Primary Appointment:
 Neurology

GEBS Cluster Affiliations:
 IMV - Immunology, Microbiology, and Virology
 NS - Neuroscience
 TOX - Toxicology

University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 631
Rochester, New York 14642

Phone: (585) 273-1473
Fax: (585) 756-7665
E-Mail: harris_gelbard@urmc.rochester.edu

Effects of HIV-1 infection on neuronal function, signaling, and fate in the CNS

For the past several years my laboratory has focussed on the effects of chronic inflammation caused by human immunodeficiency virus type 1 (HIV-1) infection in the central nervous system (CNS). It is widely accepted that HIV-1 infection of the CNS may result in productive infection of brain-resident macrophages and microglia, and restricted infection (i.e. regulatory gene products expressed without production of progeny virus) of astrocytes, without direct cytolytic infection of neurons.

Gelbard HA. Synapses and Sisyphus: life without paraplegin. J Clin Invest. 113:185-7, 2004.

Latchney LR, Fallon MA, Culp DJ, Gelbard HA, Dewhurst S. Immunohistochemical Assessment of Fractalkine, Inflammatory Cells, and Human Herpesvirus 7 in Human Salivary Glands. J Histochem Cytochem. 52:671-682, 2004.

Dou H, Birusingh K, Faraci J, Gorantla S, Poluektova LY, Maggirwar SB, Dewhurst S, Gelbard HA, Gendelman HE. Neuroprotective activities of sodium valproate in a murine model of human immunodeficiency virus-1 encephalitis. J Neurosci. 23:9162-70, 2003.

Wang Z, Pekarskaya O, Bencheikh M, Chao W, Gelbard HA, Ghorpade A, Rothstein JD, Volsky DJ. Reduced expression of glutamate transporter EAAT2 and impaired glutamate transport in human primary astrocytes exposed to HIV-1 or gp120. Virology. 312:60-73, 2003.

Perry SW, Dewhurst S, Bellizzi MJ, Gelbard HA. Tumor necrosis factor-alpha in normal and diseased brain: Conflicting effects via intraneuronal receptor crosstalk? J Neurovirol. 8:611-24, 2002.

Ramirez SH, Sanchez JF, Dimitri CA, Gelbard HA, Dewhurst S, Maggirwar SB. Neurotrophins prevent HIV Tat-induced neuronal apoptosis via a nuclear factor-kappaB (NF-kappaB)-dependent mechanism. J Neurochem. 78:874-89, 2001.

Tong N, Sanchez JF, Maggirwar SB, Ramirez SH, Guo H, Dewhurst S, Gelbard HA. Activation of glycogen synthase kinase 3 beta (GSK-3beta) by platelet activating factor mediates migration and cell death in cerebellar granule neurons. Eur J Neurosci. 13:1913-22, 2001.

Zhu Y, Gelbard HA, Roshal M, Pursell S, Jamieson BD, Planelles V. Comparison of cell cycle arrest, transactivation, and apoptosis induced by the simian immunodeficiency virus SIVagm and human immunodeficiency virus type 1 vpr genes. J Virol. 75:3791-801., 2001.

Guo H, Tong N, Turner T, Epstein LG, McDermott MP, Kilgannon P, Gelbard HA. Release of the neuronal glycoprotein ICAM-5 in serum after hypoxic-ischemic injury. Ann Neurol. 48:590-602, 2000.

Maggirwar SB, Ramirez S, Tong N, Gelbard HA, Dewhurst S. Functional interplay between nuclear factor-kappaB and c-Jun integrated by coactivator p300 determines the survival of nerve growth factor-dependent PC12 cells. J Neurochem. 7:527-39, 2000.

Tong N, Perry SW, Zhang Q, James HJ, Guo H, Brooks A, Bal H, Kinnear SA, Fine S, Epstein LG, Dairaghi D, Schall TJ, Gendelman HE, Dewhurst S, Sharer LR, Gelbard HA. Neuronal fractalkine expression in HIV-1 encephalitis: roles for macrophage recruitment and neuroprotection in the central nervous system. J Immunol. 164:1333-9, 2000.

James HJ, Sharer LR, Zhang Q, Wang HG, Epstein LG, Reed JC, Gelbard HA. Expression of caspase-3 in brains from paediatric patients with HIV-1 encephalitis. Neuropathol Appl Neurobiol. 1999 Oct;25(5):380-6.

Zheng J, Thylin MR, Ghorpade A, Xiong H, Persidsky Y, Cotter R, Niemann D, Che M, Zeng YC, Gelbard HA, Shepard RB, Swartz JM, Gendelman HE. Intracellular CXCR4 signaling, neuronal apoptosis and neuropathogenic mechanisms of HIV-1-associated dementia. J Neuroimmunol. 98:185-200, 1999.

Maggirwar SB, Tong N, Ramirez S, Gelbard HA, Dewhurst S. HIV-1 Tat-mediated activation of glycogen synthase kinase-3beta contributes to Tat-mediated neurotoxicity. J Neurochem. 73:578-86, 1999.

Gelbard HA. Neuroprotective strategies for HIV-1-associated neurologic disease. Ann N Y Acad Sci. 890:312-3, 1999.

Fine SM, Maggirwar SB, Elliott PR, Epstein LG, Gelbard HA, Dewhurst S. Proteasome blockers inhibit TNF-alpha release by lipopolysaccharide stimulated macrophages and microglia: implications for HIV-1 dementia. J Neuroimmunol. 95:55-64, 1999.

Brooks AI, Chadwick CA, Gelbard HA, Cory-Slechta DA, Federoff HJ. Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res. 823:1-10, 1999.