 Assistant Professor of Medicine
Medical School
The Medical College of Pennsylvania (MD/PhD)
Residency
Rush-Presbyterian St. Lukes' Medical Center, IL
Endocrine Fellowships
University of Chicago Medical School, IL
Board Certified
American Board of Internal Medicine 1994;
Endocrinology and Metabolism 1997 Cell and Molecular Regulation of Body Weight, Feeding and Metabolism The focus of our research is on insulin signaling and the neuroendocrine regulation of body weight and energy balance. We are using a combination of genetic and cell biological approaches to investigate the molecular basis of obesity and diabetes, two rising epidemics in the US. In studies based on our analysis of humans with congenital insulin resistance, an inherited subtype of diabetes, we have identified new missense mutations in the insulin receptor gene (IR). Studies at a cellular level have translated our analysis of these patients into fundamental new knowledge on IR trafficking and degradation. Our current hope is that this in depth insight into IR metabolism might enable new therapeutic strategies to improve insulin receptor expression and function. To fully understand the basis of human congenital insulin resistance, we have also begun to produce an allele series modeling mutations identified in our studies of human subjects with type 2 diabetes. These new IR knock-in animals will enable studies of the role of insulin signaling in early development and over time during aging in multiple tissues involved in glucose metabolism. We have also recently made the exciting discovery that the circadian gene network that functions as the core of the endogenous biological clock also regulates feeding and metabolism. A major question is whether alteration of clock gene function within the brain or within peripheral tissues results in metabolic disease? We are using behavioral, metabolic and molecular analyses to test various hypotheses that will delineate the relationship between circadian and metabolic pathways. Research Topics Cell mechanisms of insulin sensitivity and kinase regulation Genetic models of type 2 diabetes Regulation of body weight and metabolism by the circadian gene transcription network.
Selected Publications |
