Gang Yu, Ph.D. Titles and Appointments Professor Endowed Title Rosalee G. and James M. McConnell Professorship in Alzheimer's Disease Research; Thomas O. Hicks Scholar in Medical Research Schools Medical School | Graduate School Departments Neuroscience Graduate Programs Cell and Molecular Biology, Neuroscience Biography Gang Yu, Ph.D., is a Professor of Neuroscience at UT Southwestern Medical Center. He earned his Ph.D. in biochemistry and molecular biology at the University of Calgary and completed postdoctoral training in neurobiology at the University of Toronto before joining the UT Southwestern faculty in 2001. Dr. Yu’s research has made foundational contributions to Alzheimer’s disease biology while advancing understanding of cellular homeostasis and neurodegeneration. His early work was central to defining the gamma-secretase complex, a membrane-embedded protease essential for amyloid-β production and Notch signaling. He identified nicastrin as an essential component and substrate receptor, helped establish Aph-1 and Pen-2 as core subunits, and demonstrated that gamma-secretase is a discrete four-protein complex. These discoveries defined the complex’s molecular composition and assembly, as well as its mechanism of substrate recognition, and continue to guide mechanistic studies and the development of gamma-secretase modulators (GSMs) as potential disease-modifying treatments for Alzheimer’s disease. The Yu laboratory’s current research program is organized around two complementary themes: cellular homeostasis and tissue resilience. The cellular homeostasis program builds on the laboratory’s gamma-secretase research and investigates how vesicle, protein, RNA, and synaptic homeostasis preserve neuronal function—and how their disruption contributes to disease. The tissue resilience program integrates systems biology and deep proteomics of human brain tissue with genetically precise mouse models and studies of the amyloid plaque microenvironment to determine how Alzheimer’s disease-associated proteins and astrocyte–microglia signaling shape amyloid pathology and local tissue injury. By integrating these programs, the Yu laboratory seeks to define how amyloid-β-linked and amyloid-β-independent mechanisms converge to drive synaptic dysfunction, neuroinflammation, tau pathology, and neurodegeneration. Its long-term goal is to understand why some cells and tissues succumb to disease pathology while others remain resilient, and to translate those insights into new strategies for preserving brain function and advancing drug discovery. Dr. Yu has trained a number of graduate students and postdoctoral fellows who have gone on to independent faculty positions at universities and scientific careers in the pharmaceutical and biotechnology industries. The Yu laboratory is currently recruiting highly motivated graduate students and postdoctoral fellows interested in Alzheimer’s disease and neurodegeneration. Education Undergraduate Unlisted - International Colle (1988) Graduate School Northwestern Univ (1991) Graduate School University of Calgary - Canada (1996) Research Interest Alzheimer disease Amyloid plaque microenvironment Drug discovery Neurodegeneration Protein and cellular homeostasis The gamma-secretase complex Tissue resilience Publications Featured Publications Pan-neurodegeneration proteomics reveals disease subtypes and molecular signatures. Shrestha HK, Sun H, Yarbro JM, Lee D, Liu D, Wang E, McReynolds M, Zhang N, Xie B, Yang S, Yu K, Poudel S, Li Y, Yuan ZF, Kong D, Wang M, Wang Z, Niu M, Wang H, Zaman M, Wang