Dr. Wang received his Ph.D. degree in 2004 in Dr. Eric Olson's lab at UT Southwestern Medical Center. He then joined the lab of Dr. Xiaodong Wang across the bridge for his post-doctoral training. In 2012, he became an assistant professor in the Department of Molecular Biology.
Necrosis is a process clearly distinguished from apoptosis and is implicated in many human pathological conditions, including infections, ischemic injuries, neurodegeneration and cancer. However, the molecular mechanisms of necrosis remain largely unknown. Using a combination of chemical genetics and biochemical approaches, Dr. Wang delineated the TNF-a-induced necrotic pathway into distinct steps and identified the mitochondrial protein phosphatase PGAM5 as a central player. PGAM5 also plays key roles in reactive oxygen species (ROS) and calcium overload induced necrosis. This research brought new insights into necrotic cell death pathways and identified many chemical inhibitors of necrosis, which potentially will lead to therapeutic strategies to treat necrosis-related diseases. Activation of the necrotic pathways in tumors that are highly resistant to apoptosis will be a novel direction in cancer treatment.
At UT Southwestern, Dr. Wang will continue investigating the mechanisms of necrotic cell death, especially the executioners of the process, using unique chemical and biological tools. The in vivo functions of the key components of the necrosis pathways will also be investigated using mouse genetics and chemical biology.The ultimate goal of his research is to apply the knowledge to develop novel pharmacological interventions to treat necrosis-related human diseases.
- Molecular mechanisms of necrotic cell death
- Small molecule inhibitors or activators of necrotic cell death
- The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways.
- Wang Z, Jiang H, Chen S, Du F, Wang X Cell 2012 Jan 148 1-2 228-43
- Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase.
- Sun L, Wang H, Wang Z, He S, Chen S, Liao D, Wang L, Yan J, Liu W, Lei X, Wang X Cell 2012 Jan 148 1-2 213-27
- Myocardin and ternary complex factors compete for SRF to control smooth muscle gene expression.
- Wang Z, Wang DZ, Hockemeyer D, McAnally J, Nordheim A, Olson EN Nature 2004 Mar 428 6979 185-9
- Myocardin is a master regulator of smooth muscle gene expression.
- Wang Z, Wang DZ, Pipes GC, Olson EN Proc. Natl. Acad. Sci. U.S.A. 2003 Jun 100 12 7129-34
- Phenotypic modulation of smooth muscle cells through interaction of Foxo4 and myocardin.
- Liu ZP, Wang Z, Yanagisawa H, Olson EN Dev. Cell 2005 Aug 9 2 261-70
- Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin.
- Cao D, Wang Z, Zhang CL, Oh J, Xing W, Li S, Richardson JA, Wang DZ, Olson EN Mol. Cell. Biol. 2005 Jan 25 1 364-76
- Target gene-specific modulation of myocardin activity by GATA transcription factors.
- Oh J, Wang Z, Wang DZ, Lien CL, Xing W, Olson EN Mol. Cell. Biol. 2004 Oct 24 19 8519-28
- The serum response factor coactivator myocardin is required for vascular smooth muscle development.
- Li S, Wang DZ, Wang Z, Richardson JA, Olson EN Proc. Natl. Acad. Sci. U.S.A. 2003 Aug 100 16 9366-70
- Potentiation of serum response factor activity by a family of myocardin-related transcription factors.
- Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, Richardson JA, Nordheim A, Olson EN Proc. Natl. Acad. Sci. U.S.A. 2002 Nov 99 23 14855-60
- Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor.
- Wang D, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, Krieg PA, Olson EN Cell 2001 Jun 105 7 851-62
Honors & Awards
- CPRIT Scholar in Cancer Research
Cancer Prevention and Research Institute of Texas (2012)
- Endowed Scholar in Biomedical Research
UT Southwestern Medical Center at Dallas (2012)
- HHMI Post-doctoral Fellowship
Howard Hughes Medical Institute (2008)
- Cancer Biology Graduate Program (2012)
- Genetics and Development Graduate Program (2012)