Qingsheng Li

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Professor Biological Sciences qli4@unl.edu 402-472-5922 Morrison Center 305

Research Interests

My research is focused on studying HIV-1 pathogenesis, transmission and prevention using single cell in situ analyses and in vivo SIV-rhesus macaque and humanized-BLT (bone marrow liver and thymus) mouse models of HIV-1 infection. I have published extensively on HIV/SIV transmission, pathogenesis and prevention, including one paper in Science and two papers in Nature as the leading author.

Publication

2016

  • Yuan Z, Kang G, Ma F, Lu W, Fan W, Fennessey CM, Keele BF, Li Q. Recapitulating Cross-Species Transmission of SIVcpz to Humans Using Humanized-BLT Mice. J Virol. 2016 Jun 15. pii: JVI.00860-16. [Epub ahead of print]
  • Diego A. V., A. Demers, J.M. Shaw, G. Kang, D. Ball, I. Tuero, T. Musich, V. Mohanram, T. Demberg, T. S. Karpova, Q. Li, and M. Robert-Guroff. 2016. Vaccine Induction of Lymph Node–Resident Simian Immunodeficiency Virus Env-Specific T Follicular Helper Cells in Rhesus Macaques. J Immunol, 2016 Feb 15;196(4):1700-10.PMID: 26773147.
  • Sun M, Li Y, Yuan Z, Lu W, Kang G, Fan W, Li Q. VRC01 antibody protects against vaginal and rectal transmission of human immunodeficiency virus 1 in hu-BLT mice. Arch Virol. 2016 Sep;161(9):2449-55. doi: 10.1007/s00705-016-2942-4. Epub 2016 Jun 24.
  • Destache CJ, Mandal S, Yuan Z, Kang G, Date AA, Lu W, Shibata A, Pham R, Bruck P, Rezich M, Zhou Y, Vivekanandan R, Fletcher CV, Li Q. Topical Tenofovir Disoproxil Fumarate Nanoparticles Prevent HIV-1 Vaginal Transmission in a Humanized Mouse Model. Antimicrob Agents Chemother. 2016 May 23;60(6):3633-9. PMID: 27044548.
  • Zeng M, Smith AJ, Shang L, Wietgrefe SW, Voss JE, Carlis JV, Li Q, Piatak M Jr, Lifson JD, Johnson RP, Haase AT. Mucosal Humoral Immune Response to SIVmac239∆nef Vaccination and Vaginal Challenge. J Immunol. 2016 Mar 15;196 (6):2809-18. PMID: 26864031.
  • Abdulhaqq, SA., C. Zorrilla, G. Kang, X. Yin, V. Tamayo, KE. Seaton, J. Joseph, S. Garced, GD. Tomara, KA. Linn, AS. Foulkes, L Azzoni, M. VerMilyea, C. Coutifaris,  AV.  Kossenkov, LC. Showe, E. Kraiselburd, Q. Li, LJ. Montaner. HIV-1 Negative Female Sex Workers Sustain High Cervical IFNε, and Low Immune Activation and Expression of HIV-1 Required Host Genes, Mucosal Immunology. 2016 9(4):1027-38. doi: 10.1038/mi.

