1993年起在何大一教授領導的美國艾倫.戴蒙德愛滋病研究中心（Aaron Diamond AIDS Research Center），主要從事 "HIV感染者治療前後體內病毒學基因變異、宿主基因多態性和免疫學特徵"等課題的研究。首先報導了人體不同細胞中HIV-1協同受體CCR5和CXCR4的分布特點，發現T淋巴細胞群表面協同受體的表達水平最高。同時指出HIV-1病毒亞型與協同受體CCR5和CXCR4之間相互結合的關係，提出了是病毒表型而不是病毒基因型決定了病毒與協同受體CCR5或CXCR4結合。
此外他在何大一教授指導下，通過長期觀察抗病毒治療的愛滋病患者體內的靜止細胞中儲藏的殘留HIV的動態過程，提出了病毒複製及其動態變化的模型，為徹底改進抗愛滋病的藥物治療的方針策略提供了科學的依據。研究論文分別發表在臨床醫學權威雜誌"New England J. Medicine"、"Nature"等，連續五年被SCI檢索為引用頻次為國際上最高的前五名論文之列。
這些成果為目前廣泛推廣的愛滋病抗病毒治療後的免疫重建模式奠定了可靠的定量依據。同時對進一步的開展藥物治療與免疫治療相結合的治療方案提供了科學的線索。這些病毒學及免疫學定量方法，對於HIV/AIDS臨床治療有著直接的指導意義。近年來他分別在國際上最著名的雜誌（如：Nature Medicine、Nature、J Clin Invest、Lancet、New England J Med, Science和J.Exp.Med）發表論文，被SCI收錄83篇。檢索其中的31篇在近五年來被引用1891次。影響因子高達293目前，張林琦教授多次被國際會議和國內大學邀請作學術報告和合作研究，是愛滋病領域年富力強的實力派科學家。
研究方向
愛滋病病毒的致病機理
愛滋病病毒與免疫系統的相互作用關係
抗愛滋病病毒疫苗和藥物的研發
抗愛滋病病毒抗體和淋巴細胞免疫反應的研究與套用
目前工作主要集中在加強中美雙方在HIV/AIDS領域的基礎與臨床研究合作。
代表文章
Sun, C., Z. Chen, X. Tang, Y. Zhang, L. Feng, Y. Du, L. Xiao, L. Liu, W. Zhu, L. Chen, and L. Zhang. 2013. Mucosal Prime with a Replicating Vaccinia-based Vaccine Elicits Protective Immunity against SIV Challenge in Rhesus Monkeys. J Virol in press.
Shang, H., J. Xu, X. Han, J. Spero Li, K. C. Arledge, and L. Zhang. 2012. HIV prevention: Bring safe sex to China.Nature 485:576-577.
Guo, D., X. Shi, K. C. Arledge, D. Song, L. Jiang, L. Fu, X. Gong, S. Zhang, X. Wang, and L. Zhang. 2012. A single residue within the V5 region of HIV-1 envelope facilitates viral escape from the broadly neutralizing monoclonal antibody VRC01. J Biol Chem.
Zuo, T., X. Shi, Z. Liu, L. Guo, Q. Zhao, T. Guan, X. Pan, N. Jia, W. Cao, B. Zhou, M. Goldin, and L. Zhang. 2011. Comprehensive analysis of pathogen-specific antibody response in vivo based on an antigen library displayed on surface of yeast. J Biol Chem 286:33511-33519.
Zhu, W., Y. Jiao, R. Lei, W. Hua, R. Wang, Y. Ji, Z. Liu, F. Wei, T. Zhang, X. Shi, H. Wu, andL. Zhang. 2011. Rapid turnover of 2-LTR HIV-1 DNA during early stage of highly active antiretroviral therapy.PLoS One 6:e21081.
Meng, S., Z. Liu, L. Xu, L. Li, S. Mei, L. Bao, W. Deng, R. Lei, L. Xie, C. Qin, and L. Zhang. 2011. Intranasal immunization with recombinant HA and mast cell activator C48/80 elicits protective immunity against 2009 pandemic H1N1 influenza in mice. PLoS One 6:e19863.
