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: 6 postdoctoral fellows, 1 instructor, 2 graduate students, 1 lab manager, 2 research assistants


My lab is largely focused on exploring the growth factor (e.g. insulin and IGF) 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 continue to 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. For example, we have used Cre-LoxP and Flp-Frt techniques to create beta- or alpha-cell-specific knockout of multiple proteins to complement in vitro models using primary islets from humans and rodents and derived beta and alpha cell lines from the knockouts. Using these powerful and unique reagents we are investigating cross-talk between insulin, IGF-I, glucose and incretin (glucagon like-peptide-1) signaling mechanisms in islet cells. A major effort is directed towards evaluating specificity of insulin versus IGF signaling and their substrates in islet cell biology during embryonic and adult life. We are studying pathways utilized by lymphocytes that allow regeneration of beta cells in type 1 diabetes using NOD mice. To investigate the high incidence of type 2 diabetes in obese individuals we propose a potential link between adipocyte-derived factors (e.g. leptin) and growth factor signaling pathways at the level of the islet, to underlie islet function and growth. This hypothesis is being examined using islet-cell-specific knockouts of insulin and/or IGF-1 receptors and their substrates and the leptin receptor (ObRb) in mice. These studies will advance the field on several fronts - first, it will allow us to gain greater insights into the fundamental physiological mechanisms that govern the normal growth and functioning of 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 beta cell death and to plan alternative approaches to generate new beta cells to prevent and/or cure type 1 and type 2 diabetes.


While there continues to be debate regarding the origin of human and rodent islet cells, a major focus in our laboratory 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 (e.g. insulin, glucagon secreting 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, 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, screening drugs in vitro and the possibility of transplantation.


We are using transplantation and parabiotic approaches and techniques that allow us to investigate inter-organ communication and the identification of circulating islet cell growth factors (e.g. between islets and liver or brain 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 type 1 and type 2 diabetes.

Last Update: 7/21/2014


For a complete listing of publications click here.



ElOuaamari A, Kawamori, D, Dirice E, Liew CW, Shadrach JL, Hu J, Katsuta H, Hollister-Lock J, Qian W-J, Wagers AJ, Kulkarni RN. Liver-derived factors drive beta cell hyperplasia in insulin resistant states. Cell Reports 3(2):401-410, 2013 10.1016/j.celrep.2013.01.007 PMID:23375376

Liew CW, Boucher J, Cheong JK, Vernochet C, Mallol C, Townsend K, Langin D, Kawamori D, Hu J, Tseng Y-H, Hellerstein MK, Farmer SR, Goodyear L, Doria A, Bluher M, Hsu SI-H,
Kulkarni RN*. Ablation of TRIP-Br2, a novel regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance. Nature Medicine 19(2):217-226, 2013

Liew CW, Assmann A, Templin AT, Raum JC, Lipson KL, Rajan S, Hu J, Kawamori D, Lindberg I, Philipson L, Sonenberg N, Goldfine AB, Stoffers DA, Mirmira RG, Urano F,
Kulkarni RN. Insulin regulates carboxypeptidase E by modulating translation initiation scaffolding protein eIF4G1 in pancreatic beta cells. Proc Natl Acad Sci USA May 19, 2014. PMID:24843127

Mezza T, Muscogiuri G, Sorice GP, Clemente G, Hu J, Pontecorvi A, Holst JJ, Giaccari A,
Kulkarni RN. Insulin resistance alters islet morphology in non-diabetic humans. Diabetes 63:994-1007, 2014.

Dirice E, Kahraman S, Jiang W, ElOuaamari A, De Jesus DF, Teo AKK, Hu J, Kawamori D, Gaglia JL, Mathis D,
Kulkarni RN. Soluble factors secreted by T-cells promote beta cell proliferation. Diabetes 63(1):188-202, 2014. Epub 2013, Oct 2. PMID:24089508

Teo AK, Valdez I, Dirice E,
Kulkarni RN. Comparable generation of Activin-induced definitive endoderm via additive Wnt or BMP signaling in absence of serum. Stem Cell Reports 3:5-14, 2014

© 2015 by the President and Fellows of Harvard College