Dr. Zhao Zhang obtained his B.S. in Biotechnology from Shandong University in 2008. He received his Ph.D. in Developmental Biology from the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences in 2014 under the direction of Dr. Yun Zhao. Right after graduation, He joined the lab of Dr. Bruce Beutler at UT Southwestern Medical Center for his post-doctoral training.
Over the years from graduate research to postdoctoral research, Dr. Zhang has been working on the molecular mechanisms of human diseases with different model organisms. His graduate work focused on the study of the Hedgehog (Hh) signaling pathway in zebrafish and Drosophila. He identified several new regulators of the Hh signaling pathway and a new role for Hh signaling in the Drosophila testis stem cell niche. His postdoctoral work focused on the mouse forward genetics screens to identify new regulators of Toll-like receptor (TLR) signaling pathways, tumor metastasis, obesity, diabetes, and nonalcoholic fatty liver disease (NAFLD). Among all of these different screens, his most significant scientific contribution is the identification of a new metabolic syndrome termed teeny in mice with a mutation in a new gene Kbtbd2. His work revealed the critical role of KBTBD2 as an E3 ubiquitin ligase to precisely control the abundance of the regulatory subunit of the PI3K pathway, p85α. Based on this work, he secured an NIH Pathway to Independence Award (K99/R00) in 2017 to further explore the role of KBTBD2 in lipodystrophy, insulin resistance, and diabetes.
In 2020, Dr. Zhang began his independent research career as an Assistant Professor in the Center for the Genetics of Host Defense at UT Southwestern Medical Center. The long-term goal of the Zhang lab is to understand the key molecular mechanism to maintain the energy balance in our body, with the underlying aim of translating this knowledge into novel therapeutic strategies. The following specific directions are currently explored in the Zhang lab, including: 1) The dynamic regulation of KBTBD2 by post-translational modifications. 2) Novel BTB domain proteins in the regulation of obesity and diabetes. 3) The role of a new allele in thermogenesis and energy balance. 4) The mechanism of a new gene in the pathogenesis of NAFLD.
- Nonalcoholic fatty liver disease (NAFLD)
- Protein degradation
- Tissue-specific disruption of Kbtbd2 uncovers adipocyte-intrinsic and -extrinsic features of the teeny lipodystrophy syndrome.
- Zhang Z, Gallagher T, Scherer PE, Beutler B, Proc. Natl. Acad. Sci. U.S.A. 2020 May 117 21 11829-11835
- Insulin resistance and diabetes caused by genetic or diet-induced KBTBD2 deficiency in mice.
- Zhang Z, Turer E, Li X, Zhan X, Choi M, Tang M, Press A, Smith SR, Divoux A, Moresco EM, Beutler B Proc. Natl. Acad. Sci. U.S.A. 2016 Oct 113 42 E6418-E6426
- The Transitional Endoplasmic Reticulum ATPase p97 Regulates the Alternative Nuclear Factor NF-?B Signaling via Partial Degradation of the NF-?B Subunit p100.
- Zhang Z, Wang Y, Li C, Shi Z, Hao Q, Wang W, Song X, Zhao Y, Jiao S, Zhou Z J. Biol. Chem. 2015 Jun
- Atrophin-Rpd3 complex represses Hedgehog signaling by acting as a corepressor of CiR.
- Zhang Z, Feng J, Pan C, Lv X, Wu W, Zhou Z, Liu F, Zhang L, Zhao Y, J. Cell Biol. 2013 Nov 203 4 575-83
- Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover.
- Huang S, Zhang Z, Zhang C, Lv X, Zheng X, Chen Z, Sun L, Wang H, Zhu Y, Zhang J, Yang S, Lu Y, Sun Q, Tao Y, Liu F, Zhao Y, Chen D PLoS Biol. 2013 Nov 11 11 e1001721
- Hedgehog in the Drosophila testis niche: what does it do there?
- Zhang Z, Pan C, Zhao Y, Protein Cell 2013 Sep 4 9 650-5
- Ter94 ATPase complex targets k11-linked ubiquitinated ci to proteasomes for partial degradation.
- Zhang Z, Lv X, Yin WC, Zhang X, Feng J, Wu W, Hui CC, Zhang L, Zhao Y Dev. Cell 2013 Jun 25 6 636-44
- Dual roles of Hh signaling in the regulation of somatic stem cell self-renewal and germline stem cell maintenance in Drosophila testis.
- Zhang Z, Lv X, Jiang J, Zhang L, Zhao Y Cell Res. 2013 Feb
- Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development.
- Choi JH, Zhong X, Zhang Z, Su L, McAlpine W, Misawa T, Liao TC, Zhan X, Russell J, Ludwig S, Li X, Tang M, Anderton P, Moresco EMY, Beutler B, J. Exp. Med. 2020 Apr 217 4
- Enhanced susceptibility to chemically induced colitis caused by excessive endosomal TLR signaling in LRBA-deficient mice.
- Wang KW, Zhan X, McAlpine W, Zhang Z, Choi JH, Shi H, Misawa T, Yue T, Zhang D, Wang Y, Ludwig S, Russell J, Tang M, Li X, Murray AR, Moresco EMY, Turer EE, Beutler B, Proc. Natl. Acad. Sci. U.S.A. 2019 May
Honors & Awards
- NIH Pathway to Independence Award (K99/R00) (NIDDK)
- Keystone Symposia Future of Science Fund Scholarship
- President Scholarship of Chinese Academy of Sciences
- CSBMB-YSP Travel Fellowship of 13th FAOBMB Congress
- Travel Fellowship of 1st Asia-Pacific Drosophila Research Conference