Research

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Umut  Ozcan, MD

Umut Ozcan, MD
Department:
Medicine Research
Division
Endocrinology Research
Hospital Title:
Medical Staff
Academic Title:
Associate Professor of Pediatrics, Harvard Medical School
Research Focus Area:
The molecular biology of ER stress and its relation to insulin and leptin resistance.

Research Overview

The primary aim of Ozcan laboratory is to delineate the molecular mechanisms of endoplasmic reticulum (ER) stress originated pathologies in obesity. The two main focus areas are insulin and leptin receptor signaling and their crosstalk with the unfolded protein response pathway. Dr. Ozcan's group employ a multi-disciplinary approach that draws on mouse genetics, endoplasmic reticulum physiology & pathophysiology, biochemistry, chemical biology and proteomics to identify key metabolic pathways that determine the cell’s response to physiologic and pathophysiologic ER stress. The ultimate goal of this integrated approach is to unravel the potential therapeutic targets in unfolded signaling pathway in order to reduce ER stress in obesity and find a cure for treatment of obesity and obesity-related diseases. The Ozcan group has made seminal discoveries in these areas and currently also working on potent drugs that could be future treatments for obesity and type 2 diabetes.

The Ozcan Laboratory Webpage: http://www.ozcanlab.com

About Umut Ozcan, MD

Umut Ozcan received his MD degree from the University of Istanbul. He completed his research training at the Joslin Diabetes Center and Harvard School of Public Health.

Publications

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  1. Lee J, Liu J, Feng X, Salazar Hernández MA, Mucka P, Ibi D, Choi JW, Ozcan U. Withaferin A is a leptin sensitizer with strong antidiabetic properties in mice. Nat Med. 2016 Sep; 22(9):1023-32.
  2. Herrema H, Zhou Y, Zhang D, Lee J, Salazar Hernandez MA, Shulman GI, Ozcan U. XBP1s Is an Anti-lipogenic Protein. J Biol Chem. 2016 Aug 12; 291(33):17394-404.
  3. Liu J, Lee J, Salazar Hernandez MA, Mazitschek R, Ozcan U. Treatment of obesity with celastrol. Cell. 2015 May 21; 161(5):999-1011.
  4. Park SW, Herrema H, Salazar M, Cakir I, Cabi S, Basibuyuk Sahin F, Chiu YH, Cantley LC, Ozcan U. BRD7 regulates XBP1s' activity and glucose homeostasis through its interaction with the regulatory subunits of PI3K. Cell Metab. 2014 Jul 1; 20(1):73-84.
  5. Cakir I, Ozcan U. Mom's milk molds neural wiring for metabolism. Cell. 2014 Jan 30; 156(3):396-7.
  6. Herrema H, Lee J, Zhou Y, Copps KD, White MF, Ozcan U. IRS1Ser³°7 phosphorylation does not mediate mTORC1-induced insulin resistance. Biochem Biophys Res Commun. 2014 Jan 10; 443(2):689-93.
  7. Lee J, Ozcan U. Unfolded protein response signaling and metabolic diseases. J Biol Chem. 2014 Jan 17; 289(3):1203-11.
  8. Ozcan U. Mitofusins: mighty regulators of metabolism. Cell. 2013 Sep 26; 155(1):17-8.
  9. Park SW, Ozcan U. Potential for therapeutic manipulation of the UPR in disease. Semin Immunopathol. 2013 May; 35(3):351-73.
  10. Sharara-Chami RI, Zhou Y, Ebert S, Pacak K, Ozcan U, Majzoub JA. Epinephrine deficiency results in intact glucose counter-regulation, severe hepatic steatosis and possible defective autophagy in fasting mice. Int J Biochem Cell Biol. 2012 Jun; 44(6):905-13.
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  12. Lee J, Sun C, Zhou Y, Lee J, Gokalp D, Herrema H, Park SW, Davis RJ, Ozcan U. p38 MAPK-mediated regulation of Xbp1s is crucial for glucose homeostasis. Nat Med. 2011 Oct; 17(10):1251-60.
  13. Zhou Y, Lee J, Reno CM, Sun C, Park SW, Chung J, Lee J, Fisher SJ, White MF, Biddinger SB, Ozcan U. Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction. Nat Med. 2011 Mar; 17(3):356-65.
  14. Park SW, Zhou Y, Lee J, Lee J, Ozcan U. Sarco(endo)plasmic reticulum Ca2+-ATPase 2b is a major regulator of endoplasmic reticulum stress and glucose homeostasis in obesity. Proc Natl Acad Sci U S A. 2010 Nov 9; 107(45):19320-5.
  15. Park SW, Zhou Y, Lee J, Lu A, Sun C, Chung J, Ueki K, Ozcan U. The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocation. Nat Med. 2010 Apr; 16(4):429-37.
  16. Ozcan L, Ergin AS, Lu A, Chung J, Sarkar S, Nie D, Myers MG, Ozcan U. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 2009 Jan 7; 9(1):35-51.
  17. Ozcan U, Ozcan L, Yilmaz E, Düvel K, Sahin M, Manning BD, Hotamisligil GS. Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Mol Cell. 2008 Mar 14; 29(5):541-51.
  18. 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 Feb; 56(2):311-9.
  19. Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith RO, Görgün CZ, Hotamisligil GS. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science. 2006 Aug 25; 313(5790):1137-40.
  20. 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 Aug; 289(2):E337-46.
  21. Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Görgün C, Glimcher LH, Hotamisligil GS. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004 Oct 15; 306(5695):457-61.
  22. Hennige AM, Burks DJ, Ozcan U, Kulkarni RN, Ye J, Park S, Schubert M, Fisher TL, Dow MA, Leshan R, Zakaria M, Mossa-Basha M, White MF. Upregulation of insulin receptor substrate-2 in pancreatic beta cells prevents diabetes. J Clin Invest. 2003 Nov; 112(10):1521-32.
  23. Rosen ED, Kulkarni RN, Sarraf P, Ozcan U, Okada T, Hsu CH, Eisenman D, Magnuson MA, Gonzalez FJ, Kahn CR, Spiegelman BM. Targeted elimination of peroxisome proliferator-activated receptor gamma in beta cells leads to abnormalities in islet mass without compromising glucose homeostasis. Mol Cell Biol. 2003 Oct; 23(20):7222-9.
  24. 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 May; 31(1):111-5.
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