Rupangi Vasavada, PhD
- Associate Professor of Medicine (Endocrinology, Diabetes and Bone Disease)
Research Topics:Apoptosis/Cell Death, Diabetes, Growth, Growth Factors and Receptors, Insulin, Knockout Mice, Receptors, Regeneration, Signal Transduction, Transgenic Mice, Transplantation
Diabetes, a major metabolic disease, affects ~10% of the US population, with an expected growth rate of 20-33% by 2050, according to the CDC, causing one of the highest life expectancy and economic tolls to the health system. All forms of diabetes ultimately result from the loss of functional pancreatic beta cells that produce insulin. It is now known that even patients with long-term diabetes retain residual beta cells with the potential to proliferate and regenerate. Therefore, enhancing a patient’s own functional beta cell mass, through improved function, survival and/or proliferation of existing beta cells, or through the formation of new beta cells from precursor cells, represent potential future therapeutic approaches for the treatment of diabetes.
My lab has been interested in understanding the pathways and mechanisms that regulate beta cell growth, survival and function, with the ultimate objective being to enhance regeneration of functional beta cells in vivo. We have focused on the role of specific growth factors, parathyroid hormone-related protein (PTHrP), lactogens, and more recently, osteporotegerin (OPG), in normal beta cell physiology. We use transgenic overexpression as well as conditional knockout mouse models to determine the in vivo effects of these growth factors and their downstream signaling and molecular pathways on beta cell proliferation, survival and function.
The ultimate objective of our research is to find ways to enhance preservation and regeneration of functional beta cells in vivo, for the treatment of diabetes. There are several approaches we have taken towards this therapeutic goal. 1) To test the effects of acute and systemic administration of molecules in rodent models of depleted beta cell mass and in the pathophysiological settings of type 1 and type 2 diabetes. 2) To assess the effects of these molecules on human beta cells in vitro, and in vivo, in rodent models of islet transplantation. 3) More recently, we have focused attention on discovering ways to quantify human beta cell proliferation in collaboration with Dr. Garcia-Ocana. The currently used methods can label dividing cells but have not convincingly demonstrated an increase in beta cell numbers. As the ultimate goal in the treatment of diabetes is to increase human beta cell mass, we are developing a novel labeling tool to address this problem.
This work is currently funded by the NIH/NIDDK, and the Juvenile Diabetes Research Foundation.For a complete list of my publications, please visit the following link: http://www.ncbi.nlm.nih.gov/sites/myncbi/rupangi.vasavada.1/bibliography/41142260/public/?sort=date&direction=ascending
Multi-Disciplinary Training AreaBiophysics and Systems Pharmacology [BSP]
BS, University of New Delhi
MS, University of New Delhi
PhD, University of Pennsylvania
A U.S. utility patent No. 9333239, issued on 5/10/2016, for “Use of Osteoprotegerin (OPG) to increase human pancreatic beta cell survival and proliferation”
Mozar A, Lin H, Williams K, Chin C, Li R, Kondegowda NG, Stewart AF, Garcia-Ocaña A, Vasavada RC. Parathyroid Hormone-Related Peptide (1-36) Enhances Beta Cell Regeneration and Increases Beta Cell Mass in a Mouse Model of Partial Pancreatectomy. PloS one 2016 Jul; 11(7).
Kondegowda NG, Fenutria R, Pollack IR, Orthofer M, Garcia-Ocaña A, Penninger JM, Vasavada RC. Osteoprotegerin and Denosumab Stimulate Human Beta Cell Proliferation through Inhibition of the Receptor Activator of NF-κB Ligand Pathway. Cell metabolism 2015 Jun;.
Stewart AF, Hussain MA, García-Ocaña A, Vasavada RC, Bhushan A, Bernal-Mizrachi E, Kulkarni RN. Human β-Cell Proliferation and Intracellular Signaling: Part 3. Diabetes 2015 Jun; 64(6).
Wang P, Fiaschi-Taesch NM, Vasavada RC, Scott DK, García-Ocaña A, Stewart AF. Diabetes mellitus-advances and challenges in human β-cell proliferation. Nature reviews. Endocrinology 2015 Feb;.
The role of PTHrP in pancreatic beta cells and implications for diabetes pathophysiology and treatment. Clinical Reviews in Bone and Mineral Metabolism 2014; 12: 165-177.
Kondegowda NG, Mozar A, Chin C, Otero A, Garcia-Ocaña A, Vasavada RC. Lactogens protect rodent and human beta cells against glucolipotoxicity-induced cell death through Janus kinase-2 (JAK2)/signal transducer and activator of transcription-5 (STAT5) signalling. Diabetologia 2012 Jun; 55(6).
Williams K, Abanquah D, Joshi-Gokhale S, Otero A, Lin H, Guthalu NK, Zhang X, Mozar A, Bisello A, Stewart AF, Garcia-Ocaña A, Vasavada RC. Systemic and acute administration of parathyroid hormone-related peptide(1-36) stimulates endogenous beta cell proliferation while preserving function in adult mice. Diabetologia 2011 Nov; 54(11).
Guthalu Kondegowda N, Joshi-Gokhale S, Harb G, Williams K, Zhang XY, Takane KK, Zhang P, Scott DK, Stewart AF, Garcia-Ocaña A, Vasavada RC. Parathyroid hormone-related protein enhances human ß-cell proliferation and function with associated induction of cyclin-dependent kinase 2 and cyclin E expression. Diabetes 2010 Dec; 59(12).