I am a physician-scientist, who has been seeing patients with endocrine disorders and diabetes while engaging in diabetes and metabolism related research for the last 15 years. My work was involved various aspects of diabetes including insulin resistance, islet biology, islet neogenesis, adipogenesis, mitochondrial metabolism and circadian biology as relates to metabolic disease. In my lab, we address various questions
related to islet neogenesis, β-cell compensation and secretory function, circadian control of islet function, mitochondrial control of metabolic processes using various knockout and transgenic mouse models, along with ex vivo and in vitro models to dissect the regulatory molecular mechanisms underlying islet dysfunction in diabetes. We have developed a novel technique of in vivo islet neogenesis coupled with engineering these neo-islets with expression of PD-L1, an inhibitor of co-stimulation to achieve protection of these neo-islets from autoimmune destruction rendering these treated diabetic NOD mice cured of diabetes.
The broad goal of my laboratory is discovering regulatory mechanisms that control β-cell proliferation, function and development and their application to prevention and therapy of diabetes. We are working on understanding the mechanisms underlying regulation of functional β-cell mass in a VA ORD funded project, specifically looking at the mechano-sensing hippo-Tead1 pathway in β-cells. My lab has been working over the last few years on circadian control of islet function. In these NIDDK-R01 and ADA funded projects we have demonstrated that disruption of the molecular clock Bmal1-null islets develops impaired stimulus-secretion coupling and β-cell failure. We demonstrated for the first time that Bmal1 and the β-cell clock regulate β-cell mitochondrial OXPHOS and oxidative stress via regulation of Nrf2.
I moved 2 years ago to the University of Pittsburgh as the Director of the Diabetes and Beta Cell Biology Center and in this capacity, I am building a metabolism oriented integrated physiology program that seeks to decipher the mechanistic basis of diabetes, obesity and metabolic disorders, with a goal to prevent, treat and cure diabetes. In my capacity as a Physician-Scientist who actively takes care of patients with diabetes, I am expanding a collaborative Diabetes Research program with a strong translational component. We have started a program to generate iPS cell-derived islet/beta cells that would physiologically respond to glucose to secrete insulin that are engineered to resist autoimmune destruction. The longer-term goal is to translate these models into patient-specific therapy to cure diabetes, both Type1 and Type 2.