Date

Distinguished Speaker

Title

Professor 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.

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

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).

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

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.

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

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).

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

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.

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

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 (Sin, et al., Biotechnol. Prog. 20:385, 2004; Khamsi, Nature 435:12, 2005).

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 an unexpected synergistic response to certain drug combinations not observable in traditional assay systems. 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 and response to pharmaceuticals.

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.