Penn Center for AIDS Research

Luis J. Montaner

faculty photo
Wistar Institute Professor of Medicine
Department: Medicine

Contact information
The Wistar Institute
3601 Spruce Street
Philadelphia, PA 19104
Office: 215-898-9143
Lab: 215-898-3934
Graduate Group Affiliations
Kansas State University, 1989.
D.V.M. (Veterinary Medicine)
Kansas State University, 1991.
M.Sc. (Veterinary Pathology)
Kansas State University, 1991.
D.Phil. (Experimental Pathology)
University of Oxford, 1995.
Post-Graduate Training
Assistant Electron Microscopist, Department of Veterinary Pathology, Kansas State University, 1986-1989.
Research Internships, New England Regional Primate Research Center, Harvard School of Medicine, 1990-1990.
DPhil Studentship, Sir William Dunn School of Pathology, University of Oxford, 1991-1994.
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Description of Research Expertise

Research Interests
Our goal is to develop a better understanding of HIV-1 immunopathogenesis and new immune-based strategies of anti-HIV therapy that are better tolerated and more sustainable for patient populations than the life-long use of antiretroviral therapy.

Research Description

The Montaner laboratory is investigating mechanisms of disease in HIV-1 infection and novel approaches to augment immune function by combining virological and immune-based research on patient-derived material as well as by using laboratory models of virus infection. The work is focused on 1) regulation of innate immunity, 2) identifying new mechanisms of immunodeficiency and discovering new approaches to reverse them, 3) exploring new therapy management practices, and 4) understanding the relationship between immune antiviral responses and control of HIV-1 infection.

Current Research Activities and Interests

Innate Immunity & HIV-1 Infection: Dendritic cells & Natural Killer Cells Direct or indirect interactions of viral particles with innate and specific adaptive immunity effector cells affects the cross talk between antigen presenting cells (APCs), NK cells and the antigen specific T and B-lymphocytes, and may contribute to regulate HIV disease progression. Specifically, we are pursuing analysis of the effects of HIV infection in macrophages, dendritic cells and Natural Killer cells.

A relationship between levels of HIV replication and innate cell function is supported by our preliminary data on DC and NK subset changes and viral replication in HIV-infected individuals showing an impairment of NK cell responses, APC endocytic uptake, differential expression of cell surface molecules associated with APC function, increased APC apoptosis, decreased IL-12 secretion, decreased IFN-? secretion and a loss of plasmacytoid dendritic cells (PDCs) and myeloid dendritic cells (MDCs) in PBMC. Based on these observations and the observed effects of antiretroviral therapy on DC and NK cell subsets, the inverse correlation between viral load and DC subsets in untreated HIV positive subjects and our observations of augmented NK lytic activity by activated DC, we are addressing longitudinal analysis and mechanistic experiments on DC/HIV interactions to test the hypothesis that HAART-mediated viral suppression restores mature NK and DC subsets necessary to activate innate mechanisms of antiviral control through lysis of infected cells. The long-term goal of this area of focus is to define the contribution of two major components of the innate immune system (accessory and Natural Killer cells) in controlling HIV replication thereby modifying disease progression. The short-term goal of our effort is to address the consequences of immune reconstitution on innate immunity following antiretroviral therapy, with particular emphasis on correlates of DC and NK cell functions and the consequences of HIV interactions with DC subsets. While adaptive HIV-specific immune responses continue to be an area of active investigation in AIDS research, the potential contribution of innate immune response, such as the relationship between DC subsets, disease progression and its consequences on other innate functions such as NK function remains largely unexplored in HAART settings. This study represents a hypothesis-driven collaborative effort by The Wistar Institute, the Infectious Disease Division of the University of Pennsylvania Hospital, Philadelphia FIGHT, Schering-Plough, Becton Dickinson, The Women's Interagency Study Cohort and the Multiple AIDS Cohort Study (MACS).

Selected Publications

Collora, J.A., Liu, R., Pinto-Santini, D., Pasalar, S., Ravindra, N., Ganoza, C., Lama, J.R., Alfaro, R., Chiarella, J., Spudich, S., Mounzer, K., Tebas, P., Montaner, L.J., van Dijk, D. Duerr, A., Ho, Y.-C: Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones. Immunity Jun 2022.

Invernizzi, L., Moyo, P., Cassel, J., Isaacs, F.J., Salvino, J.M., Montaner, L.J., Tietjen, I., Maharaj, V. : The use of hyphenated analytical techniques to identify the bioactive constituents of Gunnera perpensa L., a South African medicinal plant, which potently inhibit SARS-CoV-2 spike glycoprotein-host ACE2 binding. Annal. Bioanal. Chem. May 2022.

