Public Health Research Institute Center and
at the International Center for Public Health
UMDNJ - New Jersey Medical School
225 Warren Street
Newark, New Jersey 07103, USA

Phone: (973) 854-3150
Fax: (973) 854-3201
e-mail: eugeniea@umdnj.edu



Research Summary

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.




Selected Publications


Bueno SM, Gonzalez PA, Cautivo KM, Mora JE, Leiva ED, Tobar HE, Fennelly GJ, Eugenin EA, Jacobs WR, Jr., Riedel CA, Kalergis AM (2008) Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG. Proc Natl Acad Sci U S A 105: 20822-20827. PMI: 19075247

Eugenin EA, Berman JW (2003) Chemokine-dependent mechanisms of leukocyte trafficking across a model of the blood-brain barrier. Methods 29: 351-361. PMI: 12725802

Eugenin EA, Branes MC, Berman JW, Saez JC (2003) TNF-alpha plus IFN-gamma induce connexin43 expression and formation of gap junctions between human monocytes/macrophages that enhance physiological responses. J Immunol 170: 1320-1328. PMI: 12538692

Eugenin EA, Clements JE, Zink MC, Berman JW (2011) Human immunodeficiency virus infection of human astrocytes disrupts blood-brain barrier integrity by a gap junction-dependent mechanism. J Neurosci 31: 9456-9465. PMI: 21715610

Eugenin EA, D'Aversa TG, Lopez L, Calderon TM, Berman JW (2003) MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis. J Neurochem 85: 1299-1311. PMI: 12753088

Eugenin EA, Eckardt D, Theis M, Willecke K, Bennett MV, Saez JC (2001) Microglia at brain stab wounds express connexin 43 and in vitro form functional gap junctions after treatment with interferon-gamma and tumor necrosis factor-alpha. Proc Natl Acad Sci U S A 98: 4190-4195. PMI: 11259646

Eugenin EA, Gamss R, Buckner C, Buono D, Klein RS, Schoenbaum EE, Calderon TM, Berman JW (2006) Shedding of PECAM-1 during HIV infection: a potential role for soluble PECAM-1 in the pathogenesis of NeuroAIDS. J Leukoc Biol 79: 444-452. PMI: 16507710

Eugenin EA, Gaskill PJ, Berman JW (2009) Tunneling nanotubes (TNT) are induced by HIV-infection of macrophages: a potential mechanism for intercellular HIV trafficking. Cell Immunol 254: 142-148. PMI: 18835599

Eugenin EA, Gonzalez H, Saez CG, Saez JC (1998) Gap junctional communication coordinates vasopressin-induced glycogenolysis in rat hepatocytes. Am J Physiol 274: G1109-1116. PMI: 9696712

Eugenin EA, King JE, Hazleton JE, Major EO, Bennett MV, Zukin RS, Berman JW (2011) Differences in NMDA receptor expression during human development determine the response of neurons to HIV-tat-mediated neurotoxicity. Neurotox Res 19: 138-148. PMI: 20094923

Eugenin EA, King JE, Nath A, Calderon TM, Zukin RS, Bennett MV, Berman JW (2007) HIV-tat induces formation of an LRP-PSD-95- NMDAR-nNOS complex that promotes apoptosis in neurons and astrocytes. Proc Natl Acad Sci U S A 104: 3438-3443. PMI: 17360663

Eugenin EA, Osiecki K, Lopez L, Goldstein H, Calderon TM, Berman JW (2006) CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS. J Neurosci 26: 1098-1106. PMI: 16436595

Hazleton JE, Berman JW, Eugenin EA (2010) Novel mechanisms of central nervous system damage in HIV infection. HIV AIDS (Auckl) 2: 39-49. PMI: 22096383






C.V.


Education

Doctoral Degree, Catholic University of Chile, Santiago, Chile, 2001.
Degree in Biochemistry, Universidad Austral de Chile, Chile, 1996.


Professional experience

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.