RICK CARPENTER   Mentor:  Mark Kurth, Ph.D.  Chemistry Graduate Group (entered S 2005) Department of Chemistry BA (Chemistry, with Psychology minor), UC Davis

Optimization of Lead Molecules in Cancer Treatment. We have optimized a lead peptidomimetic that binds to alpha4-beta1 integrin, a cell surface receptor that has been found in leukemias and lymphomas. While our original lead binds to the integrin at low picomolar levels, copper-64 PET imaging studies have shown that the compound suffers from unfavorable pharmacokinetics in murine models. We hypothesized that if the urea moiety was replaced with benzimidazoles, benzoxazoles, and benzothiazoles, then these heterocyclic analogs would have comparable binding and have better clearance, since this analog will have an overall dianion charge (compared to a monoanion charge) at the pH of the kidney thereby decreasing reabsorption and improving clearance.

JENNIFER PHIPPS   Mentor:  Laura Marcu, Ph.D. Biomedical Engineering Department of Biomedical Engineering BS (2005), University of Washington

Fluorescence Lifetime Imaging Microscopy of Atherosclerotic Plaques.  Development of a fluorescence lifetime imaging microscopy (FLIM) technique that will be able to take measurements in vivo from atherosclerotic plaques, process the optical imaging data in real time, and provide physicians with an accurate diagnosis of the plaque's vulnerability to rupture.

STEPHANIE PULFORD Mentor: Cristina Davis, Ph.D. Mechanical/Aeronautic Engineering (entered F 2006) Department of Mechanical and Aeronautic BS (2001), Pennsylvania State University, Engineering (Aerospace Engineering)

Microorganism-Assisted Self-Assembly. Self-assembly of complex microscale structures is a promising method to produce scaffolding in liquid media with minimal human contact. Our research investigates the use of cells and microorganisms to provide dexterity, ordering, and fabrication material to assist the microassembly process. Applications in drug delivery devices and tissue scaffolding are anticipated.

MARY SAUNDERS   Mentor: Kit Lam, M.D., Ph.D. Comparative Pathology (entered F 2006) Division of Hematology and Oncology AB (1993), University of California, Berkeley

Discovery of Adhesion Molecules for Human Embryonic Stem Cells.  Combinatorial chemistry is an enabling technology that has been used successfully in the last 15 years for drug discovery by academia and the pharmaceutical industry.  With the advent of human embryonic stem cell (hESC) research and its potential application in tissue regeneration and the treatment of a variety of diseases, there is a need for the discovery of chemical compounds or factors that enable researchers to maintain the pluripotency of hESCs and to direct their differentiation into the desired cell types. One-bead-one-compound (OBOC) combinatorial chemistry is particularly suited for the discovery of extracellular matrix (ECM) mimics or ligands against unique cell surface receptors of stem cells. Several linear and cyclic peptide or peptidomimetic OBOC combinatorial libraries will be designed and synthesized. Ligands identified from these chemical libraries may be able to serve as artificial ECM to support stem cell attachment, growth, pluripotency maintenance, and directed differentiation using various hESC lines.  In addition, they may be used as flow cytometry probes for stem cell analysis.

PADMINI SIRISH   Mentor:  Nipavan Chiamvimonvat, M.D. Molecular, Cellular and Integrative Biology  Division of Cardiovascular Medicine BS (1997), Bangalore University (Biotechnology)

Isolation and Transplantation of Cardiac Stem Cells in a Murine Model.  A promising approach to the treatment of heart diseases can be through regenerative medicine using stem cells to recover the damaged heart. Cardiac progenitor cells may be used in the structural and functional recovery of damaged hearts and may avoid the potential shortcomings with other types of stem cells. Specifically, we hypothesizes that cardiac stem cells (CSC) existing in the heart tissue can be isolated and differentiated into cardiomyocytes. These differentiated cells will be tested for the treatment of heart ailments using a murine model with coronary artery ligation and cardiac failure. Specifically, we propose to examine the factors controlling the homing and the survival of the transplanted cells in vivo and assess the functionality of the CSCs using electrophysiological techniques including patch clamping and intracellular Ca2+ measurement. Understanding and defining the optimal conditions for the isolation, proliferation and transplantation of CSC will open new horizons for the treatment of heart diseases.

