Microbiology and Immunology
The Charles Gordon Smith Professor for HIV Research, Laboratory of Viral Pathogenesis and Immunotherapy; Director, Division of Virology, Pathogenesis and Cancer, Institute of Human Virology// Professor, Departments of Pharmacology, Microbiology & Immunology// Member, Greenebaum Comprehensive Cancer Center
725 West Lombard St.
Education and Training
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA
Postdoctoral Fellow, Immunology and Stem Cell Biology
Departments of Pathology and Developmental Biology, HHMI, School of Medicine, Stanford University, Palo Alto, CA
Dr. Lishan Su grew up in Qingdao (aka Tsingtao), China. He received his Ph.D. degree in Virology from Harvard University (Herpes Simplex Virus-1) and did his post-doctoral training in Immunology and Stem Cell Biology at Stanford University (T cells and blood stem cells). He then worked as a senior scientist in a biotech company SyStemix/Sandoz (Novartis), focusing on blood stem cell-based HIV-1 gene therapy in humanized mice and in patients. Until Oct. 2020, Dr. Su was a faculty member in the Lineberger Comprehensive Cancer Center and Professor in the Department of Microbiology & Immunology at University of North Carolina-Chapel Hill. He was elected as a Fellow of American Association for the Advancement of Science in 2012. After joining The Institute of Human Virology at UMSOM in Oct. 2020, Dr. Lishan Su continues his research program to use HIV and HBV viruses as probes to dissect human immunity and inflammatory diseases, and to develop antibody and cell-based drugs targeting novel immune cells and signaling pathways. The laboratory thus studies HIV-1 and HBV (Virology) and how their interactions with human innate immune cells cause inflammatory diseases (Immunology) using various cell and organoid cultures, as well as humanized mouse models. In addition, they are developing novel drugs including antibodies, CAR-T and therapeutic vaccines (Immunotherapy) to treat human inflammatory diseases including virus infection and cancer.
Immunology, virology, immunotherapy, humanized mice, CAR-T
Guo, H, et al. (2021). "Multi-omics analyses reveal that HIV-1 alters CD4 T cell immunometabolism to fuel virus replication." Nature Immunology (in press)
- Barrat, F. J. and Su# (2019). "A pathogenic role of plasmacytoid dendritic cells in autoimmunity and chronic viral infection." J Exp Med 216(9): 1974-1985.
- Cheng, L., Q. Wang, G. Li, R. Banga, J. Ma, H. Yu, F. Yasui, Z. Zhang, G. Pantaleo, M. Perreau, S. Zurawski, G. Zurawski, Y. Levy and L. Su (2018). "TLR3 agonist and CD40-targeting vaccination induces immune responses and reduces HIV-1 reservoirs." J Clin Invest 128(10): 4387-4396.
- Lv, L., Q. Wang, Y. Xu, L. C. Tsao, T. Nakagawa, H. Guo, Su# and Y. Xiong (2018). "Vpr Targets TET2 for Degradation by CRL4(VprBP) E3 Ligase to Sustain IL-6 Expression and Enhance HIV-1 Replication." Mol Cell 70(5): 961-970 e965.
- Cheng L, Ma J, Li J, Li D, Li G, Li F, Zhang Q, Yu H, Yasui F, Ye C, Tsao LC, Hu Z, Su L#, Zhang L. (2017). Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs. J Clin Invest. 127(1):269-279.
- Murphy, C. M., Y. Xu, F. Li, K. Nio, N. Reszka-Blanco, X. Li, Y. Wu, Y. Yu, Y. Xiong and L. Su (2016). "Hepatitis B Virus X Protein Promotes Degradation of SMC5/6 to Enhance HBV Replication." Cell Rep 16(11): 2846-2854.
- Washburn, M. L., M. T. Bility, L. Zhang, G. I. Kovalev, A. Buntzman, J. A. Frelinger, W. Barry, A. Ploss, C. M. Rice and Su (2011). "A humanized mouse model to study hepatitis C virus infection, immune response, and liver disease." Gastroenterology 140(4): 1334-1344.
