Dr. Fawaz Haj

Dr. Fawaz Haj

Welcome to the website for the laboratory of Dr. Fawaz Haj in the Department of Nutrition at the University of California, Davis.

Dr. Haj’s laboratory studies the molecular basis of metabolic diseases with a focus on type 2 diabetes and its complications. The team investigates the role of key signaling molecules, namely protein tyrosine phosphatases and their interacting partners, in metabolic regulation. This is achieved through the combined use of cellular, biochemical, gene knockout and system biology approaches.


  • B.Sc., Biology, American University of Beirut
  • M.Sc., Biomedical Sciences, Bradford University
  • D.Phil., Physiology, Oxford University

Post Graduate Training

  • Postdoctoral Fellow, Harvard Medical School
  • Instructor in Medicine, Harvard Medical School
  • Visiting Scientist, European Molecular Biology Laboratory

Academic Appointments

  • Assistant Professor, Nutrition Department, University of California Davis, 2007-2011
  • Associate Professor, Nutrition Department, University of California Davis, 2011-2015
  • Associate Professor, Internal Medicine Department, University of California Davis, 2012-2015
  • Professor, Nutrition Department, University of California, 2015-present
  • Professor, Internal Medicine Department, University of California Davis, 2015-present

Administrative Appointments

  • Director, Meyer Hall Animal Facility, University of California Davis, 2008-present
  • Co-Director, Metabolism and Endocrinology Core, National Mouse Metabolic Phenotyping Center, University of California Davis, 2011-present

Awards and Honors

  • Oxford University, Oxford Overseas Bursaries, 1997
  • Oxford University, Overseas Research Scholarship, 1997
  • Harvard University, Certificate of Excellence in Research, 2001
  • American Diabetes Association Junior Faculty Award, 2006
  • University of California Davis, Hellman Fellow, 2008

Oral presentations


  • Division of Endocrinology, Diabetes and Metabolism, University of Miami, Miami, Florida, USA
  • School of Medicine, University of Miami, Miami, Florida, USA
  • Pre-Obesity Society Symposium, Orlando, Florida, USA
  • 9th International Conference on Protein Phosphatases, Tokyo, Japan
  • Department of Microbiology, Yokohama City University, Yokohama, Japan
  • EMBO conference on protein phosphatases, Vienna, Austria
  • Department of Biology, University of Copenhagen, Copenhagen, Denmark
  • Frontiers of Science, Engineering and Medicine Symposium, Kuwait Institute for Scientific Research, Kuwait City, Kuwait
  • Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
  • Taiwan Society for Biochemistry and Molecular Biology, Taipei, Taiwan
  • Department of Biological Sciences, National University of Singapore, Singapore
  • Duke-National University of Singapore Graduate Medical School, Singapore


  • Comprehensive Cancer Center, University of California Davis, Sacramento, CA, USA
  • Department of Orthopedics, University of California Davis, Sacramento, CA, USA
  • Protein Phosphatases Conference, Silvertree, CO, USA
  • Department of Nutritional Biology and Toxicology, University of California Berkeley, CA, USA
  • Phosphatases in human disease conference, Melbourne, Australia
  • Garvan Institute, Sydney, Australia
  • International conference on obesity and weight management, Philadelphia, PA, USA
  • Royal Society Metabolism and Endocrinology Themed Meeting, London, UK.


  • Division of Endocrinology, Diabetes and Metabolism, University of California Davis, Sacramento, CA
  • 10th International Conference on Protein Phosphatases and Diseases, Tokyo, Japan
  • Brain-Liver Interface Medicine Research Center, Kanazawa University, Kanazawa, Japan
  • Nutrition, Oxygen Biology and Medicine Conference, Paris, France
  • Department of Molecular Cell Biology, University of Leuven, Belgium
  • VI International Conference on Polyphenols and Health, Buenos Aires, Argentina
  • Institute of Biomedical Investigation Alberto Sols, Madrid, Spain
  • Department of Physiology, University of Valencia, Valencia, Spain
  • Biotechnology Research Institute, University of San Martin, Buenos Aires, Argentina


  • MRC Clinical Sciences Centre, Imperial College, London, UK
  • Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University, Oxford, UK
  • 17 th Biennial Meeting of Society for Free Radical Research International, Kyoto, Japan
  • Foods For Health Institute, University of California Davis, Davis, CA, USA
  • Comprehensive Cancer Center, University of California Davis, Sacramento, CA, USA
  • FASEB conference on Protein Phosphatases, Nassau, Bahamas
  • 11th International Conference on Protein Phosphatases, Sendai, Japan


Contributions to Science

Protein tyrosine phosphatases and their substrates as key metabolic regulators.