BREANNA WALLACE   Mentor:  Martha O’Donnell, Ph.D. Molecular, Cellular and Integrative Physiology Department of Physiology and Membrane  (entered F 2006)  Biology BS (2006), CSU Sacramento (Molecular Biology with a minor in Chemistry)

Processes Involved in Stimulation of Blood Brain Barrier Na-K-2Cl Cotransporter and Edema Formation during Ischemic Stroke.  Previous studies have shown that the BBB Na-K-Cl cotransporter is a major participant in ischemia-induced cerebral edema formation and is quite sensitive to stimulation by hypoxia, aglycemia and also AVP, each capable of stimulating independently of the others.  AVP stimulates the BBB Na-K-Cl cotransporter in a manner that is mediated by V1 AVP receptors and is Ca-dependent, while little is known about hypoxia and aglycemia stimluation. Breanna plans to pursue the question of how hypoxia and aglycemia stimulate the Na-K-Cl cotransporter.

TYLER WEEKS Mentor:  Thomas Huser, Ph.D. Applied Science Graduate Group (entered F 2006) Department of Internal Medicine BS (2006), Brigham Young University (Physics)

In-Vivo Vascular Flow Cytometry. Tyler plans to develop a new technique that allows for rapid analysis of individual cells in-vivo. This technique is based on the fact that even small differences in the molecular composition of cells can be detected based on their intrinsic molecular vibrations. The idea is similar to mass-spectrometry, at the cellular level, but is entirely non-invasive and non-destructive, since it relies on laser light scattering. Ultimately, he plans to develop to visualize and characterize vascular cells and lipoproteins non-invasively through the skin.

KIMBERLY BARNHOLT Molecular, Cellular, and Integrative Physiology  Graduate Group (entered F 2005) BA (Human Biology and French), Stanford University, 1997 MS (Biological Sciences), Stanford University, 2004

Interactions of lipoproteins with the vascular wall, cell and molecular imaging of lipid-membrane interactions, sex hormone regulation of atherogenesis.  Using both a cellular and clinical model, elucidate potential mechanisms behind the apparent vascular protection conferred by long-term physical activity. Understanding a molecular link may improve how exercise can be used to prevent most effectively the complications of atherosclerosis.

ASTRA I. CHANG Molecular, Cellular, and Integrative Physiology  Graduate Group (entered F 2005) BS (Honours Biology - Biotechnology option), University of Ottawa, 2003 MS (Cellular and Molecular Medicine), University of Ottawa, 2005

Identify functional, genomic, and biochemical properties of cardiac stem cells using cellular, electrophysiological, genomic, and proteomic approaches.

RACHEL DEVAY Biochemistry and Molecular Biology  Graduate Group (entered F 2004) BS (Genetics, with English minor), Texas A&M University, 2004

Molecular machines that mediate mitochondrial fusion and division and the physiological roles mitochondrial dynamics play in normal cells in human disease and apoptosis.

EDWARD A. GANIO Genetics Graduate Group (entered F 2005) BS (Chemistry), UC San Diego, 2000

Analysis of the processed involved in cardiac differentiation and their role(s) in cardiac hypertrophy and heart failure.

MICHAEL GOWER Biomedical Engineering Graduate Group (entered F 2004) BS (Chemical Engineering - special interest in Bioengineering and Life Sciences), Colorado School of Mines, 2004

Employ a systems engineering approach to examine the molecular and biophysical mechanisms by which endothelial progenitor cells are recruited in the early stages of atherosclerosis.