Photo of Rohit Kulkarni,  MD, PhD

Rohit Kulkarni, MD, PhD

Harvard Medical School

Harvard Medical School
Phone: (617) 309-3460
Fax: (617) 306-3476


rohit.kulkarni@joslin.harvard.edu

Rohit Kulkarni, MD, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • Associate Professor, Medicine, Harvard Medical School
  • Senior Investigator, Section of Islet Cell & Regenerative Medicine , Joslin Diabetes Center

DF/HCC PROGRAM AFFILIATION

Research Abstract

The focus of the Kulkarni lab relates to understanding the signaling patwhays that promote growth and proliferation of islet cells. The lab has an interest in molecules that link growth factor signaling with proteins and pathways that also modulate tumor and uncontrolled proliferation. For example, p53 is a transcription factor which is the most frequently altered gene in human cancer. Mice deficient for p53 are developmentally normal but suceptible to spontaneous tumours. p53 is a cellular stress sensor leading to cell-cycle arrest, DNA repair, cellular senescence and apoptosis. We study the coordination and communication between the Insulin/IGF-1 and p53 signaling pathways in pancreatic islet growth. We are also intersted in the relevance of leptin signaling in the regulation of patheays that promote enhanced proliferation of progenitors in the adipocyte and endocrine lineages. We are undertaking studies to examine how mutations in the leptin receptor can modluate the ability of induced pluripotent stem cells to prolferate and differentiate towards different cell types.