2015

  • Lu W, Demers AJ, Ma F, Kang G, Yuan Z, Wan Y, Li Y, Xu J, Lewis M, Li Q. Next-Generation mRNA Sequencing Reveals Pyroptosis-Induced CD4+ T Cell Death in Early Simian Immunodeficiency Virus-Infected Lymphoid Tissues. J Virol. 2015 Nov 11;90(2):1080-7. doi: 10.1128/JVI.02297-15. PMID: 26559826.
  • Li Q, Tso FY, Kang G, Lu W, Li Y, Fan W, Yuan Z, Destache CJ, Wood C. Early Initiation of Antiretroviral Therapy Can Functionally Control Productive HIV-1 Infection in Humanized-BLT Mice. J Acquir Immune Defic Syndr. 2015. 15; 69 (5):519-27. PMCID: 4503390.
  • Li Y, Kang G, Duan L, Lu W, Katze MG, Lewis MG, Haase AT, Li Q. SIV Infection of Lung Macrophages. PLoS One. 2015.10:e0125500.
  • Yukl SA, Shergill AK, Girling V, Li Q, Killian M, Epling L, Li P, Kaiser P, Haase A, Havlir DV, McQuaid K, Sinclair E, Wong JK. Site-specific differences in T cell frequencies and phenotypes in the blood and gut of HIV-uninfected and ART-treated HIV+ adults. PLoS One.  2015.10:e0121290.
  • Billingsley JM, Rajakumar PA, Connole MA, Salisch NC, Adnan S, Kuzmichev YV, Hong HS, Reeves RK, Kang HJ, Li W, Li Q, Haase AT, Johnson RP. Characterization of CD8+ T cell differentiation following SIV Delta nef vaccination by transcription factor expression profiling. PLoS Pathog 2015. 11:e1004740.
  • Haase AT, Rakasz E, Schultz-Darken N, Nephew K, Weisgrau KL, Reilly CS, Li Q, Southern PJ, Rothenberger M, Peterson ML, Schlievert PM. Glycerol Monolaurate Microbicide Protection against Repeat High-Dose SIV Vaginal Challenge. PLoS One 2015. 10:e0129465. 2014

2014

  • Demers, A., G. Kang, F. Ma, W. Lu, Z. Yuan, Y. Li, M. Lewis, E. N. Kraiselburd, L. Montaner, and Q. Li. The mucosal expression pattern of interferon-epsilon in rhesus macaques. J Leukocyte Biology, 2014. 96:1101-1107
  • Lu W, F. Ma, A. Tchourbanov, Y., Li, G. Kang, Z. Yuan, D. Wang, C. Zhang, J. Xu, M. Lewis, Q. Li. Virus-host mucosal interactions during early SIV rectal transmission. Virology, 2014. 464-465:406-414. PMID: 25128762
  • Wang, L. X., G. Kang, P. Kumar, W. Lu, Y. Li, Y. Zhou, Q. Li, and C. Wood. Humanized-BLT mouse  model of Kaposi's sarcoma-associated herpesvirus infection. Proc Natl Acad Sci U S A, 2014, 111:3146-51.  PMCID: PMC3939909   (Corresponding author).
  • Wang, N., Y. Li, W. Niu, M. Sun, R. Cerny, Q. Li, and J. Guo. Construction of a Live-Attenuated HIV-1 Vaccine through Genetic Code Expansion. Angewandte  Chemie  International. 2014, 5;53 (19):4867-71. PMID: 24715496  (Corresponding author) (Nat Chem commented this paper by  Lin, S., and P. R. Chen. Virus engineering: Fighting HIV at its own game. Nat Chem 2014 6:566-568)
  • Wang, Z., A. Zhang, Y. Wan, X. Liu, C. Qiu, X. Xi, Y. Ren, J. Wang, Y. Dong, M. Bao, L. Li, M. Zhou, S. Yuan, J. Sun, Z. Zhu, L. Chen, Q. Li, Z. Zhang, X. Zhang, S. Lu, P. C. Doherty, K. Kedzierska, and J. Xu. 2014. Early hypercytokinemia is associated with interferon-induced transmembrane protein-3 dysfunction and predictive of fatal H7N9 infection. Proc Natl Acad Sci U S A, 2014, 111:769-774.
  • Li, Q., M. Zeng, L. Duan, J. E. Voss, A. J. Smith, S. Pambuccian, L. Shang, S. Wietgrefe, P. J. Southern, C. S. Reilly, P. J. Skinner, M. L. Zupancic, J. V. Carlis, M. Piatak, D. Waterman, R. K. Reeves, K. Masek-Hammerman, C. A. Derdeyn, M. D. Alpert, D. T. Evans, H. Kohler, S. Müller, J. Robinson, J. D. Lifson, D. R. Burton, R. P. Johnson, and A. T. Haase. Live Simian Immunodeficiency Virus Vaccine Correlate of Protection: Local Antibody Production and Concentration on the Path of Virus Entry. The Journal of Immunology. 2014, 193:3113-3125. (cover article)
  • Shaheed A., M. Martinez, G. Kang, A. Foulkes, I. V. Rodriguez,  S.M. Nichols, M. Hunter, C. Sariol, L.A. Ruiz, B. Ross, X. Yin, D. Speicher, A. Haase, P.A. Marx, Q. Li, E. K., and L.J. Montaner. Serial Cervicovaginal Exposures with Replication-Deficient SIVsm Induce Higher Dendritic Cell (pDC) and CD4+ T-Cell Infiltrates Not Associated With Prevention but a More Severe SIVmac251 Infection of Rhesus Macaques. J. AIDS. 2014,  65:405-413 410. PMID: 24226059.
  • Smith, A. J., S. W. Wietgrefe, L. Shang, C. S. Reilly, P. J. Southern, K. E. Perkey, L. Duan, H. Kohler, S. Müller, J. Robinson, J. V. Carlis, Q. Li, R. P. Johnson, and A. T. Haase. Live Simian Immunodeficiency Virus Vaccine Correlate of Protection: Immune Complex–Inhibitory Fc Receptor Interactions That Reduce Target Cell Availability. The Journal of Immunology, 2014,  193:3126-3133.
  • Gibbs, A., T. Hirbod, Q. Li, K. Bohman, T. B. Ball, F. A. Plummer, R. Kaul, J. Kimani, K. Broliden, and A. Tjernlund.  Presence of CD8+ T Cells in the Ectocervical Mucosa Correlates with Genital Viral Shedding in HIV-Infected Women despite a Low Prevalence of HIV RNA-Expressing Cells in the Tissue. J Immunol 2014, 192:3947-57.
  • Massilamany, C., A. Gangaplara, T. Jia, C. Elowsky, Q. Li, Y. Zhou, and J. Reddy. In situ detection of autoreactive CD4 T cells in brain and heart using major histocompatibility complex class II dextramers. Journal of Visualized Experiments 2014 e51679.
  • Chandirasegaran M; A Gangaplara; T Jia; C Elowsky; G Kang; JJ Riethoven; Q Li; Y Zhou; J Reddy. Direct staining with major histocompatibility complex class II dextramers permits detection of antigen-specific, autoreactive CD4 T cells in situ. PloS One, 2014, 9:e87519.