H Shang, X Han, X Shi, and L Zhang. Genetic and Neutralization Sensitivity of Diverse HIV-1 env Clones from Chronically Infected Patients in China. J Biol Chem. 2011 286,14531-14541.
Liu Z, Shan M, Li L, Lu L, Meng S, Chen C, He Y, Jiang S, L Zhang. In vitro selection and characterization of human immunodeficiency virus type 1 variants with increased resistance to sifuvirtide, a novel HIV-1 fusion inhibitor. J Biol Chem. 2010 1074, 10.
Lu, L., M. Jia, Y. Ma, L. Yang, Z. Chen, D.D. HO, Y. Jiang, and L. Zhang, The Changing face of HIV in China. Nature, 2008. 455: p. 607-609.
He, Y., Y. Xiao, H. Song, Q. Liang, D. Ju, X. Chen, H. Lu, W. Jing, S. Jiang, andL. Zhang, Design and evaluation of sifuvirtide: a novel HIV-1 fusion inhibitor. J Biol Chem, 2008.
Chen, H.Y., M. Di Mascio, A.S. Perelson, D.D. Ho, and L. Zhang, Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques. Proc Natl Acad Sci USA, 2007. 104(48): p. 19079-84.
Arron, S.T., R.M. Ribeiro, A. Gettie, R. Bohm, J. Blanchard, J. Yu, A.S. Perelson, D.D. Ho, and L. Zhang, Impact of thymectomy on the peripheral T cell pool in rhesus macaques before and after infection with simian immunodeficiency virus. Eur J Immunol, 2005. 35(1): p. 46-55.
Zhang, L., Z. Chen, Y. Cao, J. Yu, G. Li, W. Yu, N. Yin, S. Mei, L. Li, P. Balfe, T. He, L. Ba, F. Zhang, H.H. Lin, M.F. Yuen, C.L. Lai, and D.D. Ho, Molecular characterization of human immunodeficiency virus type 1 and hepatitis C virus in paid blood donors and injection drug users in china. J Virol, 2004. 78(24): p. 13591-9.
Zhang, L., C. Chung, B.S. Hu, T. He, Y. Guo, A.J. Kim, E. Skulsky, X. Jin, A. Hurley, B. Ramratnam, M. Markowitz, and D.D. Ho, Genetic characterization of rebounding HIV-1 after cessation of highly active antiretroviral therapy. J Clin Invest, 2000. 106(7): p. 839-45.
Zhang, L., B. Ramratnam, K. Tenner-Racz, Y. He, M. Vesanen, S. Lewin, A. Talal, P. Racz, A.S. Perelson, B.T. Korber, M. Markowitz, and D.D. Ho, Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med, 1999. 340(21): p. 1605-13.
Zhang, L., S.R. Lewin, M. Markowitz, H.H. Lin, E. Skulsky, R. Karanicolas, Y. He, X. Jin, S. Tuttleton, M. Vesanen, H. Spiegel, R. Kost, J. van Lunzen, H.J. Stellbrink, S. Wolinsky, W. Borkowsky, P. Palumbo, L.G. Kostrikis, and D.D. Ho, Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy. J Exp Med, 1999. 190(5): p. 725-32.
Zhang, L., T. He, Y. Huang, Z. Chen, Y. Guo, S. Wu, K.J. Kunstman, R.C. Brown, J.P. Phair, A.U. Neumann, D.D. Ho, and S.M. Wolinsky, Chemokine coreceptor usage by diverse primary isolates of human immunodeficiency virus type 1. J Virol, 1998. 72(11): p. 9307-12.
Zhang, L., Y. Huang, T. He, Y. Cao, and D.D. Ho, HIV-1 subtype and second-receptor use. Nature, 1996. 383(6603): p. 768.
Zhang, L., P. MacKenzie, A. Cleland, E.C. Holmes, A.J. Brown, and P. Simmonds, Selection for specific sequences in the external envelope protein of human immunodeficiency virus type 1 upon primary infection. J Virol, 1993. 67(6): p. 3345-56.
