Heart Institute

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Zhigao Wang

Zhigao Wang, PhD

Associate Professor, Medicine

Contact Info

Education

  • PhD, Genetics and Development, UT Southwestern Medical Center, 2004
  • BS, Biochemistry, Wuhan University, 1994

Academic Philosophy

"The long term goal of the Wang lab is to understand the molecular mechanisms of necrotic cell death pathways and to develop chemical compounds that will help treat necrosis-associated diseases, including cardiac injury, infections and inflammation."

Interdisciplinary and Emerging Signature Programs

  • Allergy, Immunology & Infectious Disease
  • Cancer Biology
  • Cardiovascular Sciences
  • Cellular and Molecular Biology

Research Interests

  • The long term goal of the Wang lab is to understand the molecular mechanisms of necrotic cell death pathways and to develop chemical compounds that will help treat necrosis-associated diseases, including cardiac injury, infections, inflammation, neurodegeneration and cancer. We currently have two major research foci in the lab. In our first, more established research program, we employ CRISPR-mediated whole genome knockout screens to identify novel players in the cell death pathways. The other focus is on the identification of new pathway inhibitors and activators derived from completed chemical library screens. Our approach has already resulted in the identification of new molecular regulators of the necroptosis pathway (Nature Communication 2021 and PNAS 2020a) and a novel necroptosis blocking compound (PNAS 2020b) as well as the repurposing of a compound previously unknown to be an activator of necroptosis (JBC, 2017).

Recent Publications

  • Du J, Xiang Y, Liu H, Liu S, Kumar A, Xing C, Wang Z. RIPK1 dephosphorylation and kinase activation by PPP1R3G/PP1γ promote apoptosis and necroptosis. Nature communications. 12(1) : 7067, 2021.
  • Yu B, Ma J, Li J, Wang D, Wang Z, Wang S. Mitochondrial phosphatase PGAM5 modulates cellular senescence by regulating mitochondrial dynamics. Nature communications. 11(1) : 2549, 2020.
  • Johnston AN, Ma Y, Liu H, Liu S, Hanna-Addams S, Chen S, Chen C, Wang Z. Necroptosis-blocking compound NBC1 targets heat shock protein 70 to inhibit MLKL polymerization and necroptosis. Proceedings of the National Academy of Sciences of the United States of America. 117(12) : 6521-6530, 2020.
  • Hanna-Addams S, Liu S, Liu H, Chen S, Wang Z. CK1α, CK1δ, and CK1ε are necrosome components which phosphorylate serine 227 of human RIPK3 to activate necroptosis. Proceedings of the National Academy of Sciences of the United States of America. 117(4) : 1962-1970, 2020.
  • Johnston AN, Wang Z. HSP70 promotes MLKL polymerization and necroptosis. Molecular & cellular oncology. 7(5) : 1791561, 2020.
  • Hanna-Addams S, Wang Z. Use of Two Dimensional Semi-denaturing Detergent Agarose Gel Electrophoresis to Confirm Size Heterogeneity of Amyloid or Amyloid-like Fibers. Journal of visualized experiments : JoVE. (134) , 2018.
  • Johnston A, Wang Z. Necroptosis: MLKL Polymerization. Journal of nature and science. 4(7) , 2018.
  • Li Y, Zhang Z, Chen J, Liu W, Lai W, Liu B, Li X, Liu L, Xu S, Dong Q, Wang M, Duan X, Tan J, Zheng Y, Zhang P, Fan G, Wong J, Xu GL, Wang Z, Wang H, Gao S, Zhu B. Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1. Nature. 564(7734) : 136-140, 2018.
  • Liu S, Liu H, Johnston A, Hanna-Addams S, Reynoso E, Xiang Y, Wang Z. MLKL forms disulfide bond-dependent amyloid-like polymers to induce necroptosis. Proceedings of the National Academy of Sciences of the United States of America. 114(36) : E7450-E7459, 2017.
  • Reynoso E, Liu H, Li L, Yuan AL, Chen S, Wang Z. Thioredoxin-1 actively maintains the pseudokinase MLKL in a reduced state to suppress disulfide bond-dependent MLKL polymer formation and necroptosis. The Journal of biological chemistry. 292(42) : 17514-17524, 2017.
  • Wang Z, Jiang H, Chen S, Du F, Wang X. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell. 148(1) : 228-43, 2012.
  • Sun L, Wang H, Wang Z, He S, Chen S, Liao D, Wang L, Yan J, Liu W, Lei X, Wang X. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 148(1) : 213-27, 2012.
  • Wang J, Li A, Wang Z, Feng X, Olson EN, Schwartz RJ. Myocardin sumoylation transactivates cardiogenic genes in pluripotent 10T1/2 fibroblasts. Molecular and cellular biology. 27(2) : 622-32, 2007.
  • Xing W, Zhang TC, Cao D, Wang Z, Antos CL, Li S, Wang Y, Olson EN, Wang DZ. Myocardin induces cardiomyocyte hypertrophy. Circulation research. 98(8) : 1089-97, 2006.
  • Liu ZP, Wang Z, Yanagisawa H, Olson EN. Phenotypic modulation of smooth muscle cells through interaction of Foxo4 and myocardin. Developmental cell. 9(2) : 261-70, 2005.
  • Cao D, Wang Z, Zhang CL, Oh J, Xing W, Li S, Richardson JA, Wang DZ, Olson EN. Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin. Molecular and cellular biology. 25(1) : 364-76, 2005.
  • Oh J, Wang Z, Wang DZ, Lien CL, Xing W, Olson EN. Target gene-specific modulation of myocardin activity by GATA transcription factors. Molecular and cellular biology. 24(19) : 8519-28, 2004.
  • Wang Z, Wang DZ, Hockemeyer D, McAnally J, Nordheim A, Olson EN. Myocardin and ternary complex factors compete for SRF to control smooth muscle gene expression. Nature. 428(6979) : 185-9, 2004.
  • Wang Z, Wang DZ, Pipes GC, Olson EN. Myocardin is a master regulator of smooth muscle gene expression. Proceedings of the National Academy of Sciences of the United States of America. 100(12) : 7129-34, 2003.
  • Li S, Wang DZ, Wang Z, Richardson JA, Olson EN. The serum response factor coactivator myocardin is required for vascular smooth muscle development. Proceedings of the National Academy of Sciences of the United States of America. 100(16) : 9366-70, 2003.
  • Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, Richardson JA, Nordheim A, Olson EN. Potentiation of serum response factor activity by a family of myocardin-related transcription factors. Proceedings of the National Academy of Sciences of the United States of America. 99(23) : 14855-60, 2002.
  • Wang D, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, Krieg PA, Olson EN. Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor. Cell. 105(7) : 851-62, 2001.
  • Shuzhen Liu, Preston Perez, Xue Sun, Ken Chen, Rojin Fatirkhorani, Jamila Mammadova, Zhigao Wang MLKL polymerization-induced lysosomal membrane permeabilization promotes necroptosis Cell Death & Differentiation. 31: 40-52, 2024.

Positions Held

  • Assistant Professor (Molecular Biology, UT Southwestern Medical Center 2012 - 2021)