Liang Shan, PhD
- BS: Nankai University, Tianjin, China (2003)
- MS: Fudan University, Shanghai, China (2007)
- PhD - Focus: HIV latency and CD8 T Cell response: Johns Hopkins University, Baltimore, MD (2012)
- Postdoctural Fellow - Focus: Development of novel humanized mouse models: Yale University, New Haven, CT (2017)
To date, no broadly applicable strategy has been developed to prevent or eradicate HIV-1 infection. Our research is hampered by the limited ability to investigate HIV-1 infection in tissues and the lack of understanding of antiviral immune responses in vivo. Numerous efforts have been made to develop humanized mouse models of HIV-1 infection to study in vivo human immune response and to assess the effectiveness of vaccination and eradication strategies. However, several major issues in commonly used humanized mouse models have prevented us from achieving these goals: 1) abortive human myelopoiesis prevents us from investigating HIV-1 infection in monocytes and tissue macrophages, as well as their responses to infection; 2) deficient repopulation of adult or patient CD34+ cells prevents us from reconstituting patient-derived immune system in mice; 3) inefficient human NK cell development prevents us from exploring NK cell-mediated viral inhibition strategies; 4) erroneous thymic human T cell selection driven by mouse MHC molecules prevents us from inducing and examining human MHC-restricted T cell response and human MHC- specific viral escape mutations; 5) lack of human T cell homeostasis due to the absence of human IL-7 and IL-15 in lymphoid tissues prevents us from understanding the stability and homeostatic proliferation of the viral reservoirs.
To address these issues, we have generated novel mouse models that contain multiple human gene knock-ins to improve human hematopoiesis and maturation and survival of human immune cells in the mouse system. Using the novel humanized mouse models, my lab will focus on the following topics:
- Characterization of HIV-1 latent reservoir in tissue-resident CD4+ T cells and tissue macrophages
- Development of CTL-based strategies to eliminate circulating and tissue residing latent reservoirs for HIV-1
- Development of antibody-based immunological approaches to control HIV-1 infection and eliminate latent HIV-1
- Generation of patient-derived humanized mouse models as a pre-clinical platform to evaluate vaccine efficacies
- Shan L*, Deng K*, Gao H, Xing S, Capoferri AA, Durand CM, Rabi SA, Laird GM, Kim M, Hosmane NN, Yang HC, Zhang H, Margolick JB, Li L, Cai W, Ke R, Flavell RA, Siliciano JD, Siliciano RF. Transcriptional Reprogramming during Effector-to-Memory Transition Renders CD4+ T Cells Permissive for Latent HIV-1 Infection. Immunity. 2017 Oct 17;47(4):766-775. * equal contribution.
- Herndler-Brandstetter D*, Shan L*, Yao Y, Stecher C, Plajer V, Lietzenmayer M, Strowig T, de Zoete MR, Palm NW, Chen J, Blish CA, Frleta D, Gurer C, Macdonald LE, Murphy AJ, Yancopoulos GD, Montgomery RR, Flavell RA. Humanized mouse model supports development, function, and tissue residency of human natural killer cells. Proc Natl Acad Sci 2017 Oct 25. * equal contribution.
- Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Bhiaur G, Lai J, McHugh HL, Hao H, Zhang H, Margolick JB, Gurer C, Murphy AJ, Valenzuela DM, Yancopoulos GD, Deeks SG, Strowig T, Kumar P, Siliciano JD, Salzberg SL, Flavell RA#,Shan L.#, Siliciano RF#. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature. 2015 Jan 15;517(7534):381-5. # Co-corresponding author.
- Shan, L., Deng K, Shroff NS, Durand CM, Rabi SA, Yang HC, Zhang H, Margolick JB, Blankson JN, Siliciano RF. Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity. 2012 Mar. 36(3): 491-501
Additional Languages Spoken: Chinese