Prior 2013

  • Patterson LJ, Kuate S, Daltabuit-Test M, Li Q, Xiao P, McKinnon K, Dipasquale J, Cristillo A, Venzon D, Haase A, Robert-Guroff M. Replicating Adenovirus-Simian Immunodeficiency Virus (SIV) Vectors Efficiently Prime SIV-Specific Systemic and Mucosal Immune Responses by Targeting Myeloid Dendritic Cells and Persisting in Rectal Macrophages, Regardless of Immunization Route. Clin Vaccine Immunol. 2012, 19(5):629-37. PMID:  22441384.
  • Reeves RK, TI Evans, J Gillis, FE Wong, G Kang, Q Li, and RP Johnson. SIV infection induces accumulation of plasmacytoid dendritic cells in the gut mucosa. J. Infect. Dis.  2012, 206(9):1462-8. PMID: 22711907.
  • Bokhari, S., R. Hegde, SM. Bokhari, R. Hegde, S. Callen, H. Yao, Adany, Q. Li, Z. Li, D. Pinson, H-W. Yeh, P. Cheney, and S. Buch . Morphine Potentiates Neuropathogenesis of SIV Infection in Rhesus Macaques. Journal of Neuroimmune Pharmacology. 2011, 6(4): 626–639, PMID 21431470.
  • Li Q, Wood C. Challenges and counter challenges in HIV/AIDS. Chin Med J (Engl). 2010 Dec;123(23):3379-80. PMID:22166517.
  • Smith A. J., Q. Li, S.W. Wietgrefe, et al. Host Genes Associated with HIV-1 Replication in Lymphatic Tissue. J. Immunol. 2010,185:5417-24.
  • García A, N.B. Siddappa, Q. Li, AT. Haase, K. Paul, F. Stroud, X. Zhang,  JA. Fountain, F. Villinger,  FJ. Novembre, JG. Else, WE. Secor, RM. Ruprecht.  AIDS and optic neuritis in a rhesus monkey infected with the R5 clade C SHIV-1157ipd3N4. J Med Primatol. 2010, 39:356–360, PMID- 20412378
  • Yukl, SA.l, S. Gianella,.E. Sinclair, L. Epling, Q. Li, et al. Differences in HIV Burden and Immune Activation within the Gut of HIV Positive Patients Receiving Suppressive Antiretroviral Therapy. J. Infect. Dis. 2010, 202:1553–1561.
  • Li, Q., J.D. Estes, P.M. Schlievert, et al. Glycerol monolaurate prevents mucosal SIV transmission. Nature 2009 458: 1034-1038. PMCID: PMC2785041
  • Li, Q., P.J. Skinner, S.-J. Ha, et al. Visualizing antigen-specific and infected cells in situ predicts outcomes in early viral infection. Science 2009 323: 1726-1729. PMCID: PMC2753492
  • Bosinger, SE., Q. Li, SN. Gordon, et al. Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys. J. Clin. Invest. 2009, 119:3556–3572. PMCID:PMC2786806.
  • Li, Q., A.J. Smith, T.W. Schacker, J.V. Carlis, L. Duan, C.S. Reilly, and A.T. Haase. Microarray analysis of lymphatic tissue reveals stage-specific, gene-expression signatures in HIV-1 infection. J. Immunol. 2009, 183: 1975–1982.
  • Li Q, J. Skinner P, Duan L, Haase AT. A technique to simultaneously visualize virus-specific CD8+ T Cells and Virus-Infected Cells In situ. J. Vis. Exp.2009 Aug 13;(30)
  • Li, Q., J.D. Estes, L. Duan, J. Jessurun, S. Pambuccian, C. Forster, S. Wietgrefe, M. Zupancic, T. Schacker, C. Reilly, J.V. Carlis, and A.T. Haase. Simian immunodeficiency virus-induced intestinal cell apoptosis is the underlying mechanism of the regenerative enteropathy of early infection. J. Infect. Dis.2008, 197:420-429.
