COBRE
UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER
Promising Junior Investigators
Xin "Sarah" Zhang, MD; Scott M. Plafker, PhD; Zhonglin Xie, MD, PhD; Timothy J. Lyons, MD - Co-PI;Kevin R. Short, PhD; Diane M. Warren, PhD; Jian-xing Ma, MD, PhD - PI
Project 1: “Impact of Age and Exercise on Insulin Action”
PJI: Kevin R. Short, PhD Mentors: Kenneth C. Copeland, MD and Andrew Gardner, PhD
Kevin Short, PhD obtained graduate training in human exercise physiology, metabolism and muscle biochemistry at Purdue University and Ball State University. He then completed post-doctoral work in endocrinology, diabetes, and aging at Mayo Clinic, before joining the faculty of the Mayo School of Medicine for four years. At Mayo his work focused on changes muscle mitochondrial metabolism in response to aging, exercise training, diabetes and insulin. Dr. Short developed expertise in measuring energy expenditure, protein and glucose metabolism with stable isotope-labeled tracers and tissue biochemistry in humans and animals. This work resulted in more than 30 publications, including several significant original papers in top-tier journals. In 2006 Dr. Short accepted a tenure-track position within the Department of Pediatrics in the Section of Endocrinology and Diabetes. His goal is to establish a metabolic research laboratory with tools to measure human energy expenditure, protein and glucose metabolism, and markers of diabetes complications in pediatric and elderly populations. Resources for salary and laboratory support are available from the Department of Pediatrics and through the Children’s Metabolic Research Institute. In addition to funding through this CoBRE award Dr. Short will seek extramural funding for start-up projects that will lead on to more significant independent support. Dr. Short has received previous independent funding from the American Federation of Aging Research. The goals of Dr. Short’s CoBRE project are to, 1) establish a method of measuring insulin action in children and adults following a meal, and 2) examine how insulin action is affected by exercise training in children versus young and elderly adults. These studies build upon previous work in older people by Dr. Short and his colleagues. Since his prior experience with research in children is limited, Dr. Short will be closely mentored by Ken Copeland, MD, Section Chief of Endocrinology and Diabetes in the Department of Pediatrics. Dr. Short will receive additional assistance from Andrew Gardner, PhD, for studies on exercise training and cardiovascular effects, particularly in older people. Both mentors have extensive research and clinical experience in their respective areas.
Project 2: "Activation of AMPK protests against diabetic vascular complications"
PJI: Zhonglin Xie, MD, PhD Mentor: Ming-Hui Zou, MD, PhD
Zhonglin Xie, MD, PhD is an Assistant Professor (tenure track) in the Department of Medicine, Section of Endocrinology, the Oklahoma University Health Sciences Center. He received his Ph D. in Hokkaido University, Japan, and had an outstanding postdoctoral research experience in Boston University and University of Tennessee, during this period he was supported by a postdoctoral fellowship from the American Heart Association. Dr. Xie is very productive with over 40 publications, including 12 since 2001 in high impact journals such as Circulation Research, Diabetes, J Biol Chem, Hypertension, Atherosclerosis, Thrombosis, and Vascular Biology. He has made the important discovery that protein kinase C- zeta regulates LKB1-AMPK cascade by increased LKB1 phosphorylation at Ser 428 and Ser 307, the latter being a newly identified phosphorylated site. His expertise in molecular biology and physiology will be applied to independent studies on the mechanisms by which AMPK activation protects against vascular complications in diabetes. His studies will yield novel information of how AMPK is regulated in diabetes and if AMPK is a therapeutic target in preventing or delaying vascular complications in diabetes.
Project 3: "Genetic and environmental contributions to diabetes in Oklahoma American Indians"
PJI: Diane M. Warren, PhD Mentors: Morris W. Foster, PhD and John Mulvihill, MD; Consultant, Laura Almasy, PhD
Diane Warren, PhD is an Assistant Professor in the Department of Anthropology of the University of Oklahoma. A biological anthropologist, she joined the OU faculty following a postdoctoral appointment in the Department of Genetics of the Southwest Foundation for Biomedical Research in San Antonio. At SFBR, Dr. Warren worked closely with Dr. Laura Almasy, an expert in the field of statistical genetics and a developer of SOLAR, an important software used in variance components-based analyses of data from families. Dr. Almasy will serve as a consultant to the proposed project. The focus of Dr. Warren's research at SFBR was quantitative genetic, linkage, association, and other statistical genetic analyses of complex disease phenotypes. Her research included an investigation of correlations between type 2 diabetes and hemostasis-related phenotypes. In her CoBRE application, Dr. Warren proposes to use a variance components-based approach applied to data from American Indian sib pairs to investigate the contribution of genetic, environmental, and genotype-by-environment interaction effects to variation in quantitative risk factors for type 2 diabetes. Dr. Warren will be mentored closely by Dr. Morris Foster, an anthropologist with extensive experience with research involving American Indians in Oklahoma as well as with genetic research in American Indian communities. Type 2 diabetes is a major public health concern in American Indian communities, and the results of Dr. Warren's proposed project are of potential use in the development of culturally-appropriate treatment and intervention strategies.
