Public Health Research Institute Center and
at the International Center for Public Health
New Jersey Medical School - Rutgers, The State University of New Jersey
225 Warren Street
Newark, New Jersey 07103, USA
Phone: (973) 854-3150
Fax: (973) 854-3201
Viral infection of the central nervous system (CNS) by viruses that attack the CNS, such as HIV, dengue, Japanese encephalitis, SARS and others, can result in neurologic dysfunction with devastating consequences in the infected individuals. The mechanisms that results in CNS invasion, inflammation and loss of neurons by these viruses are unknown. However, we hypothesize that blood brain barrier compromise, microglia/macrophage activation, secretion of inflammatory factors, and compromise of glial and neuronal survival/function are key features of these viral CNS infections.
Our current focus is in HIV, however, we will expand our scope of research to others viruses that invade the CNS and cause CNS compromise and death.
The main focuses of our research are:
1. The role of connexin and pannexin containing channels, gap junctions and hemichannels, in the pathogenesis of NeuroAIDS. Our studies demonstrated that these channels play a key role in the amplification of CNS damage from few HIV infected astrocytes to uninfected surrounding cells. We focus our research in the infection of glial cells and in the mechanisms of viral reactivation.
2. The role of pannexin-1 hemichannels, purinergic receptors and ATP in the HIV life cycle. Our studies demonstrated that these channels/receptors/neurotransmitters work together in human primary macrophages and CD4+ T lymphocytes to facilitate HIV infection and replication. Our major focus is to identify the different stages of the viral life cycle regulated by these channels/receptors/neurotransmitters.
3. To examine the role of tunneling nanotubes (TNT) in HIV spread and infection between immune cells. The major focus is to analyze the role of TNT during HIV infection and their role in cell to cell infection and inflammation.
4. The role of drugs of abuse in CNS communication and susceptibility to infections.
Our data indicated that drugs of abuse have profound effects on CNS communication, gap junctions and synaptic receptors, altering signaling coordination and neuronal/glial communication. In addition, drugs of abuse “weaken” key CNS structures such as the BBB, allowing pathogens to invade the brain more easily. Our laboratory is examining the cellular and molecular mechanism by which drugs of abuse enhances CNS invasion and compromise CNS function.
Experimental approach: We use cellular and molecular biological techniques to study the expression, post-transcriptional modifications and intercellular trafficking of neurotransmitters and their receptors, chemokines/cytokines as well as electrophysiology. Our approach involves the use of primary immune and CNS cells and tissues and samples obtained from individuals with NeuroAIDS.
The main goal of the Eugenin Lab is to discover how HIV is able to survive in the human body. In these videos, Associate Professor Eliseo Eugenin and his students describe their work with HIV as it presents itself in NeuroAids and in the cellular migration of HIV-infected T cells, as well as their related work with other, emerging pandemic viruses.
Doctoral student Paul Castellano studies HIV-infected cells of the central nervous system. In these cells, intrinsic apoptotic pathways are disrupted which leads to extended survival of infected cells that prolong infection and inflammation. Paul is targeting these disrupted pathways in order to eliminate HIV infection by allowing naturally occurring apoptosis to run its course.
Immune cells, including T cells, express a key membrane protein called Pannexin1 that forms a membrane channel. These channels regulate the release of intracellular messengers into the extracellular space, including ATP, PGEs, and ions. The Eugenin Lab previously demonstrated that the opening of these channels is essential for HIV infectivity and replication. Clearly, infectivity and replication are related to ethnicity, thus doctoral student Stephani Velasquez is examining the role of these channels in HIV replication and chemokine-mediated migration.
