Zhao Zhang, Ph.D.

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 June of 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.

• Diabetes
• Forward genetics
• Nonalcoholic fatty liver disease (NAFLD)
• Obesity
• Protein degradation

Featured Publications

Dynamic molecular architecture and substrate recruitment of cullin3-RING E3 ligase CRL3^KBTBD2.

Hu Y, Zhang Z, Mao Q, Zhang X, Hao A, Xun Y, Wang Y, Han L, Zhan W, Liu Q, Yin Y, Peng C, Moresco EMY, Chen Z, Beutler B, Sun L, Nat Struct Mol Biol 2024 Feb 31 2 336-350

Generation of epitope tag knock-in mice with CRISPR-Cas9 to study the function of endogenous proteins.

Zhang Z, STAR Protoc 2023 Aug 4 3 102518

OVOL2: an epithelial lineage determiner with emerging roles in energy homeostasis.

Jiang Y, Zhang Z, Trends Cell Biol 2023 Jun

Obesity caused by an OVOL2 mutation reveals dual roles of OVOL2 in promoting thermogenesis and limiting white adipogenesis.

Zhang Z, Jiang Y, Su L, Ludwig S, Zhang X, Tang M, Li X, Anderton P, Zhan X, Choi M, Russell J, Bu CH, Lyon S, Xu D, Hildebrand S, Scott L, Quan J, Simpson R, Sun Q, Qin B, Collie T, Tadesse M, Moresco EMY, Beutler B, Cell Metab 2022 Oct

Loss of immunity-related GTPase GM4951 leads to nonalcoholic fatty liver disease without obesity.

Zhang Z, Xun Y, Rong S, Yan L, SoRelle JA, Li X, Tang M, Keller K, Ludwig S, Moresco EMY, Beutler B, Nat Commun 2022 Jul 13 1 4136

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

• Keynote Session: Forward Genetics of Fatty Liver Disease, Gordon Research Conference
  (2022)
• The NIH Research Project Grant (R01) (NIDDK)
  (2022)
• NIH Pathway to Independence Award (K99/R00) (NIDDK)
  (2017)
• Keystone Symposia Future of Science Fund Scholarship
  (2016)
• President Scholarship of Chinese Academy of Sciences
  (2014)
• National Scholarship, Ministry of Education of China
  (2013)
• CSBMB-YSP Travel Fellowship of 13th FAOBMB Congress
  (2012)
• National Scholarship, Ministry of Education of China
  (2012)
• Travel Fellowship of 1st Asia-Pacific Drosophila Research Conference
  (2011)

• Ad hoc Member, NIH Nutrition and Metabolism in Health and Disease (NMHD) study section (2022)
• Member of American Diabetes Association (2023)
• Member of Chinese American Diabetes Association (2020)