“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

Tingrui Pan and Kyriacos Athanasiou visited the College of Biomedical Engineering and Instrument Science (CBEIS) and School of Medicine, at Zhejiang University (Hangzhou, China) between March 28 and 29.  They formally established an education exchange program with CBEIS on the GREAT Curriculum in Advanced Research and Education (CARE) Program.  The CARE program was launched this Spring. Four excellent junior students from CBEIS have joined our department to study our minor curriculum along with our BME students.

Steve Ho

Steve Ho, a graduate student in the Leach Lab, has received a Whitaker International Fellowship to do research next summer (2013) at the Institute for Biomechanics at the  Swiss Federal Institute of Technology Zurich (ETHZ). At the Institute for Biomechanics, he will be in the Skeletal Tissue Engineering Group working under Professor Ralph Müller and Dr. Sandra Hofmann. Steve’s project involves customizing an advanced bioreactor with a flow sensor to be able to continuously adjust fluid flow rate in order to maintain a constant optimal shear stress felt by mesenchymal stem cells seeded on a silk fibroin scaffold.

Sonja Fenske

Sonja Fenske, a UC Davis biomedical engineering major, has received a Whitaker International Fellows Scholarship for a Master’s degree in Biomedical Engineering at the Imperial College, London.  Sonja plans on taking the Neurotechnology stream.  Her course of study will cover the development of new technology for the investigation of brain function with focus on the application of this knowledge to improve technology of wider benefit to society. Examples of work done in this field included the development of neuroprosthetic devices, new neuroimaging approaches, central nervous system drug discovery and robotic assistive devices for helping those with central nervous system disorders. Neurotechnology is in a rapid phase of growth internationally and is of strategic importance for the medical device and pharmaceutical industries.