  • Weiler, A.M., Q. Li, L. Duan, et al. Genital ulcers facilitate rapid viral entry and dissemination following intravaginal inoculation with cell-associated simian immunodeficiency virus SIVmac239. J. Virol. 2008, 82: 4154-4158. PMCID PMC2292998
  • Estes, J.D., Q. Li, M.R. Reynolds, et al. Premature induction of an immunosuppressive T regulatory response in acute SIV infection. J. Infect. Dis. 2006, 193:703-712.
  • Li, Q., L. Duan, J.D. Estes, et al. Peak SIV replication in “resting” memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature 2005, 434:1148-1152.
  • Miller, C.J., Q. Li, K. Abel, et al. Propagation and dissemination of infection after vaginal transmission of SIV. J. Virol. 2005, 79: 9217-9227
  • Li, Q., J.D. Lifson, L. Duan, et al. Potential roles for follicular dendritic cell associated osteopontin in lymphoid follicle pathology and repair and B cell regulation in HIV-1 and SIV infections. J. Infect. Dis. 2005, 192:1269-1276
  • Zhang, Z.-Q., S.W. Wietgrefe, Q. Li, et al. Roles of substrate availability and infection of resting and activated CD4+ T cells in transmission and acute simian immunodeficiency virus infection. Proc. Natl. Acad. Sci. U.S.A. 2004, 101:5640-5645.
  • Li, Q., K.G. Mansfield, A.A. Lackner, et al. Quantitative image analysis of simian immunodeficiency virus replication in macrophages co-infected with Mycobacterium avium complex. J. Infect. Dis. 2000, 181:867-871. Li, Q., K.G. Mansfield, A.A. Lackner, and A.T. Haase. Quantitative image analysis of simian immunodeficiency virus replication in macrophages co-infected with Mycobacterium avium complex. The Journal of Infectious Diseases. 2000, 181:867-871, PMID: 10720506.
  • Li Q, Eiden LE, Cavert W, Reinhart TA, Rausch DM, Murray EA, Weihe E, Haase AT. Increased expression of nitric oxide synthase and dendritic injury in simian immunodeficiency virus encephalitis. J Hum Virol.  1999, 2(3):139-45. PMID: 10413365.
  • Li, Q., K. Gebhard, T. Schacker, K. Henry, and A.T. Haase. The relationship between tumor necrosis factor and human immunodeficiency virus gene expression in lymphoid tissue. J. Virol.  1997, 71:7080-7082. PMID: 9261439, Citation 19.
  • Li Q., J. Guo and Q. Tao. Cloning and sequencing of HCV NS5 gene of a Chinese isolate. J. Beijing Med. Univ. 1997, 29:500-503. (Chi).
  • Li Q., J. Guo and Q. Tao. High level expressing in E. Coli of NS5 gene of hepatitis C virus in a non-infused form. Chi. J. Exp. Clin. Virol. 1996, 10:254-257. (Chi).
  • Li Q., J. Guo and Q. Tao. Amplify HCV-RNA by 'two-stage annealing temperature' RT-PCR. J. Chi. Biochem. 1996, 12:249-251. (Chi).
  • Li Q., and Q. Tao. Role of Hepatitis C Virus Envelope in HIV Vaccine. J. Chi. Preventive Med. 1995, 29:363-365. (Chi).
  • Li Q., and Q. Tao. Applications of Reverse Transcriptional Polymerase Chain Reaction in Hepatitis C Virus Research. J. Chi. Med. Lab. Sci. 1995, 18:57-59. (Chi).
  • Tao Q., Q. Li. Genetic Heterogeneity of Hepatitis C Virus and its Significances. J. Chi. Clin. Hepatol. 1994, 10:59-61. (Chi).

