BBS Faculty Member - Rohit Kulkarni

Rohit Kulkarni

Department of Cell Biology

Joslin Diabetes Center
Research, Room 410
One Joslin Place
Boston, MA 02215
Tel: 617-309-3460
Fax: 617-309-3476
Lab Members: 7 postdoctoral fellows, 2 instructors, 1 graduate student, 1 lab manager, 2 research assistants


The Kulkarni Lab has a major investment in investigating the significance of growth factor (e.g. insulin and insulin like growth factor-1) signaling pathways in the modulation of glucose sensing of beta cells, proinsulin processing, mitochondrial function, protection against apoptosis and ER stress and in regulating the expression of transcription factors in islet cells. We create genetic models to examine the roles of insulin and IGF-1 and -2 receptors and their substrates (insulin receptor substrates; IRS-1,2,3,4) and proteins downstream (e.g. Akt, FoxO1, PDX-1) in islet biology. We use Cre-LoxP and Flp-Frt techniques to create islet-cell-specific knockout (or knockin) of multiple proteins to complement in vitro models using primary islets from humans and rodents and derived beta and alpha cell lines from the genetically engineered models. Using these powerful and unique reagents we are investigating cross-talk between insulin, IGF-I, glucose, incretin (glucagon like-peptide-1) and leptin signaling pathways in islet cells. A major effort is directed towards evaluating specificity of insulin versus IGF signaling and their substrates and their actions in the nucleus in islet cells and hepatocytes during embryonic and adult life. We are studying pathways utilized by lymphocytes that allow regeneration of beta cells. To investigate the high incidence of type 2 diabetes in obesity we are exploring links between adipocyte-derived factors (e.g. leptin) and growth factor signaling pathways. This hypothesis is being examined using islet-cell-specific knockouts of insulin and/or IGF-1 receptors and their substrates and leptin receptor (ObRb) in mice. These studies will advance the field on several fronts - first, it will provide greater insights into the fundamental physiological mechanisms that govern the normal proliferation of the cell types and secretory function of the pancreatic islets; second, it will provide a physiological basis to identify targets in signaling pathways that would be useful to design potential therapeutic strategies to prevent islet cell death and to plan alternative approaches to generate new beta cells to prevent and/or cure human type 1 and type 2 diabetes.


A second area of focus in the Kulkarni Lab is to derive induced pluripotent stem (iPS) cells from skin fibroblasts and/or blood cells derived from living human donors (MODY and type 1 and type 2 diabetes patients) and rodent models with the long term goal of differentiating them into mature islet cells. There is also a focus on differentiating iPS cells into cells that are targets for complications observed in patients with type 1 and type 2 diabetes (e.g. vascular endothelial cells, neuronal cells, kidney cells, retinal pericytes). These approaches allow us to generate unique cells that maintain the genetic make-up of the living individual that would otherwise be unavailable, with the potential for characterizing their signaling properties, and for screening drugs to identity the most effective medications for individual patients.


We are using transplantation and parabiotic approaches and techniques that allow us to investigate inter-organ communication for the identification of circulating islet cell growth factors (e.g. between islets and liver or white/brown adipose). Identification of these putative factors will have the potential for harnessing them into therapeutics to enhance functional beta cell mass to counter human type 1 and type 2 diabetes.

Last Update: 12/7/2016


For a complete listing of publications click here.



Valdez IA, Dirice E, Gupta MK, Shirakawa J, Teo AKK, Kulkarni RN. Proinflammatory cytokines induce endocrine differentiation in pancreatic ductal cells via STAT3-dependent Ngn-3-activation. Cell Reports 15(3):460-470, 2016. PMID:27068459;PMCID:PMC4838491

Takatani T, Shirakawa J, Roe MW, Leech C, Maier B, Mirmira RA,
Kulkarni RN. IRS-1 deficiency protects β-cells against ER-stress-induced apoptosis by modulating sXBP-1 stability and protein translation. Sci Reports 6:28177, 2016 PMID:27378176; PMCID:PMC4932502

Mezza T, Shirakawa J, Martinez R, Hu J, Giaccari A,
Kulkarni RN. Nuclear export of FoxO1 is linked to ERK signaling in β-cells lacking insulin receptors. J Biol Chem 291:21485-21495, 2016 PMID:27535223; PMCID:PMC5076820

Molven A, Hollister-Lock J, Martinez R, Njolstad PR, Liew CW, Weir GC,
Kulkarni RN. The hypoglycemic phenotype is islet cell-autonomous on short-chain hydroxyl-CoA dehydrogenase (SCHAD) deficient mice. Diabetes 65(6):1672-1678, 2016. PMID:26953163
Teo AKK, Lau HH, Valdez I, Dirice E, Tjora E, Raeder H,
Kulkarni RN. Early developmental perturbations in a human stem cell model of MODY5/HNF1B pancreatic hypoplasia. Stem Cell Rep 6(3):357-367, 2016. PMID:26876668; PMCID:PMC4788763

El Ouaamari A, Dirice E, Gedeon N, Hu J, Zhou J-Y, Shirakawa J, Hou L, Goodman J, Karampelias C, Qiang G, Boucher J, Martinez R, Gritsenko MA, De Jesus DF, Kahraman S, Bhatt S, Smith RD, Beer H-D, Jungtrakoon, P, Gong Y, Goldfine AB, Liew CW, Doria A, Andersson O, Qian W-J, Remold-O’Donnell E,
Kulkarni RN. SerpinB1 promotes pancreatic β-cell proliferation. Cell Metabolism 23(1):194-205, 2016. PMID:26701651 PMCID:PMC4715773

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of Harvard College