Yingfei Wang, Ph.D. Associate Professor School Medical School Department Pathology | Neurology Graduate Programs Genetics, Development and Disease, Neuroscience 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 Associate 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 neurodegeneration and cell death, especially a new type of cell death named PARthanatos (PARP-1-dependent cell death), using in vitro and in vivo models of neurological diseases including Alzheimer's disease and brain injury as well as human 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; Wang Y. et al., Molecular Psychiatry, 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 Cell death I Neurodegeneration Mitochondrial dysfunction I Oxidative stress PARP I DNA Damage I Aging-related genome instability Stroke I Alzheimer's disease I Traumatic brain injury Publications Featured Publications KDM6B cooperates with Tau and regulates synaptic plasticity and cognition via inducing VGLUT1/2. Wang Y, Khandelwal N, Liu S, Zhou M, Bao L, Wang JE, Kumar A, Xing C, Gibson JR, Wang Y, Mol Psychiatry 2022 Aug KDM6B promotes PARthanatos via suppression of O6-methylguanine DNA methyltransferase repair and sustained checkpoint response. Yang M, Wang C, Zhou M, Bao L, Wang Y, Kumar A, Xing C, Luo W, Wang Y, Nucleic Acids Res 2022 Jun Emerging role of PARP-1 and PARthanatos in ischemic stroke. Liu S, Luo W, Wang Y, J Neurochem 2022 Jan 160 1 74-87 MIF promotes neurodegeneration and cell death via its nuclease activity following traumatic brain injury. Ruan Z, Lu Q, Wang JE, Zhou M, Liu S, Zhang H, Durvasula A, Wang Y, Wang Y, Luo W, Wang Y, Cell Mol Life Sci 2021 Dec 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 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) ZMYND8 protects breast cancer stem cells against oxidative stress and ferroptosis through activation of NRF2. Luo M, Bao L, Xue Y, Zhu M, Kumar A, Xing C, Wang JE, Wang Y, Luo W, J Clin Invest 2024 Jan 134 6 Results 1-10 of 45 1 2 3 4 5 Next Last Books Featured Books 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 DOD(2024-2028) (2024) NIA R01 grant(2023-2028) (2023) 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 Associate Faculty Member of Faculty of 1000 Biology (2011-2012) Member of American Association for Cancer Research (AACR) (2015) Member of American Heart Association (AHA) (2012) Member of Society for Neuroscience (2007)