Active Federal and External Grants

  • R01 AI111862-01; J. Guo & Q.  Li (MPIs); 05/01/2014-04/31/2018; NIH, NIAID

Improve the Safety of an Efficacious Live-Attenuated Hiv-1 Vaccine through Unnatural Amino Acids Mediated Suppression of Blank Codon

The goal of this project is to investigate a novel strategy to allow live-attenuated HIV-1 (LAV) to replicate only in the presence of the three artificial regulatory elements that are not found in nature (novel Δnef-LAV) to improve the safety of conventional Δnef-LAV while still maintaining its efficacy against HIV-1 acquisition.

Role: PI

  • Martin Delaney Collaboratories for HIV Cure Research; L. Montaner, J. Riley (MPIs, Wistar Ins.); 07/01/16-06/30/2021; NIH, NIAID

The BEAT-HIV Delaney Collaboratory to Cure HIV

Test a hypothesis that through a better understanding of HIV latent reservoirs and reactivation, HIV functional cures will be achieved by combination immunotherapy inclusive of several arms of the immune response: innate, humoral and T cells.

Role: Co-I and subaward PI.

  • R01AI124804; J. Donald (PI, Univ. of Wyoming); 08/01/2016-07/31-2020; NIH, NIAID

Impact of Fc N-glycan structure on HIV-specific antibody functions

Role: Co-I and subaward PI.

  • 5 U19 AI096187-04; R. Ahmed, E. Hunter (MPIs, Emory Univ.); 07/01/2011-06/30/2016; NIH, NIAID

B-cell Biology of Mucosal Immune Protection from SIV Challenge

The goal of this project is to define, through advanced immunological and systems biology approaches, the underlying mechanisms for enhanced antibody avidity and protection.

Role: Co-I and subaward PI.

  • R01 AI117740-01; Destache, Christopher J (PI, Univ. of Creighton); 04/01/2015-03/31/2019; NIH, NIAID

Long-acting antiretroviral nanoparticles for HIV prophylaxis

The goal is to investigate the preclinical use of antiretroviral nanoparticles as a weekly prevention strategy.

Role: Other Professional and subaward PI.

  • R21/R33  1R21AI122377-01; Planelles, Vicente (PI, Univ. of Utah); 09/01/2015-08/31/2020; NIH, NIAID

Preclinical Development of Ingenol and HDACi Toward HIV Eradication

The existence of latent reservoirs of HIV-infected cells constitutes a major impediment towards viral eradication. This application seeks to characterize the mechanisms by which ingenol derivatives, with the help of HDAC inhibitors as adjuvants, induce viral reactivation from latency, with the ultimate goal of using this pathway as a target for viral eradication strategies.

Role:  Co-I and subaward PI.