Publications

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  • Valdez IA, Teo AK, Kulkarni RN. Cellular stress drives pancreatic plasticity. Sci Transl Med 2015; 7:273ps2. PubMed
  • Teo AK, Wagers AJ, Kulkarni RN. New opportunities: harnessing induced pluripotency for discovery in diabetes and metabolism. Cell Metab 2013; 18:775-91. PubMed
  • Su D, Shukla AK, Chen B, Kim JS, Nakayasu E, Qu Y, Aryal U, Weitz K, Clauss TR, Monroe ME, Camp DG, Bigelow DJ, Smith RD, Kulkarni RN, Qian WJ. Quantitative site-specific reactivity profiling of S-nitrosylation in mouse skeletal muscle using cysteinyl peptide enrichment coupled with mass spectrometry. Free Radic Biol Med 2013; 57:68-78. PubMed
  • Cheng K, Ho K, Stokes R, Scott C, Lau SM, Hawthorne WJ, O'Connell PJ, Loudovaris T, Kay TW, Kulkarni RN, Okada T, Wang XL, Yim SH, Shah Y, Grey ST, Biankin AV, Kench JG, Laybutt DR, Gonzalez FJ, Kahn CR, Gunton JE. Hypoxia-inducible factor-1alpha regulates beta cell function in mouse and human islets. J Clin Invest 2010; 120:2171-83. PubMed
  • Zhang Z, Liew CW, Handy DE, Zhang Y, Leopold JA, Hu J, Guo L, Kulkarni RN, Loscalzo J, Stanton RC. High glucose inhibits glucose-6-phosphate dehydrogenase, leading to increased oxidative stress and {beta}-cell apoptosis. FASEB J 2010; 24:1497-505. PubMed
  • Cornu M, Modi H, Kawamori D, Kulkarni RN, Joffraud M, Thorens B. Glucagon-like peptide-1 (GLP-1) increases beta-cell glucose competence and proliferation by translational induction of insulin-like growth factor-1 receptor (IGF-1R) expression. J Biol Chem 2010; 285:10538-45. PubMed
  • Kawamori D, Welters HJ, Kulkarni RN. Molecular Pathways Underlying the Pathogenesis of Pancreatic alpha-Cell Dysfunction. Adv Exp Med Biol 2010; 654:421-45. PubMed
  • Zhou JY, Petritis BO, Petritis K, Norbeck AD, Weitz KK, Moore RJ, Camp DG, Kulkarni RN, Smith RD, Qian WJ. Mouse-specific tandem IgY7-SuperMix immunoaffinity separations for improved LC-MS/MS coverage of the plasma proteome. J Proteome Res 2009; 8:5387-95. PubMed
  • Heinrichs S, Kulkarni RV, Bueso-Ramos CE, Levine RL, Loh ML, Li C, Neuberg D, Kornblau SM, Issa JP, Gilliland DG, Garcia-Manero G, Kantarjian HM, Estey EH, Look AT. Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics. Leukemia 2009; 23:1605-13. PubMed
  • Assmann A,Ueki K,Winnay JN,Kadowaki T,Kulkarni RN. Glucose effects on beta-cell growth and survival require activation of insulin receptors and insulin receptor substrate 2. Mol Cell Biol 2009; 29:3219-28. PubMed
  • Liu S, Okada T, Assmann A, Soto J, Liew CW, Bugger H, Shirihai OS, Abel ED, Kulkarni RN. Insulin signaling regulates mitochondrial function in pancreatic beta-cells. PLoS ONE 2009; 4:e7983. PubMed
  • Welters HJ,Kulkarni RN. Wnt signaling: relevance to beta-cell biology and diabetes. Trends Endocrinol Metab 2008; 19:349-55. PubMed
  • DeAngelis AM,Heinrich G,Dai T,Bowman TA,Patel PR,Lee SJ,Hong EG,Jung DY,Assmann A,Kulkarni RN,Kim JK,Najjar SM. Carcinoembryonic antigen-related cell adhesion molecule 1: a link between insulin and lipid metabolism. Diabetes 2008; 57:2296-303. PubMed
  • Tseng YH,Kokkotou E,Schulz TJ,Huang TL,Winnay JN,Taniguchi CM,Tran TT,Suzuki R,Espinoza DO,Yamamoto Y,Ahrens MJ,Dudley AT,Norris AW,Kulkarni RN,Kahn CR. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 2008; 454:1000-4. PubMed
  • Petyuk VA,Qian WJ,Hinault C,Gritsenko MA,Singhal M,Monroe ME,Camp DG 2nd,Kulkarni RN,Smith RD. Characterization of the mouse pancreatic islet proteome and comparative analysis with other mouse tissues. J Proteome Res 2008; 7:3114-26. PubMed
  • Handschin C, Choi CS, Chin S, Kim S, Kawamori D, Kurpad AJ, Neubauer N, Hu J, Mootha VK, Kim YB, Kulkarni RN, Shulman GI, Spiegelman BM. Abnormal glucose homeostasis in skeletal muscle-specific PGC-1alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalk. J Clin Invest 2007; 117:3463-74. PubMed
  • Morioka T, Asilmaz E, Hu J, Dishinger JF, Kurpad AJ, Elias CF, Li H, Elmquist JK, Kennedy RT, Kulkarni RN. Disruption of leptin receptor expression in the pancreas directly affects beta cell growth and function in mice. J Clin Invest 2007; 117:2860-8. PubMed
  • Matsumura K, Chang BH, Fujimya M, Chen W, Kulkarni RN, Eguchi Y, Kimura H, Kojima H, Chan L. Aquaporin 7 is a {beta} Cell Protein and Regulator of Intra-islet Glycerol Content and Glycerol Kinase Activity, {beta} Cell Mass, and Insulin Production and Secretion. Mol Cell Biol 2007; 27:6026-37. PubMed
