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You-Wen He, MD, PhD

Professor of Immunology
Campus Mail: 335 Jones Building, 207 Resear, Box 3010 DUMC, Durham, NC 27710
Phone: (919) 613-7870
Email: he000004@mc.duke.edu

We study T cell biology in health and disease. Our current study is divided into two parts. Part I is to investigate T lymphocyte-mediated anti-caner immunity. We have found that host complement inhibits the cytokine IL-10 production in CD8+ tumor infiltrating lymphocytes through complement receptors C3aR and C5aR. Complement-deficient animals are resistant to tumor development in a T cell- and IL-10-dependent manner. CD8+ tumor infiltrating T cells express IL-10 when complement signaling is disabled. We found that tumor infiltrating lymphocytes from human cancers expanded with IL-2 plus IL-10 are potent tumor killers. Complement-mediated inhibition on antitumor immunity is independent of the PD-1/PD-L1 immune checkpoint pathway. Our findings suggest that complement receptors C3aR and C5aR expressed on CD8+ tumor infiltrating lymphocytes represent a novel class of immune checkpoints that needs to be targeted for tumor immunotherapy. Our current effort is to enhance cancer immunotherapy through several strategies. First, we investigate a combined blockade of complement signaling and anti-PD-1 to enhance the antitumor efficacy; second, we are studying the antitumor efficacy of a targeted delivery of IL-10 to antitumor CD8+ T cells by using anti-PD1-IL-10 or anti-CTLA-4-IL-10 fusion proteins; third, we are studying the tumor killing efficacy of addition of IL-10 in the expansion protocol of tumor infiltrating lymphocytes for adaptive cellular therapy.

Part II is to investigate the intracellular process termed autophagy in T lymphocyte function. Autophagy is a highly conserved self-digestion pathway that plays essential roles in maintaining the homeostasis of organelles, degrading long-lived proteins and recycling amino acids under starvation conditions. We have found that autophagy related molecules are expressed in T lymphocytes and autophagy occurs inside T lymphocytes. We have generated autophagy-deficient T lymphocytes in multiple genetic models and investigated the roles of autophagy in T lymphocytes. We found that autophagy plays a critical role in T lymphocyte function. Our current effort is to elucidate the molecular pathways by which TCR signal induces autophagy and the impact of autophagy on intracellular organelle homeostasis in dividing T cells.   

 

 

 

Education and Training

  • Senior Fellow, Immunology, University of Washington, 1996 - 2000
  • Ph.D., University of Miami, 1996
  • M.D., Fourth Military Medical University (China), 1986

Selected Publications

Zhao, BB, Zheng, SJ, Gong, LL, Wang, Y, Chen, CF, Jin, WJ, Zhang, D, Yuan, XH, Guo, J, Duan, ZP, and He, YW. "T Lymphocytes from Chronic HCV-Infected Patients Are Primed for Activation-Induced Apoptosis and Express Unique Pro-Apoptotic Gene Signature." PLoS ONE 8, no. 10 (October 10, 2013).

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He, MX, Wan, Y, and He, YW. "Role of the Autophagy Gene Atg5 in T Lymphocyte Survival and Proliferation." (October 1, 2013): 239-244. (Chapter)

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He, M-X, and He, Y-W. "A role for c-FLIP(L) in the regulation of apoptosis, autophagy, and necroptosis in T lymphocytes." Cell Death Differ 20, no. 2 (February 2013): 188-197.

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Dunkle, A, Dzhagalov, I, Gordy, C, and He, Y-W. "Transfer of CD8+ T cell memory using Bcl-2 as a marker." J Immunol 190, no. 3 (February 1, 2013): 940-947.

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Jia, W, He, M-X, McLeod, IX, and He, Y-W. "Autophagy, a novel pathway to regulate calcium mobilization in T lymphocytes." Frontiers in Immunology 4, no. JUL (2013).

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He, M-X, and He, Y-W. "CFLAR/c-FLIPL: A star in the autophagy, apoptosis and necroptosis alliance." Autophagy 9, no. 5 (2013): 791-793.

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Zhang, Z-N, Xu, J-J, Fu, Y-J, Liu, J, Jiang, Y-J, Cui, H-L, Zhao, B, Sun, H, He, Y-W, Li, Q-J, and Shang, H. "Transcriptomic analysis of peripheral blood mononuclear cells in rapid progressors in early HIV infection identifies a signature closely correlated with disease progression." Clinical Chemistry 59, no. 8 (2013): 1175-1186.

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Piao, X, Komazawa-Sakon, S, Nishina, T, Koike, M, Piao, J-H, Ehlken, H, Kurihara, H, Hara, M, Van Rooijen, N, Schütz, G, Ohmuraya, M, Uchiyama, Y, Yagita, H, Okumura, K, He, Y-W, and Nakano, H. "c-FLIP maintains tissue homeostasis by preventing apoptosis and programmed necrosis. (Published online)" Sci Signal 5, no. 255 (December 18, 2012): ra93-.

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McLeod, IX, and He, Y-W. "Editorial: TRPV1: how thymocytes sense stress and respond with autophagy." J Leukoc Biol 92, no. 3 (September 2012): 409-411.

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McLeod, IX, Jia, W, and He, Y-W. "The contribution of autophagy to lymphocyte survival and homeostasis." Immunol Rev 249, no. 1 (September 2012): 195-204. (Review)

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Wang, Y, Wang, XD, Lapi, E, Sullivan, A, Jia, W, He, Y-W, Ratnayaka, I, Zhong, S, Goldin, RD, Goemans, CG, Tolkovsky, AM, and Lu, X. "Autophagic activity dictates the cellular response to oncogenic RAS." Proc Natl Acad Sci U S A 109, no. 33 (August 14, 2012): 13325-13330.

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Paul, S, Kashyap, AK, Jia, W, He, Y-W, and Schaefer, BC. "Selective autophagy of the adaptor protein Bcl10 modulates T cell receptor activation of NF-κB." Immunity 36, no. 6 (June 29, 2012): 947-958.

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Jin, W-J, Chen, C-F, Liao, H-Y, Gong, L-L, Yuan, X-H, Zhao, B-B, Zhang, D, Feng, X, Liu, J-J, Wang, Y, Chen, G-F, Yan, H-P, and He, Y-W. "Downregulation of the AU-rich RNA-binding protein ZFP36 in chronic HBV patients: implications for anti-inflammatory therapy." PLoS One 7, no. 3 (2012): e33356-.

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He, M-X, McLeod, IX, Jia, W, and He, Y-W. "Macroautophagy in T lymphocyte development and function. (Published online)" Front Immunol 3 (2012): 22-.

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Gordy, C, and He, Y-W. "The crosstalk between autophagy and apoptosis: Where does this lead?." Protein and Cell 3, no. 1 (2012): 17-27.

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