“Regeneration of Bone and Cartilage: A Tale of Two Tissues”

Among the many tissues in the human body bone has the highest potential for regeneration. This was first recognized by Hippocrates in ancient Greece over 24 centuries ago. Hippocrates was also the first physician to propose the concept that native endogenous natural signals are superior and safe therapeutic agents for clinical applications. Our laboratory was the first to identify, isolate and purify the signals for bone regeneration the Bone Morphogenetic Proteins (BMPs). The aim of this lecture is to describe the BMP story and illustrate three vignettes of BMP applications in the clinic. Compared to bone an adjacent tissue articular cartilage is feeble in its regenerative potential. Articular cartilage is recalcitrant to repair. In part this may be due to relatively avascular nature of the tissue, potential presence of growth inhibitors and paucity of endogenous stem cells in articular cartilage. This lack of regeneration is an unmet need in orthopaedic surgery and therefore presents a challenge and an opportunity. We will describe the current approaches including signals, stem cells and scaffolds for tissue engineering of articular cartilage. Our current research and future plans include engineering lubrication in tissue engineered articular cartilage with an eye toward the design and manufacture of a total knee joint. A. Hari Reddi is a member of the Biomedical Engineering Graduate Group and teaches Tissue Engineering to students in the BMEGG.

When: Thursday 4/17/12 4:10 PM

Where: 1005 GBSF

“A tale of two rhodopsins: key roles of ionization in trans-membrane signaling”

Trans-membrane proteins convert extra-cellular stimulation to intra-celluar signaling. In bacteriorhodopsin, opening of the proton uptake channel is a key event leading to the robust vectorial transportation of protons from cytosol. By molecular dynamics simulation, we show that D96, a key residue and a proton donor, plays crucial roles in this process. The simulations indicate that the proton uptake channel remains closed when D96 is protonated and opens quickly when D96 is  deprotonated, making it possible for D96 to re-capture a proton from water molecules. In bovine rhodopsin, a G-protein coupled receptor, stability of the crucial ion-lock is examined through molecular dynamics simulations. Here, we illustrate that the ion-lock has been designed such that the conformational change of retinal would disrupt the ion-lock and trigger the subsequence conformational changes on the cytoplasmic side of the protein that eventually leads to the binding of the G-protein.

When: 5/10/12 4:10 PM

Where: 1005 GBSF

Deirdre R. Meldrum Arizona State University Senior Scientist Professor of Electrical Engineering Director of the Biosignature Initiative Director of the Center for Biosignatures Discovery Automation in the Biodesign Institute PI/Director of the NIH Center of Excellence in Genomic Sciences: Microscale Life Sciences Center

“Biosignatures Automation for Improved Human Health”

Everyone has the goal of living a long, healthy life. Our society aspires to chronic health. Biosignatures would enable a health care system that focuses on keeping healthy people healthy and reducing the time sick people spend in hospitals and in clinical care. The goal is to enable the prediction of disease risk and the prevention of disease, with pre-symptomatic diagnosis and interventional therapeutic treatment of individuals based upon their personal biosignature – all the information about an individual (genomic, proteomic, cellomic, imaging, behavior, and other information) that enables prediction of disease predisposition and future health status. This presentation will address the key challenges required to discover and implement biosignatures in a nation-wide health care program. Specifics will be provided on single cell biosignatures including the quantification of physiological and morphological manifestation of underlying gene and protein alterations with disease. Examples will be provided with lung cancer, esophageal cancer, and breast cancer. Successful implementation of biosignatures in a nation-wide health care program will require high-throughput automation for biosignature discovery, clinical validation, standardization, and qualification for use in pre-symptomatic diagnoses, drug development research, commercialization, and patient management for healthy patient outcomes.

