Associate Professor of Medicine
Chief of Endocrinology, Metabolism and Molecular Medicine
Feinberg School of Medicine
Associate Professor of Neurobiology and Physiology
Weinberg College of Arts and Sciences
The focus of Dr. Joe Bass’ research is on insulin signaling and the neuroendocrine regulation of body weight and energy balance. His approach integrates cell biological and genetic strategies, with an emphasis on gene targeting and chemical mutagenesis in the mouse. Previous studies have identified over 60 mutations in the insulin receptor gene (IR) in families with congenital insulin resistance, a monogenic subtype of type 2 diabetes mellitus. Surprisingly, even first degree relatives with identical IR mutations show differences in disease onset and in the severity of secondary complications. To better understand the pathobiology of this disorder, and because IR null mutations are lethal, Dr. Bass’ laboratory is producing two insulin receptor knock-in animals to introduce mutations that they originally identified in a young woman with congenital insulin into the germline of the mouse. The allele series produced by these IR mutant animals will shed light on the role of insulin receptor signaling during early differentiation, during development and in the progression of type 2 diabetes. Genetic models in the mouse have also enabled them to make the exciting discovery that the transcription network at the core of the endogenous biological clock also regulates feeding and metabolism. We will address how altered clock gene function results in metabolic disease using behavioral, metabolic and molecular analyses in the Clock mutant mouse and in other conditional and multi-tissue knock-out models. Finally, through collaboration with the Center on Functional Genomics, Dr. Bass’ lab has initiated a phenotype-based screen for diabetes-causing genes in the mouse.