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. In December 2014, Dr. Wang became an assistant professor in the Department 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.