Biography

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 and Investigator of Peter O'Donnell Jr. Brain Institute 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; Ruan Z., et al., Cell Mol Life Sci 2021). 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. Moreover, we extend PARthanatos research from neurological disease models to human cancers. We identified an epigenetic factor KDM6B as a novel regulator to control and switch PARP-1 functions between DNA repair and PARthanatic cell death (Yang M. et al., Nucleic Acids Res. 2022). Our studies revealed that PARP-1 functions are highly context-dependent (Wang Y et al., Nature Communications, 2021). Currently, our lab is using a combination of tools, including epigenetics, bioinformatics, proteomics and mouse genetics, to further 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 PARthanatic 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.

Research Interest

  • Brain injury
  • Cancer
  • Mitochondrial dysfunction
  • Neurodegeneration
  • PARP-1 and DNA Damage
  • PARthanatic Cell Death

Publications

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Books

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Honors & Awards

  • NIA R01 grant
    (2019-2024)
  • CPRIT HIHR Award
    (2017-2020)
  • R35 Maximizing Investigator's Research Award
    (2017-2023)
  • Welch Research Award
    (2017-2020)
  • Darrell K Royal (DKR) Research Fund for Alzheimer's disease
    (2015-2019)
  • NIH Pathway to Independence Award-R00
    (2015-2019)
  • Texas Institute for Brain injury and Repair (TIBIR) Pilot Grant
    (2015-2017)
  • UT Rising Star Award
    (2014-2017)
  • American Heart Association (AHA) National Scientist Development Grant Award
    (2012)
  • NIH Pathway to Independence Award-K99
    (2012-2014)
  • American Heart Association (AHA) Postdoctoral Fellowship Award
    (2008-2010)
  • Chinese Government Award for Outstanding Student Abroad
    (2007)
  • Summa cum laude for Ph.D dissertation
    (2007)
  • German Research Foundation DFG Scholarship
    (2002-2005)

Professional Associations/Affiliations

  • 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)