PTPs are important regulators of cell signaling and are essential for maintaining homeostasis. We investigate the metabolic functions of PTPs using tissue-specific deletion, biochemical and metabolomics approaches. These include protein-tyrosine phosphatase 1B (PTP1B), Src homology phosphatase 2 (Shp2) and T cell protein-tyrosine phosphatase (TCPTP). In a series of studies using biochemical and mass spectroscopy approaches we identify and validate new physiological substrates for PTP1B in adipose tissue including endoplasmic reticulum stress kinase PERK, rate-limiting glycolytic enzyme pyruvate kinase M2, and SNARE-interacting protein Munc18c. In additional studies we identify hepatic Shp2 as a regulator of systemic glucose homeostasis and as a novel regulator of energy balance under conditions of high fat feeding. Moreover, we demonstrate that pancreatic TCPTP deficiency mitigates acute pancreatitis and affects pancreatic beta cell function and insulin secretion. Together, these findings implicate PTPs and their interacting partners in the regulation of glucose homeostasis and energy balance in vivo.


  1.  Ahmed Bettaieb, Siming Liu, Yannan Xi, Naoto Nagata, Kosuke Matsuo, Izumi Matsuo, Samah Chahed, Jesse Bakke, Heike Keilhack, Tony Tiganis and Fawaz Haj (2011). Differential regulation of endoplasmic reticulum stress by protein tyrosine phosphatase 1B and T cell protein tyrosine phosphatase. Journal of Biological Chemistry, Mar 18;286(11):9225-35.  [PubMed]
  2. Naoto Nagata, Kosuke Matsuo, Ahmed Bettaieb, Jesse Bakke, Izumi Matsuo, James Graham, Yannan Xi, Siming Liu, Alexey Tomilov, Natalia Tomilova, Susan Gray, Dae Young Jung, Jon Ramsey, Jason Kim, Gino Cortopassi, Peter Havel and Fawaz Haj (2012). Hepatic Src Homology Phosphatase 2 regulates energy balance in mice. Endocrinology, Jul;153(7):3158-69. [PubMed]
  3. Bettaieb A, Bakke J, Nagata N, Matsuo K, Xi Y, Liu S, AbouBechara D, Melhem R, Stanhope K, Cummings B, Graham J, Bremer A, Zhang S, Lyssiotis CA, Zhang ZY, Cantley LC, Havel PJ, Haj FG. Protein tyrosine phosphatase 1B regulates pyruvate kinase M2 tyrosine phosphorylation. J Biol Chem. 2013 Jun 14;288(24):17360-71. [PubMed]
  4. Bettaieb, A., Xi, Y., Hosein, E., Coggins, N., Bachaalany, S., Wiede, F., Perez, P., Griffey, S., Sastre, J., Tiganis, T., and Haj, F* (2014). Pancreatic T cell Protein-tyrosine phosphatase deficiency ameliorates cerulein-induced acute pancreatitis. Cell Communication and Signaling, 12:13.
  5. Xi Y, Liu S, Bettaieb A, Matsuo K, Matsuo I, Hosein E, Chahed S, Wiede F, Zhang S, et al. Pancreatic T cell protein-tyrosine phosphatase deficiency affects beta cell function in mice. Diabetologia. 2015 Jan;58:122-31. [PubMed]
  6. Hsu MF, Pan KT, Chang FY, Khoo KH, Urlaub H, Cheng CF, Chang GD, Haj FG, Meng TC. S-nitrosylation of endogenous protein tyrosine phosphatases in endothelial insulin signaling. Free Radic Biol Med. 2016 Aug 10;99:199-213. [PubMed]


Spatial and temporal control of cellular signaling by protein tyrosine phosphatases.

Using biochemical and quantitative cellular imaging we investigate the spatial and temporal interaction of PTPs and their substrates. We report that endoplasmic reticulum-anchored PTP1B plays an important role in regulating receptor tyrosine kinase (RTK) signaling. Using Florescence Resonance Energy Transfer we demonstrate that most of the activated RTKs interact with PTP1B after internalization, establishing that RTK activation and inactivation are spatially and temporally partitioned within cells. In additional studies we establish that PTP1B plays a dynamic role in regulating signaling at regions of cell-cell contact and identify plasma membrane proximal sub-regions of the ER as important sites for regulating cellular signaling. Further, we uncovered a novel mechanism whereby PTP1B regulates pancreatic beta cell-cell communication through modifying Eph kinase phosphorylation. Together, these studies successfully address the spatio-temporal interactions of PTPs and their substrates and implications on cell signaling.