Thursday, May 3, 2012 4-5 p.m.
Kemper Hall 1065

“The Influence of Mechanical and Biological Factors on Bone Formation, Repair and Adaptation”

For more than 100 years, investigators have postulated and provided experimental evidence that local mechanical conditions may substantially influence the geometry, morphology and structural integrity of bone.  While past and continuing studies have advanced our understanding of the mechano-responsiveness of bone, the impact of these mechanical factors on bone metabolic behavior and the mechanisms associated with their actions remain unclear.  What has been clear is that successful strategies for treating or preventing a large number of skeletal clinical conditions may be associated with understanding and even harnessing biomechano-regulation of bone.  The purpose of this presentation will be to provide the results of a series of experiments designed to elucidate the role of mechanical factors of bone formation, repair and adaptation.

In an effort to quantitatively study the influence of local mechanical as well as biologic factors on bone behavior, we utilized several novel in vivo models in which both mechanical and biologic environments were experimentally controlled.  Using a hierarchical perspective, the studies were focused on establishing linkages between boundary conditions at the organ or whole bone level and the cellular and molecular regulation associated with the mechano sensation and response.  The results of these studies demonstrated that mechanical forces play an important epigenetic role in regulating the shape and morphology of bone structure.  Newly regenerated bone is particularly sensitive to applied mechanical conditions, which trigger biologic signaling cascades that are similar to those observed in response to biologic stimulating factors.  Migration, proliferation and differentiation of progenitor cells responsible for the repair of bone appear to be sensitive to local mechanical factors and the repair of accumulated micro-damage in bone tissue may require mechanical stimulation.  Furthermore, many or all of these conditions may be influenced by age.  Taken together, these studies have provided valuable insight into the critical interactions between mechanically and biologically mediated regulation of bone and subsequently have provided direction for clinical interventional strategies.

Dr. Goldstein joined the faculty at the University of Michigan in the Section of Orthopaedic Surgery in 1981, and was promoted to Assistant Professor on tenure track in 1983.  During the next number of years he rose through the academic ranks, including promotion to Associate Professor with tenure, followed by Full Professor in the Department of Surgery, eventually being changed to the Department of Orthopaedic Surgery during its “split” from the Department of Surgery.  In addition to appointments in the Medical School, he also was granted joint appointments in the College of Engineering where he currently holds the titles of Professor of Mechanical Engineering as well as Professor of Biomedical Engineering.  In 1998 he was awarded the Henry Ruppenthal Family Professorship of Orthopaedic Surgery and Bioengineering, the first endowed chair available to the Department of Orthopaedic Surgery.

When: 4/3/12 4:00 PM
Where: 1005 GBSF

Nicholas Kenyon

“Nitric oxide at the interface of therapeutics and biomarkers in asthma”

Asthma is one of the most common diseases in the world. New biomarkers and new therapies that can help in managing and treating this disease are sorely needed. Exhaled breath nitric oxide concentration is an increasingly used biomarker in asthma. We have been investigating whether drugs that potentially manipulate lung nitric oxide levels, either L-arginine or arginase inhibitors, could prove to be effective treatments for patients with asthma.

When:  Thurs. 4/26/12 4:10 PM

Where: 1005 GBSF

Rebecca Richards-Kortum

Dr. Rebecca Richards-Kortum, Ph.D.

Stanley C. Moore Professor of Bioengineering

Professor of Electrical and Computer Engineering

Founder of Beyond Traditional Borders

Director of Rice 360°: Institute for Global Health Technology

Optical Spectroscopy and Imaging Laboratory

Ph.D., Medical Physics, Massachusetts Institute of Technology (1990)

M.S., Physics, Massachusetts Institute of Technology (1987)

B.S., Physics and Mathematics, University of Nebraska – Lincoln (1985)

“Engineering the Future of Health Care: Low-Cost, High Performance Technologies for Global Health”

Abstract:

Medical technologies have revolutionized healthcare in every setting in which they are available.  Unfortunately, technologies are often not available where they are needed most.  The lives of nearly 4 million African women, newborns, and children could be saved if already well-known interventions reached 90% of families.  While the demand for appropriate health technologies is enormous, traditional market incentives have failed to inspire effective solutions.  The “modern development enterprise” requires a new model of technology development if it is to succeed.   This talk will describe a framework to develop the next generation health care delivery system for use in low-resource settings. Case studies illustrating the innovation, evaluation and scale-up of high-performance, low-cost technologies will be presented with a focus on: maternal and neonatal health.

