Rohit N Kulkarni

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. Valdez I, Teo A, Kulkarni R. Cellular stress drives pancreatic plasticity. Sci Transl Med. 2015;7:273ps2 pubmed publisher
    ..Here, we highlight key findings in this provocative field and provide a perspective on possible exploitation of human pancreatic plasticity for therapeutic beta cell regeneration. ..
  2. Kulkarni R, Stewart A. Summary of the Keystone islet workshop (April 2014): the increasing demand for human islet availability in diabetes research. Diabetes. 2014;63:3979-81 pubmed publisher
  3. Liew C, Assmann A, Templin A, Raum J, Lipson K, Rajan S, et al. Insulin regulates carboxypeptidase E by modulating translation initiation scaffolding protein eIF4G1 in pancreatic ? cells. Proc Natl Acad Sci U S A. 2014;111:E2319-28 pubmed publisher
  4. Kulkarni R, Mizrachi E, Ocana A, Stewart A. Human β-cell proliferation and intracellular signaling: driving in the dark without a road map. Diabetes. 2012;61:2205-13 pubmed publisher
  5. El Ouaamari A, O Sullivan I, Shirakawa J, Basile G, Zhang W, Roger S, et al. Forkhead box protein O1 (FoxO1) regulates hepatic serine protease inhibitor B1 (serpinB1) expression in a non-cell-autonomous fashion. J Biol Chem. 2019;294:1059-1069 pubmed publisher
    ..These results indicate that liver FoxO1 promotes serpinB1 expression in hepatic insulin resistance and that non-cell-autonomous factors contribute to FoxO1-dependent effects on serpinB1 expression in the liver. ..
  6. Gupta M, De Jesus D, Kahraman S, Valdez I, Shamsi F, Yi L, et al. Insulin receptor-mediated signaling regulates pluripotency markers and lineage differentiation. Mol Metab. 2018;18:153-163 pubmed publisher
  7. De Jesus D, Kulkarni R. Epigenetic modifiers of islet function and mass. Trends Endocrinol Metab. 2014;25:628-36 pubmed publisher
    ..Unraveling the signaling pathways that regulate the islet epigenome during aging will help to better understand the development of disease progression and to design novel therapies for diabetes prevention. ..
  8. Gupta M, Teo A, Rao T, Bhatt S, Kleinridders A, Shirakawa J, et al. Excessive Cellular Proliferation Negatively Impacts Reprogramming Efficiency of Human Fibroblasts. Stem Cells Transl Med. 2015;4:1101-8 pubmed publisher
    ..These findings have implications for efficient reprogramming of human cells. ..
  9. Bhatt S, Gupta M, Khamaisi M, Martinez R, Gritsenko M, Wagner B, et al. Preserved DNA Damage Checkpoint Pathway Protects against Complications in Long-Standing Type 1 Diabetes. Cell Metab. 2015;22:239-52 pubmed publisher
    ..We propose miR200-regulated DNA damage checkpoint pathway as a potential therapeutic target for treating complications of diabetes. ..

