shuler, James & Marsha McCormick Chair, Department of Biomedical Engineering, Samuel B. Eckert Professor of Chemical Engineering, School of Chemical & Biomolecular Engineering, Cornell University

Title: "Body-on-a-Chip": A Tool for Predictive Pharmacology/Toxicology

We seek to understand the response of the human body to various pharmaceutical and environmental chemicals as well as to oral ingestion of nanoparticles. Our platform technology is an in vitro system that combines microfabrication and cell cultures and is guided by a computer model of the body. We called this in vitro system a micro cell culture analog (microCCA). A microCCA device contains mammalian cells cultured in interconnected micro-chambers to represent key body organs linked through the circulatory system and is a physical representation of a physiologically based pharmacokinetic (PBPK}model. MicroCCAs can reveal toxic effects that result from interactions between organs as well as provide realistic, inexpensive, accurate, rapid throughput toxicological studies that do not require animals. The advantages of operating on a microscale include the ability to mimic physiological relationships more accurately as the natural length scale is order of 10 to 100 microns. The basic concept has been described in the context of microdevices to study toxicity (see 1-3). We have done “proof-of-concept” experiments as a basis to evaluate combination therapy for cancer. Multidrug resistant (MDR) cancer often occurs after initial success with a chemotherapeutic drug. MDR cancer cannot be treated with the original drug as well as many other drugs. A common form of MDR is overexpression of P-glycoprotein which can be expressed in MDR cells at 50 to 100 fold over normal levels. P-glycoprotein is a pump protein that intercepts drugs and pumps them back out of the cell. Here we test a possible combination treatment using a chemotherapeutic drug, doxorubicin, and two MDR suppressors (cyclosporine and nicardipine). The microCCA (with “liver”, “bone marrow”, “uterine cancer”, “slowly perfused” and “rapidly perfused” compartments) shows a synergistic response to certain drug combinations. We have also used a microCCA to test potential combination therapies (Tegafur and uracil) for colon cancer. Tegafur is a prodrug for 5-FU and uracil an inhibitor of DPD, an enzyme which deactivates 5-FU. Simple microwell plates cannot probe this system, but the microCCA predicts the types of responses observed experimentally. We have coupled these body modules with a micro model of the GI tract to examine the response to oral exposure of drugs, chemicals, or nanoparticles. These coupled GI tract/body modules have been used to mimic human response to acetaminophen plus ethanol and have shown that nanoparticles can interfere with normal physiological responses such as iron uptake and nutrition. Overall, we believe that in vitro, microfabricated devices with cell cultures provides a viable alternative to animal models to predict toxicity. For this proposal we seek to develop and apply a “Body-on-a-Chip” device to a significant issue in the development of pharmaceutical treatment of human disease. A Qatar partner with an interest in combination therapy to treat cancer would be ideal, especially for drugs delivered orally. However, we are open to collaborations involving other diseases and any made of drug delivery.

Michael L. Shuler is the James and Marsha McCormick Chair of the Department of Biomedical Engineering as well as the Samuel B. Eckert Professor of Chemical Engineering in the School of Chemical and Biomolecular Engineering at Cornell University, Ithaca, New York. He was also a NYSTAR Distinguished Professor (2001-2006). Shuler received both of his degrees in chemical engineering (BS, University of Notre Dame, 1969 and PhD., University of Minnesota, 1973) and has been a faculty member at Cornell University since January 1974. Shuler’s research is focused on biomolecular engineering and includes development of an “artificial” animal (in vitro) for testing pharmaceuticals and chemicals for toxicity, bioprocess production systems for useful compounds, such as paclitaxel from plant cell cultures, production of foreign proteins using a wide variety of genetically engineered hosts, and computer models of cells relating physiological function to genomic structure. Shuler has co-authored a popular textbook in bioprocess engineering (selected by AIChE as among 30 authors of groundbreaking chemical engineering texts). Shuler has been elected to the National Academy of Engineering and American Academy of Arts and Sciences. He has received numerous awards for research, teaching, and advising of students.

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May 20, 2009, A265 Bourns Hall daniel

Daniel Gryko, Professor, Institute of Organic Chemistry, Polish Academy of Science

Title: Corroles – From Synthesis to Photophysics

Corroles, one carbon shorter analogues of porphyrins emerged a few years ago as an independent area of research. Their coordination chemistry, photophysics, synthesis, chemical transformations, electrochemistry and other properties have recently been studied in great detail. Since initial reports by Gross and Paolesse revealing one-pot syntheses of meso-substituted corroles from aldehydes and pyrrole, numerous other methods were developed. As a result yields were improved to 30-55%. A broad view on dramatic progress which occurred in recent years in the methodology of corroles synthesis will be presented. In the last two years we proved that corrole dyads and triads can be synthesized in an elegant way. We combined corroles with such photoactive chromophores like: acridines, coumarines, naphthaleneimides, perylenebisimides, fullerenes and porphyrins. These systems represent an important progress in photoactive multi-component structures: a) they contain a new, easily available tetrapyrrolic chromophore with good photochemical properties, b) they have clearly overcome the previously reported instability of free-base corroles; c) the properties here reported can favorably compare with those of the most often used porphyrins-based arrays, as shown by the lifetime and yields of the CS states. Our studies confirm that free-base corroles are valuable components for the construction of artificial arrays for light energy conversion and open new possibilities for photovoltaic (light to electrical energy) and artificial photosynthetic (light to chemical energy) applications. The synthetic challenges, spectroscopy and photophysics of these systems will be presented.

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May 27, 2009, A265 Bourns Hall Karen_Christman

Karen Christman, Professor, Department of Bioengineering, UC San Diego

Title: Injectable Materials for Treating Myocardial Infarction and Heart Failure

Heart failure following a myocardial infarction (MI) continues to be the leading cause of death in the United States, and the rest of the western world. In 2009, an estimated 785,000 Americans will have a new MI, and 470,000 will have a recurrent MI. Approximately 37% of these patients will die from the MI within one year, and of those who do survive, two-thirds do not make a complete recovery. Moreover, it is currently estimated that approximately 5.7 million Americans are suffering from heart failure. Yet, the only successful treatment for end-stage heart failure remains total heart transplantation, which is plagued by limited donor hearts. These staggering statistics necessitate the development of new therapies for MI and heart failure. Biomaterial and tissue engineering approaches to myocardial repair are providing exciting new possibilities. Injectable materials are particularly attractive since they have the potential to be delivered via a minimally invasive approach, thereby requiring less recovery time and reducing the chances of infection. This talk will cover examples of older materials that have been utilized in the myocardium, as well as new biomimetic materials designed specifically for cardiac repair.

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Research in Bioengineering

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2008 UC Systemwide Bioengineering Symposium