  1.  badgef1000Fawaz Haj, Peter Verveer, Anthony Squire, Benjamin Neel and Philippe Bastiaens (2002).  Imaging sites of receptor dephosphorylation by PTP1B on the surface of the endoplasmic reticulum.  Science.  Mar, 295 (5560): 1708-11. [PubMed]
    Fawaz Haj, Boyka Markova, Lori Klaman, Frank Bohmer and Benjamin Neel (2003).  Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatase-1B.  Journal of Biological Chemistry.  Jan 10, 278 (2): 739-44. [PubMed]
  2. Eva Nievergall, Peter Janes, Carolin Stegmayer, Mary Vail, Fawaz Haj, Shyh Wei Teng, Benajmin Neel, Philippe Bastiaens and Martin Lackman (2010). Protein-Tyrosine Phosphatase 1B regulates Eph receptor function and trafficking. Journal of Cell Biology, Dec 13; 191(6):1189-203. [PubMed]
  3. Fawaz Haj, Ola Sabet, Ali Kinkhabwala, Sabine Wimmer-Kleikamp, Vassilis Roukos,Hong-Mei Han, Markus Grabenbauer, Martin Bierbaum, Claude Antony, Benjamin Neel, and Philippe Bastiaens (2012). Regulation of signaling at regions of cell-cell contact by endoplasmic reticulum-bound protein-tyrosine phosphatase 1B. PLoS One, 7(5):e36633. [PubMed].
  4. Bakke J, Haj FG. Protein-tyrosine phosphatase 1B substrates and metabolic regulation. Seminars in cell & developmental biology. 2015 Jan;37C:58-65. [PubMed]



Soluble epoxide hydrolase as a therapeutic target for type 2 diabetes and its complications.

sEH deficiency and pharmacological inhibition have beneficial effects in cardiovascular and inflammatory diseases in murine models. We investigate the role of sEH in metabolic diseases and type 2 diabetes and its complications. In collaboration with the Hammock laboratory (UCD) we demonstrate that sEH deficiency and inhibition in mice improve insulin signaling and enhance glucose tolerance. In follow up studies we demonstrate that the salutary effects of sEH deficiency on glucose homeostasis are due, at least in part, to attenuation of endoplasmic reticulum (ER) stress in a cell autonomous manner. Notably, regulation of ER stress by sEH appears to be a common mechanism that underlies the salutary effects of sEH deficiency. Indeed, in a series of studies we establish that sEH deficiency and pharmacological inhibition rapidly reduce pain related behavior and diabetic neuropathy, and this is directly caused by attenuation of ER stress. Moreover, we report that sEH deficiency mitigates experimental acute pancreatitis (AP) in mice. Further, sEH pharmacological inhibition after induction of AP mitigates the severity of the disease suggesting that sEH inhibition may be of therapeutic value in acute pancreatitis. Together, these studies establish a role of sEH in metabolic regulation and uncover key signaling mechanisms that mediate sEH metabolic actions.


  1. Bettaieb A, Nagata N, AbouBechara D, Chahed S, Morisseau C, Hammock BD, Haj FG. Soluble epoxide hydrolase deficiency or inhibition attenuates diet-induced endoplasmic reticulum stress in liver and adipose tissue. J Biol Chem. 2013 May 17;288(20):14189-99. [PubMed]
  2. Ayala Luria, Ahmed Bettaieb, Yannan Xi, Guang-Jong Shieh, Hsin-Chen Liu, Hiromi Inoue, Hsing-Ju Tsai, John Imig, Fawaz Haj and Bruce Hammock (2011). Soluble epoxide hydrolase deficiency alters pancreatic islet size and improves glucose homeostasis in a model of insulin resistance induced by high fat diet. Proceedings of the National Academy of Sciences, May 31;108(22):9038-43. [PubMed]
  3. badgef1000Bora Inceoglu, Karen Wagner, Jun Yang, Ahmed Bettaieb, Nils Schebb, Fawaz Haj, Bruce Hammock (2012). Acute augmentation of epoxygenated fatty acid levels rapidly reduces pain-related behavior in a rat model of type I diabetes.Proceedings of the National Academy of Sciences, Jul 10;109(28):11390-5. [PubMed]
  4. Bettaieb A, Chahed S, Bachaalany S, Griffey S, Hammock BD, Haj FG. Soluble Epoxide Hydrolase Pharmacological Inhibition Ameliorates Experimental Acute Pancreatitis in Mice. Mol Pharmacol. 2015 Aug;88(2):281-90. (epub ahead of print) [PubMed]
  5. Inbadgef1000ceoglu B, Bettaieb A, Trindade da Silva CA, Lee KS, Haj FG, Hammock BD. Endoplasmic reticulum stress in the peripheral nervous system is a significant driver of neuropathic pain. Proceedings of the National Academy of Sciences, 112(29):9082-7. [PubMed]