More Information

Publications24

  1. Shirakawa J, Kulkarni R. Novel factors modulating human ?-cell proliferation. Diabetes Obes Metab. 2016;18 Suppl 1:71-7 pubmed publisher
    ..These studies provide important examples of proteins and pathways that may prove useful for designing therapeutic strategies to counter the different forms of human diabetes. ..
  2. Teo A, Lau H, Valdez I, Dirice E, Tjora E, Raeder H, et al. Early Developmental Perturbations in a Human Stem Cell Model of MODY5/HNF1B Pancreatic Hypoplasia. Stem Cell Reports. 2016;6:357-67 pubmed publisher
    ..Thus, patients typically develop MODY5 but not neonatal diabetes despite exhibiting pancreatic hypoplasia. ..
  3. Kawamori D, Shirakawa J, Liew C, Hu J, Morioka T, Duttaroy A, et al. GLP-1 signalling compensates for impaired insulin signalling in regulating beta cell proliferation in ?IRKO mice. Diabetologia. 2017;60:1442-1453 pubmed publisher
    ..Together, these data indicate the potential of GLP-1-related therapies to enhance beta cell proliferation and promote beneficial outcomes in models with dysfunctional beta cells. ..
  4. Patti M, Goldfine A, Hu J, Hoem D, Molven A, Goldsmith J, et al. Heterogeneity of proliferative markers in pancreatic β-cells of patients with severe hypoglycemia following Roux-en-Y gastric bypass. Acta Diabetol. 2017;54:737-747 pubmed publisher
    ..Markers of proliferation are heterogeneous in patients with severe post-RYGB hypoglycemia. Increased β-cell proliferation in some individuals may contribute to increased β-cell mass observed in severely affected patients. ..
  5. Mezza T, Shirakawa J, Martinez R, Hu J, Giaccari A, Kulkarni R. Nuclear Export of FoxO1 Is Associated with ERK Signaling in ?-Cells Lacking Insulin Receptors. J Biol Chem. 2016;291:21485-21495 pubmed
  6. Valdez I, Dirice E, Gupta M, Shirakawa J, Teo A, Kulkarni R. Proinflammatory Cytokines Induce Endocrine Differentiation in Pancreatic Ductal Cells via STAT3-Dependent NGN3 Activation. Cell Rep. 2016;15:460-470 pubmed publisher
    ..Together, our findings provide evidence that inflammatory cytokines direct ductal-to-endocrine cell differentiation, with implications for beta cell regeneration. ..
  7. El Ouaamari A, Dirice E, Gedeon N, Hu J, Zhou J, Shirakawa J, et al. SerpinB1 Promotes Pancreatic β Cell Proliferation. Cell Metab. 2016;23:194-205 pubmed publisher
    ..Together, these data implicate serpinB1 as an endogenous protein that can potentially be harnessed to enhance functional β cell mass in patients with diabetes. ..
  8. request reprint
    Kulkarni R, Kahn C. Ephs and ephrins keep pancreatic Beta cells connected. Cell. 2007;129:241-3 pubmed
    ..2007) show that the signaling proteins EphA and ephrin-A modulate insulin secretion, providing fresh insights into the functional significance of the clustering of beta cells, which occurs in islets. ..
  9. Shirakawa J, Kulkarni R. ERRγ-A New Player in β Cell Maturation. Cell Metab. 2016;23:765-7 pubmed publisher
    ..In a recent issue of Cell Metabolism, Yoshihara et al. (2016) report that estrogen-related receptor γ (ERRγ) promotes functional maturation of both mouse neonatal β cells and human iPSC-derived β-like cells. ..
  10. request reprint
    Kulkarni R, Holzenberger M, Shih D, Ozcan U, Stoffel M, Magnuson M, et al. 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
    ..Thus, Igf1r is not crucial for islet beta-cell development, but participates in control of differentiated function. ..
  11. Shirakawa J, Fernandez M, Takatani T, El Ouaamari A, Jungtrakoon P, Okawa E, et al. Insulin Signaling Regulates the FoxM1/PLK1/CENP-A Pathway to Promote Adaptive Pancreatic β Cell Proliferation. Cell Metab. 2017;25:868-882.e5 pubmed publisher
    ..These data implicate the insulin-FoxM1/PLK1/CENP-A pathway-regulated mitotic cell-cycle progression as an essential component in the β cell adaptation to delay and/or prevent progression to diabetes. ..
  12. Kahraman S, Dirice E, De Jesus D, Hu J, Kulkarni R. Maternal insulin resistance and transient hyperglycemia impact the metabolic and endocrine phenotypes of offspring. Am J Physiol Endocrinol Metab. 2014;307:E906-18 pubmed publisher
    ..The relatively smaller β-cell mass/area and β-cell proliferation in these control offspring suggest cell-autonomous epigenetic mechanisms in the regulation of islet growth and development. ..
  13. Kahraman S, Okawa E, Kulkarni R. Is Transforming Stem Cells to Pancreatic Beta Cells Still the Holy Grail for Type 2 Diabetes?. Curr Diab Rep. 2016;16:70 pubmed publisher
    ..While stem cell-derived beta-like cells provide an unlimited cell source for beta cell replacement therapies, these cells can also be used as a platform for drug screening or modeling diseases. ..
  14. Dirice E, Ng R, Martinez R, Hu J, Wagner F, Holson E, et al. Isoform-selective inhibitor of histone deacetylase 3 (HDAC3) limits pancreatic islet infiltration and protects female nonobese diabetic mice from diabetes. J Biol Chem. 2017;292:17598-17608 pubmed publisher
  15. request reprint
    Kulkarni R, Roper M, Dahlgren G, Shih D, Kauri L, Peters J, et al. 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