J, Vanderwall DR, Sun Y, Wu Z, Chen PC, Bai B, High AA, Faura J, Liu C, Bennett DA, Johnson ECB, Seyfried NT, Levey AI, Haroutunian V, Serrano GE, Beach TG, DeTure M, Kanekiyo T, Petersen RC, Bu G, McLean PJ, Dickson DW, Rademakers R, Yu G, Wang X, Zhang B, Peng J, Cell 2026 Mar Midkine attenuates amyloid-β fibril assembly and plaque formation. Zaman M, Yang S, Huang Y, Yarbro JM, Hao Y, Wang Z, Liu D, Harper KE, Soliman H, Hemphill A, Harvey S, Pruett-Miller SM, Stewart V, Tanwar AS, Kalathur R, Grace CR, Turk M, Chittori S, Jiao Y, Wu Z, High AA, Wang X, Serrano GE, Beach TG, Yu G, Yang Y, Chen PC, Peng J, Nat Struct Mol Biol 2025 Aug Proteomic landscape of Alzheimer's disease: emerging technologies, advances and insights (2021 - 2025). Yarbro JM, Shrestha HK, Wang Z, Zhang X, Zaman M, Chu M, Wang X, Yu G, Peng J, Mol Neurodegener 2025 Jul 20 1 83 Human and mouse proteomics reveals the shared pathways in Alzheimer's disease and delayed protein turnover in the amyloidome. Yarbro JM, Han X, Dasgupta A, Yang K, Liu D, Shrestha HK, Zaman M, Wang Z, Yu K, Lee DG, Vanderwall D, Niu M, Sun H, Xie B, Chen PC, Jiao Y, Zhang X, Wu Z, Chepyala SR, Fu Y, Li Y, Yuan ZF, Wang X, Poudel S, Vagnerova B, He Q, Tang A, Ronaldson PT, Chang R, Yu G, Liu Y, Peng J, Nat Commun 2025 Feb 16 1 1533 Cytoplasmic retention of the DNA/RNA-binding protein FUS ameliorates organ fibrosis in mice. Chiusa M, Lee YA, Zhang MZ, Harris RC, Sherrill T, Lindner V, Brooks CR, Yu G, Fogo AB, Flynn CR, Zienkiewicz J, Hawiger J, Zent R, Pozzi A, J Clin Invest 2024 Mar 134 6 Alzheimer's disease-associated U1 snRNP splicing dysfunction causes neuronal hyperexcitability and cognitive impairment. Chen PC, Han X, Shaw TI, Fu Y, Sun H, Niu M, Wang Z, Jiao Y, Teubner BJW, Eddins D, Beloate LN, Bai B, Mertz J, Li Y, Cho JH, Wang X, Wu Z, Liu D, Poudel S, Yuan ZF, Mancieri A, Low J, Lee HM, Patton MH, Earls LR, Stewart E, Vogel P, Hui Y, Wan S, Bennett DA, Serrano GE, Beach TG, Dyer MA, Smeyne RJ, Moldoveanu T, Chen T, Wu G, Zakharenko SS, Yu G, Peng J, Nat Aging 2022 Oct 2 10 923-940 Breathing new life into the rational design of Alzheimer's therapeutics. Dries DR, Yu G, Cell 2021 Jan 184 2 296-298 Essential requirement for nicastrin in marginal zone and B-1 B cell development. Choi JH, Han J, Theodoropoulos PC, Zhong X, Wang J, Medler D, Ludwig S, Zhan X, Li X, Tang M, Gallagher T, Yu G, Beutler B, Proc. Natl. Acad. Sci. U.S.A. 2020 Feb Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression. Bai B, Wang X, Li Y, Chen PC, Yu K, Dey KK, Yarbro JM, Han X, Lutz BM, Rao S, Jiao Y, Sifford JM, Han J, Wang M, Tan H, Shaw TI, Cho JH, Zhou S, Wang H, Niu M, Mancieri A, Messler KA, Sun X, Wu Z, Pagala V, High AA, Bi W, Zhang H, Chi H, Haroutunian V, Zhang B, Beach TG, Yu G, Peng J, Neuron 2020 Jan Activity-dependent FUS dysregulation disrupts synaptic homeostasis. Sephton CF, Tang AA, Kulkarni A, West J, Brooks M, Stubblefield JJ, Liu Y, Zhang MQ, Green CB, Huber KM, Huang EJ, Herz J, Yu G Proc. Natl. Acad. Sci. U.S.A. 2014 Oct Results 1-10 of 34 1 2 3 4 Next Last Honors & Awards Award for Excellence in Postdoctoral Mentoring (2010) Ruth K. Broad Research Foundation Award (2006) Ruth Salta Junior Investigator Achievement Award (2005) Alzheimer Disease Research Award (2003) Natalie Ornish Award (2002) Thomas O. Hicks Scholar in Medical Research (2001) Memorial Frist/Jus Research Award (1998) Professional Associations/Affiliations American Society of Biochemistry and molecular biology (2010) Editorial Board, Journal of Biological Chemistry (2010-2016) Society for Neuroscience (2002)
