Description of Research Expertise:
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.
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).
Uzzan M, Tokuyama M, Rosenstein AK, Tomescu C, SahBandar IN, Ko HM, Leyre L, Chokola A, Kaplan-Lewis E, Rodriguez G, Seki A, Corley MJ, Aberg J, La Porte A, Park E-Y, Ueno H, Oikonomou I, Doron I, Iliev ID, Chen BK, Lui J, Schacker TW, Furtado GC, Lira SA, Colombel J-F, Horowitz A, Lim JK, Chomont N, Rahman AH, Montaner LJ, Ndhlovu LC, Mehandru S: Anti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1-infected individuals Sci Transl Med 10 (461): pii:eaau4711,2018.
Bertagnolli LN, White JA, Simonetti FR, Beg SA, Lai J, Tomescu C, Murray AJ, Antar AAR, Zhang H, Margolick JB, Hoh R, Deeks SG, Tebas P, Montaner LJ, Siliciano RF, Laird GM, Siliciano JD: The role of CD32 during HIV-1 infection Nature 561 (7723): E17-E19,2018.
Vadrevu, S., Trbojevic-Akmacic, I., Kossenkov, A.V., Colomb, F., Giron, L., Anzurez, A., Lynn, K., Mounzer, K., Landay, A.L., Kaplan, R.C., Papasavvas, E., Montaner, L.J., Lauc, G., Abdel-Mohsen, M.*: Plasma and immunoglobulin G galactosylation associated with HIV persistence during antiretroviral therapy J Leukoc Biol 104 (3): 461-471,2018.
Vadrevu SK, Trbojevic-Akmacic I, Kossenkov AV, Colomb F, Giron LB, Anzurez A, Lynn K, Mounzer K, Landay AL, Kaplan RC, Papasavvas E, Montaner LJ, Lauc G, Abdel-Mohsen M: Frontline Science: Plasma and immunoglobulin G galactosylation associate with HIV persistence during antiretroviral therapy J Leukoc Biol 104 (3): 461-471,2018.
Lada SM, Huang K, VanBelzen DJ, Montaner LJ, O'Doherty U, Richman DD: Quantitation of Integrated HIV Provirus by Pulsed-Field Gel Electrophoresis and Droplet Digital PCR J Clin Microbiol : pii: JCM.01158-18,2018.
Papasavvas E, Lada SM, Joseph J, Yin X, Liu Q, Azzoni L, Mounzer K, Kostman JR, Richman D, Montaner LJ: Analytical antiretroviral therapy interruption does not irreversibly change preinterruption levels of cellular HIV AIDS 32 (13): 1763-1772,2018.
Davis RW IV, Papasavvas E, Klampatsa A, Putt M, Montaner LJ, Culligan MJ, McNulty S, Friedberg JS, Simone CB II, Singhal S, Albelda SM, Cengel KA, Busch TM: A Preclinical Model to Investigate the Role of Surgically-Induced Inflammation in Tumor Responses to Intraoperative Photodynamic Therapy Lasers Surg Med 50 (5): 440-450,2018.
Papasavvas E, Lada SM, Joseph J, Yin X, Liu Q, Azzoni L, Mounzer K, Kostman JR, Richman D, Montaner LJ: Analytical ART interruption does not irreversibly change pre-interruption levels of cellular HIV AIDS 32 (13): 1763-1772,2018.
Abdel-Mohsen M, Kuri-Cervantes L, Grau-Exposito J, Spivak AM, Nell RA, Tomescu C, Vadrevu S, Serra-Peinado C, Genesca M, Castellvi J, Wu G, Del Rio Estrada PM, González-Navarro M, Lynn K, King CT, Vemula S, Cox K, Mounzer K, Kostman J, Frank I, Paiardini M, Hazuda D, Reyes-Terán G, Howell B, Tebas P, Martinez-Picado J, Planelles V, Buzon MJ, Betts MR, Montaner LJ: CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells Sci Transl Med 10 (437): pii: eaar6759,2018.
Chitre AS, Kattah MG, Rosli YY, Pao M, Deswal M, Deeks SG, Hunt PW, Abdel-Mohsen M, Montaner LJ, Kim CC, Ma A, Somsouk M, McCune JM: A20 upregulation during treated HIV disease is associated with intestinal epithelial cell recovery and function PLoS pathogens 14 (3): e1006806,2018.
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