Dr. Yingfei Wang obtained her Ph.D. degree in Neuroscience at the University of Magdeburg in Germany and completed her postdoctoral training at the Johns Hopkins School of Medicine. Currently Dr. Wang is an Assistant Professor in the Departments of Pathology and Neurology at UT Southwestern.
Dr. Wang studies the molecular, cellular and metabolic mechanisms of a new type of cell death named PARthanatos (PARP-1-dependent cell death) using in vitro and in vivo models of neurological diseases and cancers. Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme in response to DNA damage/oxidative stress and plays an important role in cell death through a caspase-independent manner in neurodegeneration, ischemia-reperfusion injury, glutamate excitotoxicity and various inflammatory responses, as well as other non-neurological diseases like alkylating agent-induced cancer cell death. PARP-1 is a central player of PARthanatos and apoptosis-inducing factor (AIF) is the key mediator of PARthantos. We recently identified macrophage migration inhibitory factor (MIF) as a novel PARP-1 activity associated nuclease (PAAN) (Wang Y et al., Nature Communications, 2021) and the executor of PARthanatic cell death (Wang Y., et al. Science, 2016). We also identified a novel AIF3 splicing isoform, which is induced under pathological conditions and triggers mitochondrial dysfunction and neurodegeneration (Liu S., et al. Molecular Neurodegeneration, 2021). Our studies have made significant contributions in understanding PARthanatos in ischemic brain injury and neurodegenerative diseases. Currently, our lab is using a combination of tools, including epigenetics, bioinformatics, proteomics and mouse genetics, to understand the cell signaling and regulation of PARP-1 dependent DNA damage and cell death in neurological diseases as well as human cancers. Our research topics include 1) AIF3-mediated mitochondrial dysfunction and neurodegeneration; 2) PARP1-3 biological functions in brain and their role in PARthanatos under ischemia/hypoxia; 3) HIF biological functions in regulating PARthanatos in brain and cancers; 4) PARP/AIF-mediated metabolic dysregulation in PARthanatos cell death; 5) DNA damage- and oxidative stress-induced PARthanatic cell death in neurons and cancer cells. Our overall goals are to identify novel therapeutic targets and translate the knowledge to prevent/delay neuron loss but enhance cancer cell death.
- Brain injury
- Mitochondrial dysfunction
- PARP-1 and DNA Damage
- PARthanatic Cell Death
- MIF is a 3' flap nuclease that facilitates DNA replication and promotes tumor growth.
- Wang Y, Chen Y, Wang C, Yang M, Wang Y, Bao L, Wang JE, Kim B, Chan KY, Xu W, Capota E, Ortega J, Nijhawan D, Li GM, Luo W, Wang Y, Nat Commun 2021 05 12 1 2954
- AIF3 splicing switch triggers neurodegeneration.
- Liu S, Zhou M, Ruan Z, Wang Y, Chang C, Sasaki M, Rajaram V, Lemoff A, Nambiar K, Wang JE, Hatanpaa KJ, Luo W, Dawson TM, Dawson VL, Wang Y, Mol Neurodegener 2021 Apr 16 1 25
- ZMYND8 expression in breast cancer cells blocks T-lymphocyte surveillance to promote tumor growth.
- Wang Y, Luo M, Chen Y, Wang Y, Zhang B, Ren Z, Bao L, Wang Y, Wang JE, Fu YX, Luo W, Wang Y, Cancer Res 2020 Nov
- CHD4 promotes breast cancer progression as a coactivator of hypoxia-inducible factors.
- Wang Y, Chen Y, Zhang B, Bao L, Wang JE, Kumar A, Xing C, Wang Y*, Luo W*. Cancer Res. 2020 80 3880-3891. (*corresponding author).
- PARP-1 and its associated nucleases in DNA damage response.
- Wang Y, Luo W, Wang Y, DNA Repair (Amst.) 2019 Jul 102651
- A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1
- Wang Y*, An R, Umanah GK, Park H, Nambiar K, Eacker SM, Kim BW, Bao L, Harraz MM, Chang C, Chen R, Wang JE, Kam T, Jeong JS, Xie Z, Neifert S, Qian J, Andrabi SA, Blackshaw S, Zhu H, Song H, Ming GL, Dawson VL*, Dawson TM* Science 2016 PMID: 27846469 (* Corresponding authors)
- Poly(ADP-ribose) (PAR) binding to apoptosis-inducing factor is critical for PAR polymerase-1-dependent cell death (parthanatos).
- Wang Y, Kim NS, Haince JF, Kang HC, David KK, Andrabi SA, Poirier GG, Dawson VL, Dawson TM Sci Signal 2011 4 167 ra20
- Poly(ADP-ribose) signals to mitochondrial AIF: a key event in parthanatos.
- Wang Y, Dawson VL, Dawson TM Exp. Neurol. 2009 Aug 218 2 193-202
- LncIHAT Is Induced by Hypoxia-Inducible Factor 1 and Promotes Breast Cancer Progression.
- Chen L, Bao L, Niu Y, Wang JE, Kumar A, Xing C, Wang Y, Luo W, Mol Cancer Res 2020 Dec
- Multifaceted role of branched-chain amino acid metabolism in cancer.
- Peng H, Wang Y, Luo W, Oncogene 2020 Oct 39 44 6747-6756
The role of thrombin and thrombin receptors in the brain.. In Thrombin: Physiology and Disease
Luo W, Wang Y, Reiser G. (2008). Springer Verlag
Honors & Awards
- NIA R01 grant
- CPRIT HIHR Award
- R35 Maximizing Investigators Research Award
- Welch Research Award
- Darrell K Royal (DKR) Research Award
- Texas Institute for Brain injury and Repair (TIBIR) Pilot Grant
- UT Rising Star Award
- American Heart Association (AHA) National Scientist Development Grant Award
- NIH Pathway to Independence Award (Parent K99/R00)
- American Heart Association (AHA) Postdoctoral Fellowship Award
- Chinese Government Award for Outstanding Student Abroad
- Summa cum laude for Ph.D dissertation
- German Research Foundation DFG Scholarship
- Member of American Association for Cancer Research (AACR) (2015)
- Member of American Heart Association (AHA) (2012)
- Associate Faculty Member of Faculty of 1000 Biology (2011-2012)
- Member of Society for Neuroscience (2007)