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Related Research Units

Endocrinology Research
Ozcan Lab Research

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.

Research Background

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

  1. Central inhibition of HDAC6 re-sensitizes leptin signaling during obesity to induce profound weight loss. Cell Metab. 2024 Apr 02; 36(4):857-876.e10. View Abstract
  2. FKBP11 rewires UPR signaling to promote glucose homeostasis in type 2 diabetes and obesity. Cell Metab. 2022 07 05; 34(7):1004-1022.e8. View Abstract
  3. Antisense-mediated senseful regulation of orchestrated metabolic response. Cell Chem Biol. 2022 04 21; 29(4):539-540. View Abstract
  4. Transcription- and phosphorylation-dependent control of a functional interplay between XBP1s and PINK1 governs mitophagy and potentially impacts Parkinson disease pathophysiology. Autophagy. 2021 12; 17(12):4363-4385. View Abstract
  5. Yin Yang 1 protein ameliorates diabetic nephropathy pathology through transcriptional repression of TGFß1. Sci Transl Med. 2019 09 18; 11(510). View Abstract
  6. Lipocalin 2 Does Not Play A Role in Celastrol-Mediated Reduction in Food Intake and Body Weight. Sci Rep. 2019 09 05; 9(1):12809. View Abstract
  7. IL1R1 is required for celastrol's leptin-sensitization and antiobesity effects. Nat Med. 2019 04; 25(4):575-582. View Abstract
  8. PGC-1a functions as a co-suppressor of XBP1s to regulate glucose metabolism. Mol Metab. 2018 01; 7:119-131. View Abstract
  9. Selective Chemical Inhibition of PGC-1a Gluconeogenic Activity Ameliorates Type 2 Diabetes. Cell. 2017 03 23; 169(1):148-160.e15. View Abstract
  10. Inflammation Improves Glucose Homeostasis through IKKß-XBP1s Interaction. Cell. 2016 11 03; 167(4):1052-1066.e18. View Abstract
  11. Withaferin A is a leptin sensitizer with strong antidiabetic properties in mice. Nat Med. 2016 09; 22(9):1023-32. View Abstract
  12. XBP1s Is an Anti-lipogenic Protein. J Biol Chem. 2016 08 12; 291(33):17394-404. View Abstract
  13. Treatment of obesity with celastrol. Cell. 2015 May 21; 161(5):999-1011. View Abstract
  14. BRD7 regulates XBP1s' activity and glucose homeostasis through its interaction with the regulatory subunits of PI3K. Cell Metab. 2014 Jul 01; 20(1):73-84. View Abstract
  15. Mom's milk molds neural wiring for metabolism. Cell. 2014 Jan 30; 156(3):396-7. View Abstract
  16. IRS1Ser³°7 phosphorylation does not mediate mTORC1-induced insulin resistance. Biochem Biophys Res Commun. 2014 Jan 10; 443(2):689-93. View Abstract
  17. Unfolded protein response signaling and metabolic diseases. J Biol Chem. 2014 Jan 17; 289(3):1203-11. View Abstract
  18. Mitofusins: mighty regulators of metabolism. Cell. 2013 Sep 26; 155(1):17-8. View Abstract
  19. Potential for therapeutic manipulation of the UPR in disease. Semin Immunopathol. 2013 May; 35(3):351-73. View Abstract
  20. 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. View Abstract
  21. p38 MAPK-mediated regulation of Xbp1s is crucial for glucose homeostasis. Nat Med. 2011 Sep 04; 17(10):1251-60. View Abstract
  22. Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction. Nat Med. 2011 Mar; 17(3):356-65. View Abstract
  23. 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 09; 107(45):19320-5. View Abstract
  24. 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. View Abstract
  25. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 2009 Jan 07; 9(1):35-51. View Abstract
  26. 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. View Abstract
  27. Melanin concentrating hormone is a novel regulator of islet function and growth. Diabetes. 2007 Feb; 56(2):311-9. View Abstract
  28. 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. View Abstract
  29. Alterations in growth and apoptosis of insulin receptor substrate-1-deficient beta-cells. Am J Physiol Endocrinol Metab. 2005 Aug; 289(2):E337-46. View Abstract
  30. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004 Oct 15; 306(5695):457-61. View Abstract
  31. Upregulation of insulin receptor substrate-2 in pancreatic beta cells prevents diabetes. J Clin Invest. 2003 Nov; 112(10):1521-32. View Abstract
  32. 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. View Abstract
  33. 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. View Abstract

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