Hao Zhu, Ph.D.
Department of Clinical Laboratory Sciences
Ph.D., The University of Texas, 1994
Postdoctoral, Brigham and Women's Hospital, Harvard Medical School, 1995-1999
As a biochemist and molecular biologist, I have a long-standing research interest in the structure and function of biologically important proteins and their roles in human diseases. My focus in the past twelve years has been on Ncb5or (NADH cytochrome b5 oxidoreductase). This is a novel redox enzyme associated with pathogenesis of lean diabetes. The human Ncb5or gene is linked to lean diabetes, and the Ncb5or knockout mice develop early onset lean diabetes by age 7 weeks due to beta-cell dysfunction and death. Our recent findings show that Ncb5or deficiency in beta-cells leads to profound changes in lipid and iron metabolism, increased oxidative and ER stress, and lipotoxicity similar to that observed in animals with systemic lipid overload. Thus, our Ncb5or-null mouse represents a novel monogenic diabetes model. My lab is currently studying the role of Ncb5or in iron homeostasis and mitochondrial function and their relation to lipid metabolism in beta-cells and other cell types.
Zhu H, Qiu H, Yoon HP, Huang S, and Bunn HF. (1999) Identification of a Cytochrome b-type NAD(P)H Oxidoreductase Ubiquitously Expressed in Human Cells, Proc. Nat'l. Acad. Sci. (U.S.A.), 96:14742-14747.
Zhu H and Bunn HF. (2001) How Do Cells Sense Oxygen?, Science, 292:449-451.
Zhu H, Larade K, Jackson TA, Xie J, Ladoux A, Acker H, Berchner-Pfannschmidt U, Fandrey J, Cross AR, Lukat-Rodgers GS, Rodgers KR, and Bunn HF. (2004) NCB5OR is a novel soluble NAD(P)H reductase localized in the endoplasmic reticulum, J. Biol. Chem. (U.S.A.), 279:30316-30325.
Xie J, Zhu H, Larade K, Ladoux A, Seguritan A, Chu M, Ito S, Bronson RT, Leiter EH, Zhang CY, Rosen ED, and Bunn HF. (2004)Absence of a reductase, NCB5OR, causes insulin-deficient diabetes, Proc. Nat'l. Acad. Sci. (U.S.A.), 101: 10750-10755.
Larade K, Jiang ZG, Zhang YZ, Wang WF, Bonner-Weir S, Zhu H,* and Bunn HF*. (2008) Loss of Ncb5or results in impaired fatty acid desaturation, lipoatrophy and diabetes, J. Biol. Chem. (U.S.A.), 283:29285-29291. * Co-senior author
Zhang YZ, Larade K, Jiang ZG, Ito S, Wang WF, Zhu H,* and Bunn HF*. (2010) The flavoheme reductase Ncb5or protects cells against endoplasmic reticulum stress-induced lipotoxicity, J. Lipid Research. 51:53-62. *Co-senior author
Deng B, Parthasarathy S, Wang WF, Gibney BR, Battaile KP, Lovell SW, Benson DR*, and Zhu H*. (2010) Study of the individual cytochrome b5 and cytochrome b5 reductase domains of Ncb5or reveals a unique heme pocket and a possible role of the CS domain, J. Biol. Chem. (U.S.A.), 285:30181-30191. * Co-senior author
Xu M, Wang WF, Frontera JR, Neely MC, Lu J, Aires D, Hsu F, Turk J, Swerdlow HR, Carlson SE, and Zhu H. (2011) Ncb5or deficiency increases fatty acid catabolism and oxidative stress, J. Biol. Chem. (U.S.A.) 286:11141-11154.
Wang WF, Guo Y, Xu M, Huang H, Novikova L, Larade K, Jiang ZG, Thayer TC, Frontera JR, Aires D, Ding H, Turk J, Mathews CE, Bunn HF, Stehno-Bittel L, and Zhu H. (2011) Development of diabetes in lean Ncb5or-null mice is associated with manifestations of endoplasmic reticulum and oxidative stress in beta cells, Biochim Biophys Acta- Molecular Basis of Diseases, 1812:1532-41.
Guo Y, Xu M, Deng B, Frontera JR, Kover KL, Ding HL, Aires D, Carlson SE, Turk J, Wang WF*, and Zhu H*. (2012) Beta-cell injury in Ncb5or-null mice is exacerbated by consumption of a high-fat diet, European Journal of Lipid Science and Technology, 114:233-243.