Download Flyer Here

Lecture will be webcast live here:http://ustre.am/Isll

Bio

For two decades, Rebecca Richards-Kortum has focused on translating research that integrates advances in nanotechnology and molecular imaging with microfabrication technologies to develop optical imaging systems that are inexpensive, portable, and provide point-of-care diagnosis. This basic and translational research is highly collaborative and has led to new technologies to improve the early detection of cancers and other diseases, especially in impoverished settings.

Microelectromechanical systems (MEMS) use micro-scale technology to design low-cost, reusable platforms for point-of-care (POC) diagnostics. When used with contrast agents, these rugged and portable optical imaging systems detect molecular signatures of pre-cancer, assess tumor margins, and monitor a patient’s response to therapy. Current systems are being tested and applied through multidisciplinary collaborations with clinicians and researchers at Rice, the UT M.D. Anderson Cancer Center, UT Health Science Center-Houston, UT at Austin, the University of Arizona, and the British Columbia Cancer Agency. Over the past few years, Richards-Kortum and collaborators have translated these technologies from North America to both low- and medium-resource developing countries (Botswana, India, Taiwan, Mexico, and Brazil).

Richards-Kortum’s research has led to the development of 26 patents and more than 210 refereed research papers. Her teaching programs, research and collaborations have been supported by generous grants from the National Cancer Institute, National Institutes of Health, National Science Foundation, U.S. Department of Defense, Howard Hughes Medical Institute, Bill & Melinda Gates Foundation, Whitaker Foundation, and the Virginia and L.E. Simmons Family Foundation.

Richards-Kortum is a Fellow of the American Institute for Medical and Biological Engineering (2000), and the recipient of the Presidential Young Investigator (1991) and Presidential Faculty Fellow (1992) awards from the National Science Foundation; and the Becton Dickinson Career Achievement Award from the Association for the Advancement of Medical Instrumentation (1992). She has been named a Howard Hughes Medical Institute (HHMI) Professor (2002); received the Sharon Keillor Award for Women in Engineering Education (2004) and Chester F. Carlson Award (2007) from the American Society for Engineering Education. She served on the inaugural National Advisory Council for Biomedical Imaging and Bioengineering for the National Institutes of Health (2002-2007), was elected Fellow of the American Association for the Advancement of Science and Biomedical Engineering Society (2008); and received the Vice President Recognition Award by IEEE (2008). In 2008, she was inducted into the National Academy of Engineering, and is a committee member of the National Academies Committee on Conceptual Framework for New Science Education Standards (2010-2012). Recently, she was named the Pritzker Distinguished Scientist and Lecturer of the Biomedical Engineering Society 2010 Annual Meeting, and was given the Celebrating Women in Science Award by BioHouston, Inc. (2011).

When: Friday 4/20/12 4:00 PM

Where: 1005 GBSF

]]> http://www.bme.ucdavis.edu/articles/2012/04/08/maroney-bryan-distinguished-lecture-rebecca-richards-kortum/feed/ 0 http://www.bme.ucdavis.edu/articles/2012/04/05/distinguished-seminar-martine-laberge-clemson/ http://www.bme.ucdavis.edu/articles/2012/04/05/distinguished-seminar-martine-laberge-clemson/#comments Fri, 06 Apr 2012 06:59:58 +0000 Holly Ober http://www.bme.ucdavis.edu/?p=4462

Martine LaBerge, Ph.D.