  • R01; Shilpa Buch; (PI, UNMC, Nebraska); 04/01/2016-03/31/2021; NIH, NIDA

The combinatorial effects of Opiates and the emerging promoter-variant strains

We hypothesize that the 4-κB strains of clade C are more infectious leading to increased immune activation and increased end-organ pathogenesis.  Specifically, two aims are proposed: 1):  to assess the in vitro replication competence of SHIV clones containing 1, 2, 3 or 4 NF-κB binding sites in the promoter as well as env sequences of both clades B and C viruses, and 2) to assess the immune responses and disease pathogenesis in Indian rhesus macaques infected with the SHIV clones (clade B vs. C viruses - generated in SA1) in the absence or presence of opiate dependence; and to evaluate the influence of the NF-kB number (3 versus 4 NF-κB binding sites in the viral promoter) on viral latency in the presence of ART.

Role:  Co-I and subaward PI.

  • amfAR 109123-57-RGRL; Wood, Charles (PI); 01/01/2015-01/31/2017; The Foundation for AIDS Research

CNS as Reservoir for Subtype C HIV-1 Infection

Description: The response of potential HIV-1 subtype C tissue reservoirs to antiretroviral therapy (ART), especially in the brain of sub-Saharan infected subjects, is largely unknown. We will utilize archived and newly collected post- mortem brain and peripheral tissues that have been snap-frozen for nucleic acid analyses, or appropriately fixed and imbedded for immunohistochemistry, immunofluorescence and in situ hybridization to detect viral products and cell lineage markers.

Role: Co-I

Recent Completed Federal and External Grants:

  • R01 DK087625-01 (Li Q, PI); 08/15/2010-07/31/2015; NIH, NIDDK

The Early Events Determining SIV Rectal Transmission Anal intercourse is a common mode of HIV-1 transmission, particularly for men who have sex with men; however, many fundamental and mechanistic questions remain. The objective of this study is to understand the early events in HIV-1 rectal transmission and to gain new insights, which will potentially lead to new intervention strategies, including vaccines and topical microbicides optimized for rectal use.

Role: PI

  • 3 R01 DK087625-03S1 (Li Q, PI); 09/30/2011-07/31/2015; NIH, NIDDK

The Early Events of SIV Rectal Transmission in Indian and Chinese rhesus macaque

Role: PI

  • NIAID subcontract-N01-AI-30018 (Li, Q, PI); 10/01/2010-04/30/2011; NIH, NIAID

Transcriptome Study of SIV Rectal Transmission in Rhesus Macaques

Anorectum is a major HIV transmission route, especially for men who have sex with men. Study of the early events of rectal transmission of SIV in rhesus macaques of distinct origin will gain new insights into how to prevent HIV-1 rectal transmission, since HIV transmission occurs in individuals of distinct and diverse origin.

Role: PI

  • R01  R01AI084142 (Montaner, PI, Wistar Institute); 09/01/2010-08/31/2011; NIH, NIAID

Cellular Innate Activation as a Tactic to Prevent HIV-1 Transmission

Role: CO-I and subcontract PI.

  • CIHR OCH-134118; Francis Plummer (PI, University of Manitoba, Canada; 04/1/2014-4/30/2015; Canadian Institutes of Health Research (CIHR)

The Biology of FREM1 in HIV transmission

Study the FREM1 and its variants in resistance of susceptibility to vaginal HIV infection.

Role: Co-I and subaward PI

Book Chapters

  • Li Q.(2014). T cell based HIV-1 vaccine in the era of broadly neutralizing antibody (in Chinese). In Wang YC (Ed.) HIV Vaccine Development and Evaluation.
  • Li Q and C. Wood. (2014). Humanized-mouse versus non-human primate models of HIV-1 infection, In Poluektova LY, Cracia-Martinez JV., Koyanagi Y, Manz MG. and Tager AM (Ed.). Humanized Mice for HIV Research. Springer.
  • Li Q.(2014). Collagen Deposition and Fibrosis in the Lymphatic Tissues of HIV-1, in Thomas Hope, Douglas D. Richman, Mario Stevenson(Ed.). Encyclopedia of AIDS Encyclopedia of AIDS. Springer.
Specialization:
  • HIV Transmission, Vaccine, & Prevention
News:
Education:
  • Ph.D., Beijing Univeristy Medical School
  • Master Med. Sc., Shanxi Medical University
  • Medicine, Datong University Medicial School
  • M. SS, Univeristy of St. Thomas