Dubé, K., Kanazawa, J., Roebuck, C., Johnson, S., Carter, W.B., Dee, L., Peterson, B., Lynn, K.M., Lalley-Chareczko, L., Hiserodt, E., Kim, S., Rosenbloom, D., Evans, B.R Anderson, M., Hazuda, D.J. Shipley, L., Bateman, K., Howell, B.J., Mounzer, K., Tebas, P., Montaner, L.J. : “We are looking at the future right now”: Community acceptability of a home-based viral load test device in the context of HIV cure-related research with analytical treatment interruptions in the United States. HIV Research & Clinical Practice Mar 2022.

Donthireddy, L., Vonteddu, P., Murthy, T., Kwak, T., Eraslan, R.-N., Podojil, J.R., Elhofy, A., Boyne, M.T.II., Puisis, J.J., Veglia, F., Sngh, S.S., Dotiwala, F., Montaner, L.J., Gabrilovich, D.I. : ONP-302 nanoparticles inhibit tumor growth by altering tumor-associated macrophages and cancer-associated fibroblasts. Journal of Cancer Mar 2022.

Dubé, K., Eskaf, S., Hastie, E., Agarwal, H., Henley, L., Roebuck, C., Carter, W.B., Dee, L., Taylor, J., Mapp, D., Campbell, D.M., Villa, T.J., Peterson, B., Lynn, K.M., Lalley-Chareczko, L., Hiserodt, E., Kim, S., Rosenbloom, D., Evans, B.R., Anderson, M., Hazuda, D.J., Shipley, L., Bateman, K., Howell, B.J., Mounzer, K., Tebas, P., Montaner, L.J: Preliminary acceptability of Home-Based Viral Load Testing in the Context of Analytical Treatment Interruptions in HIV Cure Trials: Results from a Nationwide Survey in the United States. Journal of Personalized Medicine Feb 2022.

Pederson, S., Collora, J., Kim, R., Yang, K., Razmi, A., Catalano, A., Yeh, Y.-H.J., Mounzer, K., Montaner, L., Ho, Y.-C. : Inhibition of a chromatin and transcription modulator SLTM increases HIV-1 reactivation identified by a CRISPRi screen. Journal of Virology In press 2022.

Jeong, M., Kudchokar S.B., Gil, A., Jeon, B., Park, G.H., Cho, Y., Lee H., Cheong, M.S., Kim, W., Hwang, Y.-H., Lee, J.-A., Lim, H., Kim, M.Y., Lallow, E., Brahmbhatt, T., Kania, S.A., Jhumur, N.C., Shan, J.W., Zahn, J.D., Shreiber, D.I., Singer, J., Lin, H., Spiegel, E.K., Pessaint, L., Porto, M., Van Ry, A., Nase, D., Kar, S., Andersen, H., Tietjen, I., Cassel, J., Salvino, J., Montaner, L.J., Park, Y.K., Muthumani, K., Roberts, C.C., Maslow, J. : Immune responses of a novel bi-cistronic SARS-CoV-2 DNA vaccine following intradermal immunization with section delivery. Frontiers in Virology In press 2022.

Tietjen, I., Cassel, J., Register, E., Zhou, X.Y., Messick, T.E., Keeney, F., Lu, L., Beattie, K.D., Rali, T., Ertl, H.C.J., Salvino, J.M., Davis, R.A., Montaner, L.J. : The natural stilbenoid -hopeaphenol inhibits cellular entry of SARS-CoV-2 WA1/2020, B.1.1.7 and B.1.351 variants. Antimicrobial Agents and Chemotherapy Nov 2021.

Cai, Y, Reddy Poli, A.N., Vadrevu, S., Gyampoh, K., Hart, C., Ross, B., Fair, M., Xue, F., Salvino, J.M., Montaner, L.J. : Reversible BCL6 BTB-specific Inhibitor Represses T Cell Activation, Tfh Cells Differentiation and Germinal Center Reaction in vivo. Eur J Imm July 2021.

Zhang, C., Lum, K.Y., Taki, A.C., Gasser, R.B., Byrne J.J., Wang, T., Blaskovich, M., Register, E.T., Montaner, L.J., Tietjen, I., Davis, R.A.: Design, synthesis, and screening of a drug discovery library based on an Eremophila-derived serrulatane scaffold. Phytochemistry 190: 112887, July 2021.

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Last updated: 06/21/2022
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