Rohit N. Kulkarni


Department of Cell Biology
Joslin Diabetes Center
One Joslin Place, Room 602
Boston, MA 02215
Tel: (617) 713-3460
Fax: (617) 713-3476
Email: rohit.kulkarni@joslin.harvard.edu
6 postdoctoral fellows, 3 research assistants

 

My laboratory is focused on the following areas:

 

PROGENITORS/STEM CELLS & INDUCED PLURIPOTENT STEM CELLS IN THE REGENERATION OF ISLET CELLS: Our studies indicate the presence of potential stem cells/progenitors within the islet that may play a role in the regeneration of beta cells in the adult organism. Several approaches including lineage trace analyses, transplantation, and parabiosis are being undertaken in genetically engineered mice to address this possibility. A related area of research focuses on understanding the pathways that modulate the life cycle of ß- and a-cells. In addition we are also focusing on the derivation of induced pluripotent stem (iPS) cells from skin biopsies of patients with type 1, type 2 diabetes and obese patients with the long-term aim of differentiating the iPS cells into functional insulin and glucagon producing cells.

 

GROWTH FACTOR CONTROL OF BETA  AND ALPHA CELL REPLICATION AND APOPTOSIS. Several studies, including our own, suggest that growth factors, especially insulin and IGF-I signaling, play crucial roles in modulating islet function by regulating glucose sensing, cell cycle control, protecting against beta cell death and in regulating transcription factors. Using Cre-LoxP and FLP/Frt techniques, we have created genetic models to examine the roles of insulin and IGF-1 receptors and proteins in their signaling pathway in islet biology. These in vivo models complement in vitro models including primary islets from humans and rodents, and beta cell lines derived from the knockouts. Using these powerful and unique reagents we are dissecting cross-talk between growth factor and glucose signaling pathways in islet cells. A major effort is being directed towards evaluating specificity of insulin versus IGF-I signaling in beta-cell growth, apoptosis (ER stress) and cell cycle control. Together, these studies will provide critical information in several ways - first, it will allow us to develop therapeutic strategies to prevent beta cell death and to examine alternative approaches to generate new beta cells for countering type 1 diabetes. Second, these studies will open new avenues to prevent beta cell failure in type 2 diabetes.

 

MECHANISMS THAT UNDERLIE DEVELOPMENT OF DIABETES IN OBESITY. Although the high incidence of type 2 diabetes in obese individuals is well documented, the mechanisms that promote islet dysfunction in these individuals are not understood. We propose a potential link between leptin signaling and insulin/IGF-I regulated pathways that can modulate glucose signaling, at the level of the islet, and participate in mechanisms that regulate islet function and growth. This hypothesis is being examined using beta-cell-specific insulin and/or IGF-1 receptor knockouts and leptin receptor (ObRb) knockout mice and studying pathways that link leptin/insulin signaling with individual pathways that utilize PPARgamma, PGC1alpha and TRB3 in islets.

 

References:

 

BBS webpage updated 12/02/2009