- Coffield, V. M., Q. Jiang and Su (2003). "A genetic approach to inactivating chemokine receptors using a modified viral protein." Nat Biotechnol 21(11): 1321-1327.
- Su, L. (2019). "Pathogenic Role of Type I Interferons in HIV-Induced Immune Impairments in Humanized Mice." Curr HIV/AIDS Rep 16(3): 224-229.
- Allen TM, Brehm MA, Bridges S, Ferguson S, Kumar P, Mirochnitchenko O, Palucka K, Pelanda R, Sanders-Beer B, Shultz LD, Su L, PrabhuDas M. (2019) Humanized immune system mouse models: progress, challenges and opportunities. Nat Immunol. 2019 Jun 3. doi: 10.1038/s41590-019-0416-z. PMID:31160798
- Su, L. (2019). "Disruption of HBx-DDB1 by NTZ: New Mechanistic Insight Into an Old Drug With Broad Anti-infective Activities." Cell Mol Gastroenterol Hepatol 7(2): 289-290.
- Zhao, J., L. Cheng, H. Wang, H. Yu, B. Tu, Q. Fu, G. Li, Q. Wang, Y. Sun, X. Zhang, Z. Liu, W. Chen, L. Zhang, Su# and Z. Zhang (2018). "Infection and depletion of CD4+ group-1 innate lymphoid cells by HIV-1 via type-I interferon pathway." PLoS Pathog 14(1): e1006819.
- Bi, W., W. Xu, L. Cheng, J. Xue, Q. Wang, F. Yu, S. Xia, Q. Wang, G. Li, C. Qin, L. Lu, Su# and S. Jiang (2019). "IgG Fc-binding motif-conjugated HIV-1 fusion inhibitor exhibits improved potency and in vivo half-life: Potential application in combination with broad neutralizing antibodies." PLoS Pathog 15(12): e1008082.
- Li, G., Z. Zhang, N. Reszka-Blanco, F. Li, L. Chi, J. Ma, J. Jeffrey, L. Cheng and Su (2019). "Specific Activation In Vivo of HIV-1 by a Bromodomain Inhibitor from Monocytic Cells in Humanized Mice under Antiretroviral Therapy." J Virol 93(12).
- Li, T., Y. Yang, H. Song, H. Li, A. Cui, Y. Liu, Su, I. N. Crispe and Z. Tu (2019). "Activated NK cells kill hepatic stellate cells via p38/PI3K signaling in a TRAIL-involved degranulation manner." J Leukoc Biol 105(4): 695-704.
- Nunoya, J. I., M. Masuda, C. Ye and Su (2019). "Chimeric Antigen Receptor T Cell Bearing Herpes Virus Entry Mediator Co-stimulatory Signal Domain Exhibits High Functional Potency." Mol Ther Oncolytics 14: 27-37.
- Song, H., G. Tan, Y. Yang, A. Cui, H. Li, T. Li, Z. Wu, M. Yang, G. Lv, X. Chi, J. Niu, K. Zhu, I. N. Crispe, Su and Z. Tu (2019). "Hepatitis B Virus-Induced Imbalance of Inflammatory and Antiviral Signaling by Differential Phosphorylation of STAT1 in Human Monocytes." J Immunol 202(8): 2266-2275.
- Tan, G., Z. Yi, H. Song, F. Xu, F. Li, R. Aliyari, H. Zhang, P. Du, Y. Ding, J. Niu, X. Wang, Su, F. X. Qin and G. Cheng (2019). "Type-I-IFN-Stimulated Gene TRIM5gamma Inhibits HBV Replication by Promoting HBx Degradation." Cell Rep 29(11): 3551-3563 e3553.
- Wang, Q. and Su (2019). "Vpr Enhances HIV-1 Env Processing and Virion Infectivity in Macrophages by Modulating TET2-Dependent IFITM3 Expression." mBio 10(4).
- Cheng, L., H. Yu, J. A. Wrobel, G. Li, P. Liu, Z. Hu, X. N. Xu and Su (2020). "Identification of pathogenic TRAIL-expressing innate immune cells during HIV-1 infection in humanized mice by scRNA-Seq." JCI Insight 5(11).