Valdebenito S, Barreto A, Eugenin EA (2018) The role of connexin and pannexin containing channels in the innate and acquired immune response. Biochim Biophys Acta 1860: 154-165. PMI: 28559189
Sarathy JP, Via LE, Weiner D, Blanc L, Boshoff H, Eugenin EA, Barry CE, 3rd, Dartois VA (2018) Extreme Drug Tolerance of Mycobacterium tuberculosis in Caseum. Antimicrob Agents Chemother 62. PMI: 29203492
Prevedel L, Morocho C, Bennett MVL, Eugenin EA (2017) HIV-Associated Cardiovascular Disease: Role of Connexin 43. Am J Pathol 187: 1960-1970. PMI: 28688235
Megra BW, Eugenin EA, Berman JW (2017) The Role of Shed PrP(c) in the Neuropathogenesis of HIV Infection. J Immunol 199: 224-232. PMI: 28533442
Malik S, Theis M, Eugenin EA (2017) Connexin43 Containing Gap Junction Channels Facilitate HIV Bystander Toxicity: Implications in NeuroHIV. Front Mol Neurosci 10: 404. PMI: 29259541
Malik S, Eugenin EA (2017) Role of Connexin and Pannexin containing channels in HIV infection and NeuroAIDS. Neurosci Lett. PMI: 28886986
Castellano P, Prevedel L, Eugenin EA (2017) HIV-infected macrophages and microglia that survive acute infection become viral reservoirs by a mechanism involving Bim. Sci Rep 7: 12866. PMI: 28993666
Calderon TM, Williams DW, Lopez L, Eugenin EA, Cheney L, Gaskill PJ, Veenstra M, Anastos K, Morgello S, Berman JW (2017) Dopamine Increases CD14(+)CD16(+) Monocyte Transmigration across the Blood Brain Barrier: Implications for Substance Abuse and HIV Neuropathogenesis. J Neuroimmune Pharmacol 12: 353-370. PMI: 28133717
Aslanyan L, Sanchez DA, Valdebenito S, Eugenin EA, Ramos RL, Martinez LR (2017) The Crucial Role of Biofilms in Cryptococcus neoformans Survival within Macrophages and Colonization of the Central Nervous System. J Fungi (Basel) 3. PMI: 29371529
Ariazi J, Benowitz A, De Biasi V, Den Boer ML, Cherqui S, Cui H, Douillet N, Eugenin EA, Favre D, Goodman S, Gousset K, Hanein D, Israel DI, Kimura S, Kirkpatrick RB, Kuhn N, Jeong C, Lou E, Mailliard R, Maio S, Okafo G, Osswald M, Pasquier J, Polak R, Pradel G, de Rooij B, Schaeffer P, Skeberdis VA, Smith IF, Tanveer A, Volkmann N, Wu Z, Zurzolo C (2017) Tunneling Nanotubes and Gap Junctions-Their Role in Long-Range Intercellular Communication during Development, Health, and Disease Conditions. Front Mol Neurosci 10: 333. PMI: 29089870
Velasquez S, Malik S, Lutz SE, Scemes E, Eugenin EA (2016) Pannexin1 Channels Are Required for Chemokine-Mediated Migration of CD4+ T Lymphocytes: Role in Inflammation and Experimental Autoimmune Encephalomyelitis. J Immunol 196: 4338-4347. PMI: 27076682
Shi L, Eugenin EA, Subbian S (2016) Immunometabolism in Tuberculosis. Front Immunol 7: 150. PMI: 27148269
Rao VR, Eugenin EA, Prasad VR (2016) Evaluating the Role of Viral Proteins in HIV-Mediated Neurotoxicity Using Primary Human Neuronal Cultures. Methods Mol Biol 1354: 367-376. PMI: 26714725
McFarren A, Lopez L, Williams DW, Veenstra M, Bryan RA, Goldsmith A, Morgenstern A, Bruchertseifer F, Zolla-Pazner S, Gorny MK, Eugenin EA, Berman JW, Dadachova E (2016) A fully human antibody to gp41 selectively eliminates HIV-infected cells that transmigrated across a model human blood brain barrier. AIDS 30: 563-572. PMI: 26595540
Marakalala MJ, Raju RM, Sharma K, Zhang YJ, Eugenin EA, Prideaux B, Daudelin IB, Chen PY, Booty MG, Kim JH, Eum SY, Via LE, Behar SM, Barry CE, 3rd, Mann M, Dartois V, Rubin EJ (2016) Inflammatory signaling in human tuberculosis granulomas is spatially organized. Nat Med 22: 531-538. PMI: 27043495
Malik S, Eugenin EA (2016) Mechanisms of HIV Neuropathogenesis: Role of Cellular Communication Systems. Curr HIV Res 14: 400-411. PMI: 27009098
Eugenin EA, Berman JW (2016) Improved Methods to Detect Low Levels of HIV Using Antibody-Based Technologies. Methods Mol Biol 1354: 265-279. PMI: 26714718
Castellano P, Nwagbo C, Martinez LR, Eugenin EA (2016) Methamphetamine compromises gap junctional communication in astrocytes and neurons. J Neurochem 137: 561-575. PMI: 26953131
Berman JW, Carvallo L, Buckner CM, Luers A, Prevedel L, Bennett MV, Eugenin EA (2016) HIV-tat alters Connexin43 expression and trafficking in human astrocytes: role in NeuroAIDS. J Neuroinflammation 13: 54. PMI: 26934876
Shi L, Salamon H, Eugenin EA, Pine R, Cooper A, Gennaro ML (2015) Infection with Mycobacterium tuberculosis induces the Warburg effect in mouse lungs. Sci Rep 5: 18176. PMI: 26658723
Doctoral Degree, Catholic University of Chile, Santiago, Chile, 2001.
Degree in Biochemistry, Universidad Austral de Chile, Chile, 1996.
Postdoctoral Studies, The Albert Einstein College of Medicine, Pathology, 2001-2004.
Instructor Scientific, The Albert Einstein College of Medicine, Pathology, 2005-2007.
Assistant Professor of Pathology, The Albert Einstein College of Medicine, Pathology, 2007-2012.