Project 4: "Regulation of oxidative stress and inflammation in diabetic retinopathy"
PJI: Sarah Zhang, MD Mentors: Jian-xing Ma, MD, PhD, and Timothy J Lyons, MD
Sarah Zhang, M.D. is a well-trained ophthalmologist with strong background in basic science research. She has received her Ph.D. training in China and an outstanding postdoctoral training with Dr. Jian-xing Ma, an exceptional molecular biologist in diabetes and vision research. The combination of her extensive experience in both the clinical and basic research makes Dr. Zhang an ideal candidate for independent investigator in diabetes and vision field. In nearly 10 years, she has published 42 peer-reviewed scientific articles and co-authored several review articles and book chapters. She is the first to study the anti-permeability effect of angiogenic inhibitors in diabetic retinopathy and the first to identify the novel function of pigment epithelium-derived factor (PEDF) as an endogenous anti-inflammatory factor. Her excellent work led her to be appointed as an Assistant Research Professor early this year. Recently, she has been promoted as an Assistant Professor of Medicine (tenure track). In her independent research project, Dr. Zhang will study the inhibitory effects of PEDF on oxidation, which is proposed as a central unifying mechanism for the PEDF activities of anti-inflammation, anti-permeability and neuroprotection. This unifying mechanism may explain the complex activities of PEDF in the vascular system and in retinal neurons. The success of this proposal will reveal a novel endogenous protective system in diabetic retina, and thus, identify a new pathogenic mechanism for diabetic retinopathy.
Project 5: "Diabetes and the multitude of pathophysiological consequences associated with this disease state have reached epidemic proportions in the United States"
PJI: Scott M. Plafker, Ph.D., Mentor: Luke Szweda, Ph.D.
Scott M. Plafker, Ph.D. received his Ph.D. from the Johns Hopkins University School of Medicine in molecular virology in the laboratory of Dr. Wade Gibson. He then did post-doctoral studies in the laboratory of Dr. Ian Macara in The Center for Cell Signaling at the University of Virginia. In Dr. Macara’s laboratory, he gained extensive experience in the field of nuclear transport and discovered a novel mechanism by which some ubiquitin pathway enzymes are imported into the nucleus. The publication of this novel mechanism in the Journal of Cell Biology was well received as reflected by its review in both Developmental Cell and Nature Cell Biology. In October of 2003, Dr. Plafker joined the Dept. of Cell Biology at the University of Oklahoma Health Sciences Center as a tenure-track Assistant Professor. His laboratory is intensively focused on defining the functional roles for different ubiquitin pathway enzymes during normal and stress states as well as during embryonic development. They currently employ a broad range of techniques and experimental systems ranging from mammalian tissue culture to the Danio rerio (zebrafish) animal model. Recently, Dr. Plafker‘s efforts have been directed towards understanding how two partner ubiquitin enzymes (UBE2E3 and RCBTB1) regulate the angiotensin II receptor during hyperglycemia. His transition into the study of ubiquitin in diabetes will be greatly facilitated by his mentor, Dr. Luke Szweda. Dr. Szweda is an Associate Member in the Free Radical Biology and Aging Research Program at the Oklahoma Medical Research Foundation (OMRF) and holds an adjunct appointment in the OUHSC Dept. of Medicine, Section of Endocrinology and Diabetes. He is a leader in the field of oxidative stress and has extensive experience using biochemical and physiological approaches to define the redox signaling mechanisms induced by diabetes. His advice and assistance with the signaling and animal studies of Dr. Plafker’s proposal will provide an ideal foundation for promoting Dr. Plafker’s development as an independent, R01-funded investigator.