  • Okada T, Liew CW, Hu J, Hinault C, Michael MD, Krtzfeldt J, Yin C, Holzenberger M, Stoffel M, Kulkarni RN. Insulin receptors in beta-cells are critical for islet compensatory growth response to insulin resistance. Proc Natl Acad Sci U S A 2007; 104:8977-82. PubMed
  • Kulkarni RN, Kahn CR. Ephs and ephrins keep pancreatic Beta cells connected. Cell 2007; 129:241-3. PubMed
  • Pissios P, Ozcan U, Kokkotou E, Okada T, Liew CW, Liu S, Peters JN, Dahlgren G, Karamchandani J, Kudva YC, Kurpad AJ, Kennedy RT, Maratos-Flier E, Kulkarni RN. Melanin concentrating hormone is a novel regulator of islet function and growth. Diabetes 2007; 56:311-9. PubMed
  • Koh HJ, Arnolds DE, Fujii N, Tran TT, Rogers MJ, Jessen N, Li Y, Liew CW, Ho RC, Hirshman MF, Kulkarni RN, Kahn CR, Goodyear LJ. Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves glucose homeostasis, and decreases TRB3. Mol Cell Biol 2006; 26:8217-27. PubMed
  • Qi L, Heredia JE, Altarejos JY, Screaton R, Goebel N, Niessen S, Macleod IX, Liew CW, Kulkarni RN, Bain J, Newgard C, Nelson M, Evans RM, Yates J, Montminy M. TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism. Science 2006; 312:1763-6. PubMed
  • Ueki K, Okada T, Hu J, Liew CW, Assmann A, Dahlgren GM, Peters JL, Shackman JG, Zhang M, Artner I, Satin LS, Stein R, Holzenberger M, Kennedy RT, Kahn CR, Kulkarni RN. Total insulin and IGF-I resistance in pancreatic beta cells causes overt diabetes. Nat Genet 2006; 38:583-8. PubMed
  • He Z, Opland DM, Way KJ, Ueki K, Bodyak N, Kang PM, Izumo S, Kulkarni RN, Wang B, Liao R, Kahn CR, King GL. Regulation of vascular endothelial growth factor expression and vascularization in the myocardium by insulin receptor and PI3K/Akt pathways in insulin resistance and ischemia. Arterioscler Thromb Vasc Biol 2006; 26:787-93. PubMed
  • Neubauer N, Kulkarni RN. Molecular approaches to study control of glucose homeostasis. ILAR J 2006; 47:199-211. PubMed
  • Gunton JE, Kulkarni RN, Yim S, Okada T, Hawthorne WJ, Tseng YH, Roberson RS, Ricordi C, O'Connell PJ, Gonzalez FJ, Kahn CR. Loss of ARNT/HIF1beta mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes. Cell 2005; 122:337-49. PubMed
  • Hennige AM, Ozcan U, Okada T, Jhala US, Schubert M, White MF, Kulkarni RN. Alterations in growth and apoptosis of insulin receptor substrate-1-deficient beta-cells. Am J Physiol Endocrinol Metab 2005; 289:E337-46. PubMed
  • Kulkarni RN. New insights into the roles of insulin/IGF-I in the development and maintenance of beta-cell mass. Rev Endocr Metab Disord 2005; 6:199-210. PubMed
  • Bates SH, Kulkarni RN, Seifert M, Myers MG. Roles for leptin receptor/STAT3-dependent and -independent signals in the regulation of glucose homeostasis. Cell Metab 2005; 1:169-78. PubMed
  • Kulkarni RN, Jhala US, Winnay JN, Krajewski S, Montminy M, Kahn CR. PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance. J Clin Invest 2004; 114:828-36. PubMed
  • Kulkarni RN, Roper MG, Dahlgren G, Shih DQ, Kauri LM, Peters JL, Stoffel M, Kennedy RT. Islet secretory defect in insulin receptor substrate 1 null mice is linked with reduced calcium signaling and expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)-2b and -3. Diabetes 2004; 53:1517-25. PubMed
  • Kulkarni RN. The islet beta-cell. Int J Biochem Cell Biol 2003; 36:365-71. PubMed
  • Kulkarni RN, Kahn CR. Molecular biology. HNFs--linking the liver and pancreatic islets in diabetes. Science 2004; 303:1311-2. PubMed
  • Du K, Herzig S, Kulkarni RN, Montminy M. TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver. Science 2003; 300:1574-7. PubMed
  • Kulkarni RN, Almind K, Goren HJ, Winnay JN, Ueki K, Okada T, Kahn CR. Impact of genetic background on development of hyperinsulinemia and diabetes in insulin receptor/insulin receptor substrate-1 double heterozygous mice. Diabetes 2003; 52:1528-34. PubMed
  • Kulkarni RN, Okada T. Tissue-specific targeting of the insulin receptor gene. Endocrine 2003; 19:257-66. PubMed
  • Kulkarni RN, Holzenberger M, Shih DQ, Ozcan U, Stoffel M, Magnuson MA, Kahn CR. beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass. Nat Genet 2002; 31:111-5. PubMed
  • Kulkarni RN, Winnay JN, Daniels M, Br. Altered function of insulin receptor substrate-1-deficient mouse islets and cultured beta-cell lines. J Clin Invest 1999; 104:R69-75. PubMed
  • Kulkarni RN, Br. Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 1999; 96:329-39. PubMed
  • Kulkarni RN, Wang ZL, Wang RM, Hurley JD, Smith DM, Ghatei MA, Withers DJ, Gardiner JV, Bailey CJ, Bloom SR. Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets and, in vivo, in mice. J Clin Invest 1998; 100:2729-36. PubMed
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