- Liu, S. L., L. J. Saif, S. R. Weiss and Su (2020). "No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2." Emerg Microbes Infect 9(1): 505-507.
- Sun, C., P. Shou, H. Du, K. Hirabayashi, Y. Chen, L. E. Herring, S. Ahn, Y. Xu, K. Suzuki, G. Li, O. Tsahouridis, Su, B. Savoldo and G. Dotti (2020). "THEMIS-SHP1 Recruitment by 4-1BB Tunes LCK-Mediated Priming of Chimeric Antigen Receptor-Redirected T Cells." Cancer Cell 37(2): 216-225 e216.
- Whitacre, D. C., C. J. Peters, C. Sureau, K. Nio, F. Li, Su, J. E. Jones, M. Isogawa, M. Sallberg, L. Frelin, D. L. Peterson and D. R. Milich (2020). "Designing a therapeutic hepatitis B vaccine to circumvent immune tolerance." Hum Vaccin Immunother 16(2): 251-268.
- Godot V, Tcherakian C, Gil L, Cervera-Marzal I, Li G, Cheng L, Ortonne N, Lelièvre JD, Pantaleo G, Fenwick C, Centlivre M, Mouquet H, Cardinaud S, Zurawski SM, Zurawski G, Milpied P, Su L, Lévy Y. (2020). "TLR-9 agonist and CD40-targeting vaccination induces HIV-1 envelope-specific B cells with a diversified immunoglobulin repertoire in humanized mice."PLoS Pathog. 2020 Nov 30;16(11):e1009025.
- Zhang Y, Ma Z, Wang Y, Boyer J, Ni G, Cheng L, Su S, Zhang Z, Zhu Z, Qian J, Su L, Zhang Q, Damania B, Liu P. (2020).Streptavidin Promotes DNA Binding and Activation of cGAS to Enhance Innate Immunity. iScience. 23(9):101463.
- Guo Z, Wang G, Wu B, Chou WC, Cheng L, Zhou C, Lou J, Wu D, Su L, Zheng J, Ting JP, Wan YY. (2020) ".DCAF1 regulates Treg senescence via the ROS axis during immunological aging." J Clin Invest. 130(11):5893-5908.
- Lichtman EI, Du H, Shou P, Song F, Suzuki K, Ahn S, Li G, Ferrone S, Su L, Savoldo B, Dotti G. (2021).Preclinical Evaluation of B7-H3-Specific Chimeric Antigen Receptor T cells for the Treatment of Acute Myeloid Leukemia.Clin Cancer Res. 2021 Feb 2:clincanres.2540.2020.
My research laboratory has focused on several areas of human immunology and virology, particularly in studying human immuno-pathology of chronic virus infections. My group was one of the first to use humanized mouse models to study HIV-1 infection and pathogenesis, and to develop human blood stem cell-based gene therapy for AIDS. My lab has identified novel virological and immunological mechanisms of HIV-1 and HBV pathogenesis. In recent years, my group has discovered and focused on the pDC-interferon-macrophage axis in the immuno-pathogenesis and therapy of chronic HIV & HBV infections. The group has also started investigation of the pDC-IFN-M2 axis in tumor microenvironments (TME) and in cancer immune therapy. After joining The Institute of Human Virology at UMSOM in Oct. 2020, we continue the research programs to use HIV and HBV viruses as probes to dissect human immunity and inflammatory diseases, and to develop antibody and cell-based drugs targeting novel immune cells and signaling pathways. The laboratory thus studies HIV-1 and HBV (Virology) and how their interactions with human innate immune cells cause inflammatory diseases (Immunology) using various cell and organoid cultures, as well as humanized mouse models. In addition, we are developing novel drugs including antibodies, CAR-T and therapeutic vaccines (Immunotherapy) to treat human inflammatory diseases including virus infection and cancer.
