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Faculty

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Luis J. Montaner, DVM, DPhil

Wistar Institute Professor of Medicine
Full Member, Pathogenesis and Immunology/Vaccine Division, Penn Center for AIDS Research
Co-Director Viral/Primary Cell Core, Penn Center for AIDS Research
Co-Director, Faculty Mentoring Program, Developmental Core, Penn Center for AIDS Research
Faculty Mentor, Faculty Trans-partnership Development Program, Developmental Core, CFAR
Co-Chair, HIV Eradication and Functional Cure Scientific Working Group, Penn CFAR
Department: Medicine

Contact information
The Wistar Institute
3601 Spruce Street
Room 480
Philadelphia, PA 19104
Office: 215-898-3934
Fax: 215-573-9272
Lab: 215-898-3934
Graduate Group Affiliations
Education:
B.S.
Kansas State University, 1989.
M.Sc. (Veterinary Pathology)
Kansas State University, 1991.
D.V.M. (Veterinary Medicine)
Kansas State University, 1991.
D.Phil. (Experimental Pathology)
University of Oxford, 1995.
Post-Graduate Training
DVM/MSc Graduate Studentship, Department of Pathology, College of Veterinary Medicine, Kansas State University, 1989-1991.
Research Internships, New England Regional Primate Research Center, Harvard School of Medicine, 1990-1990.
Combined Post-doctoral Appointment and 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 new strategies of therapy that are better tolerated and more sustainable for patient populations than the life-long use of antiretroviral therapy.

Research Description
Introduction

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

Demers, A., Kang, G., Ma, F., Lu, W., Yuan, Z., Li, Y., Lewis, M., Kraiselburd, E.N., Montaner, L., Li, Q. : The Mucosal Expression Pattern of Interferon-ε in Rhesus Macaques. Journal of Leukocyte Biology August 2014.

Tomescu, C., Ross, B.N., Lynn, K., Mounzer, K.C., Kostman, J.R., Montaner, L.J. : A Correlate of HIV-1 Control Consisting of Both Innate and Adaptive Immune Parameters Best Predicts Viral Load by Multivariable Analysis in HIV-1 Infected Viremic Controllers and Chronically-Infected Non-Controllers. PLoS One July 2014.

Abdulhaqq, S., Martinez, M.I., Kang, G., Foulkes, A.S., Rodriguez, I.V., Nichols, S.M., Hunter, M., Sariol, C., Ruiz, L.A., Ross, B.N., Yin, X., Speicher, D.W., Haase, A., Marx, P.A., Li, Q., Kraiselburd, E., Montaner, L.J. : 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. Journal of Acquired Immune Deficiency Syndrome April 2014.

Dawany, N., Showe, L.C., Kossenkov, A.V., Chang, C., Ive, P., Conradie, F., Stevens, W.S., Sanne, I., Azzoni, L., Montaner, L.J. : Identification of a 251 Gene Expression Signature that Can Accurately Detect M. tuberculosis in Patients with and with HIV Co-infection. PLos One February 2014.

Stevenson, J.P., Kindler, H.L., Jacobs-Small, M., Hull, J., Schwed, D., Ranganathan, A., Papasavvas, E., Montaner, L.J., Sun, J., Heitjan, D.F., Langer, C.J., McPherson, J.M., Albelda, S.M. : Immunological effects of the TGFβ-blocking antibody GC1008 in malignant pleural mesothelioma patients. Oncoimmunology August 2013.

Chhatre, S., Metzger, D.S., Frank, I., Boyer, J., Thompson, E., Nidich, S., Montaner, L.J., Jayadevappa, R. : Effects of behavioral stress reduction Transcendental Meditation intervention in persons with HIV. AIDS Care February 2013.

Tebas, P. Stein, D., Binder-Scholl, G., Mukherjee, R., Brady, T., Rebello, T., Humeau, L., Papasavvas, E., Montaner, L.J., Schullery, D., Shaheen, F., Brennan, A.L., Zheng, Z., Cotte, J., Slepushkin, V., Veloso, E., Mackley, A., Hwang, W.T., Aberra, F., Zhan, J., Boyer, J., Collman, R.G., Bushman, F.D., Levine, B.L., June, C.H.: Antiviral effects of autologous CD4 T cells genetically modified with a conditionally replicating lentiviral vector expressing long anti-sense to HIV. Blood February 2013.

Mexas, A.M., Graf, E.H., Pace, M.J., Papasavvas, E., Azzoni, L., Busch, M.P., Di Mascio, M., Foulkes, A.S., Migueles, S.A., Montaner, L.J.: Concurrent Measures Of Total And Integrated HIV DNA Monitor Reservoirs And Ongoing Replication In Eradication Trials. AIDS November 2012.

Azzoni, L., Foulkes, A.S., Papasavvas, E., Mexas, A.M., Lynn, K.M., Mounzer, K., Tebas, P., Jacobson, J.M., Frank, I., Busch, M.P., Deeks, S.G., Carrington, M., O'Doherty, U., Kostman, J., Montaner, L.J. : Pegylated Interferon-α2A mono-therapy results in suppression of HIV-1 replication and decreased cell-associated HIV DNA integration. Journal of Infectious Diseases October 2012.

Tomescu, C., Duh, F-M, Hoh, R., Viviani, A., Harvill, K., Martin, M.P., Carrington, M., Deeks, S.G., Montaner, L.J.: Impact of Protective KIR/HLA Genotypes on NK Cell and T Cell Function in HIV-1 Infected Controllers. AIDS September 2012.

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Last updated: 09/16/2014
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