“TOTAL KNEE REPLACEMENT: A PLATFORM FOR EDUCATION, RESEARCH, AND ECONOMIC DEVELOPMENT”

Over the past two decades, the field of biomedical engineering has assumed a leadership position in technology innovation and has been a driver for knowledge based economic development. This is largely due to the impact of academic institutions nationwide that have provided an ideal environment to stimulate innovation, discovery, dissemination, and entrepreneurship. In fact, faculty driven research programs are often the catalyst for such initiatives. This presentation will focus on the impact of total knee replacement research as a platform for education, training, discovery, and entrepreneurship. Even though total knee arthroplasty is a routine orthopaedic procedure that significantly impacts the quality of life of millions of patients through design optimization, these implants fail as they are compromised by overuse and harsh environmental and mechanical conditions. At Clemson University, addressing the failure of these implants from a bioengineering perspective has led to the discovery of new knee joint simulator lubricants and phospholipid-based viscosupplementation device, the design of tribological testing and measuring equipment and methods including dynamic contact pressure sensors, and the synthesis of new bearing materials and drug delivery systems. This presentation will illustrate these technologies and how such research program can serve as a platform for the training of graduate students, state legislation advocacy, and major program development.

Martine LaBerge is Professor and Chair of Bioengineering at Clemson University which she joined in 1990 as Assistant Professor of Bioengineering, following MS and PhD degrees in Biomedical Engineering at the University of Montreal, and post-doctorate in Mechanical Engineering at the University of Waterloo. She has published numerous publications on the evaluation and characterization of natural and artificial surfaces used in the design of orthopaedic and vascular implants and is an inventor on several licensed patents. She received the South Carolina Governor’s Award for Scientific Awareness for the development of major programs in the state. She is a Fellow of the American Institute for Medical and Biological Engineering and Fellow, Biomaterials Science and Engineering of the International Union of Societies for Biomaterials Science and Engineering. She is a board member of the Biomedical Engineering Society and the Associate Editor for orthopaedics of the Journal of Biomedical Materials Research – Applied Biomaterials. She is a past-President of the Society For Biomaterials and is the recipient of its inaugural Service Award.

Donald Bers

Cardiac CaMKII signaling in heart failure, arrhythmias and transcriptional regulation: Imaging and Modeling

CaMKII regulates many processes in cardiac myocytes. We used FRET-based sensors to measure dynamic beat-to-beat changes in [Ca-CaM] in intact myocytes and mathematical models of CaMKII activation in different cellular domains. CaMKII has acute effects on numerous cardiac ion channels (e.g. Ca, Na, K and ryanodine receptor, RyR causing Ca sparks & waves) and CaMKII expression and activity is enhanced in heart failure (HF). How do CaMKII effects integrate at the myocyte level to influence cardiac action potential (AP) and arrhythmias? CaMKII-dependent effects on Na current phenocopy a human mutation that causes combined long-QT and Brugada syndromes in patients. CaMKII also mediates Ca current facilitation, and other ion channel effects than can be arrhythmogenic. CaM, calcineurin and CaMKII are also involved in nuclear transcriptional regulation in pathways that involve histone deacetylases (HDAC) and NFAT, and these may contribute to the development of cardiac hypertrophy, failure and arrhythmias. HDAC5 binds to MEF2 and suppresses MEF2-driven transcription, whereas HDAC5 nuclear export relieves this and thereby activates hypertrophic gene transcription. Remarkably, this Ca-dependent pathway is insensitive to global Ca transients at each heartbeat, and is functionally insulated from Ca involved in EC coupling. Thus myocytes can distinguish simultaneous local and global Ca signals involved in contractile activation from those targeting gene expression. Thus Ca and CaMKII signaling in cardiac myocytes can mediate many acute effects (in seconds to hours) that influence cardiac electrophysiology and contractile function, and also on a longer time scale (tens of minutes to days) to influence gene expression and contribute to cellular and molecular remodeling.

When: Thursday, April 5, 2012  4:10 PM

Where: 1005 GBSF