2012- Fellow of American Association for the Advancement of Science (AAAS)
1998-2002 Jefferson Pilot Award
1997-1999 March of Dimes Basil O’Connor Scholar Award
1989-1992 Fellow of the Irvington Institute for Medical Research
1982-1985 Harvard Pre-Doctoral Fellowship (China-US Biochem. Exam/Admi. Program)
R01DK119937 (Su: PI) 9/1/18-8/31/23
National Institutes of Health, Immune Mechanisms of Elevated Liver Disease During HIV Infection
We will elucidate the mechanisms by which HIV infection contributes to liver disease progression and develop novel therapeutics for preventing or treating HIV-associated liver diseases.
R01 AI127346 (Su: contact PI/Xiong) 09/01/16 - 08/31/21
NIH: HIV-1 Vpr Disrupts the IFN-TET-ISG Pathway to Promote HIV-1 Infection and Persistence
The goal of the project is to elucidate how HIV Vpr targets the TET-FIN-ISG pathway to promote HIV infection and pathogenesis.
Role: Contact PI of multi-PI RO1
R01AI134631 (Su: contact PI/Bosinger/Amara) 7/1/18-6/30/23
National Inst. of Health: Modulating pDC/IFN to reverse inflammation, improve immune recovery and control HIV-1 reservoirs
The long-term goal of this project is to elucidate the mechanism of pDC/IFN-induced immune suppression during persistent HIV infection, and the role of pDC/IFN-I in HIV reservoir persistence.
Role: Contact PI of multi-PI RO1
R01AI138797 (Su: contact PI/Ploss) 10/1/18-9/30/23
National Inst. of Health,
Modeling immune impairments and pathogenesis in novel humanized mice for HBV-HIV co-infection
The proposed work will not only yield a new and innovative humanized mouse model for HBV-HIV co-infection but also addresses critical questions related to immune functionality and pathogenesis.
Role: Contact PI of multi-PI RO1
P01-CA019014 (Damania) 5/1/97-6/30/21
NIH/NCI: Herpesviral, Oncogenesis, Latency and Reactivation: Project 3 - Modulation of Host Cell Biology by KSHV
In this application, we propose to determine how cellular and viral proteins promote endothelial cell migration, angiogenesis and survival of the infected cell and how this shapes the tumor microenvironment.
R01 AI136715 (Chung) 9/1/17-8/31/22
NIH/NIAID: HIV, HCV, HIPPO and Liver Disease Progression
The proposed studies will be of high impact, since they will greatly aid our efforts to develop effective interventions to halt or reverse liver disease progression among HCV-HIV coinfected persons
Role: PI of UNC subcontract (MGH Subcontract)
R01AI136948 (Chang) 4/1/18-3/31/23
NIH/NIAID: Role of IFNe in immune modulation and HIV infection
The results of this study will provide a better understanding of the interplay between IFNe, immune responses and HIV infection, will have clinical implications for prevention and treatment.
Role: PI of UNC subcontract (Rutgers Subcontract, years 3-5)
R01AI1393290 (Hioe) 6/7/18-5/31/23
National Inst.of Health: Harnessing Abs Specific for Immunogenic and Conserved Env Epitopes to Protect Against HIV
This proposal describes research to evaluate the contributions to protection against HIV transmission made by antibodies against immunogenic conserved sites on the HIV envelope.
Role: PI of UNC subcontract (ISMMS Subcontract)
R01AI139511 (Feng) 9/1/18-8/31/23
National Inst.of Health, Mechanism for spread of a quasi-enveloped hepatotropic virus
This work will fill gaps in our understanding of the quasi-envelopment processes and how it influences virus spread, pathogenesis and immunity, and it will likely identify novel targets for therapeutic intervention.
Role: PI UNC subcontract (RINCH/OSU Subcontract)
R01CA243543-01 (Dotti) 9/1/19 – 8/31/24
National Inst. of Health: Cellular Immunotherapy of Ovarian Cancer
The proposed study will explore whether immune cells called natural killer T cells (NKTs) upon genetic modification can attack OC cells and other cells of the tumor microenvironment.
Humanized mice, human immunology and HIV/HBV virology