Center for Global Health Faculty

Director, Division of Neuroimmunology and Neurological Infections

Academic Degrees

Departmental Address

Contact Information

Email:

anath1+jhmi.edu

Phone:

443-287-4656

Fax:

410-502-8075

Link:

SciVal Experts Research Profile

Research and Professional Experience

Our laboratory is interested in studying the neuropathogenesis of HIV infection. Our goal is to understand the mechanisms by which HIV becomes latent in the brain and how HIv infected macrophages and glial cells lead to neuronal injury. For the last several years our laboratory has characterized a human in vitro brain model system to study HIV neuropathogenesis and identified that HIV proteins such as Tat and gp120 cause neuronal injury through interaction of cell surface receptors and induction of oxidative stress pathways. We have extended these observations to discover that there is a significant amount of oxidative stress in the CSF and brains of patients with HIV dementia. We are thus determining if this may serve as a surrogate marker of HIV dementia and could be used in developing countries where neuroimaging facilties and detailed neuropsychological evaluations cannot be easily performed. Further, we are interested in determining if host or viral genetics plays a role in mediating HIV dementia. In particular we are looking at genetic variations in the neurotoxic epitoes of HIV Tat protein in clades B and C and ApoE genes to determine if they may detmine neuronal susceptibility.

Keywords

HIV, brain, Tat, neuronal injury, dementia, gp120, oxidative stress

Honors and Awards

1985-1986 Chief Resident, Department of Neurology, University of Texas Health Science Center, Houston, Texas. 1986 Texas Neurological Society: For excellence in Neurological Research. 1988-1990 Scholarship, Fogarty International Center, N.I.H. Bethesda, Maryland. 1990-1993 Scholarship, Health Science Centre Research Foundation, Winnipeg, Manitoba. (1992-93 declined) 1992-1995 Scholarship and establishment grant, Manitoba Health Research Council (1993-95 declined) 1993-1998 Scholarship, National Health and Research Development Program (1997-98 declined) 1997-2002 Scientist Award, Medical Research Council of Canada, (declined) 1999. Faculty Research Award, University of Kentucky 1999. Clinical Clerkship Teaching Award, University of Kentucky 2001-2002 Endowed Professorship, University of Kentucky (2002-5 declined) 2002 Governor’s certificate of recognition for Science and Engineering award 2005-present: Federal Drug Adminstration (FDA), Member, Immunology advisory group 2006-present: Chair elect, Section of Neuroinfectious diseases, American Academy of Neurology 2006-present: National Institue of Drug Abuse, External Scientific AIDS Workgroup

Selected Publications

Peer Reviewed publications (2005-06) 1. Irani D, Anderson C, Gundry R, Cotter R, Moore S, Kerr, D, McArthur JC, Sacktor N, Pardo C, Jones, M, Calabresi P, Nath A*. Cleavage of Cystatin C in the CSF of patients with Multiple Sclerosis. Ann Neurol 59:237-247; 2006. 2. Patel J, Galey, D, Jones J, Ray P, Woodward J, Nath A, Mumper R. HIV-1 Tat-coated nanoparticles result in enhanced humoral immune responses and neutralizing antibodies compared to alum adjuvant. Vaccine 24:3564-3573: 2006. 3. Hahn K, Robinson, B, Anderson C, Li W, Gartner S, Simpson D, Morgello S, Nath A*. Differential effects of HIV infected macrophages on dorsal root ganglia neurons. Neurobiology of Disease (in revision) 4. Wang T, Allie R, Conant K, Haughey N, Turchan-Chelowo J, Hahn K, Rosen A, Steiner J, Keswani S, Jones M, Calabresi PA, Nath A* Granzyme B mediates neurotoxicity through a G-protein coupled receptor. FASEB J in press. 5. Shapshak P, Duncan R, Nath A, Turchan J, Kangueane P, Rodriguez H, Duran EM, Ziegler F, Amaro E, Lewis A, Rodriguez A, Minagar A, Davis W, Seth R, Elkomy FF, Chiappelli F, Kazic T. Gene Chromosomal Organization and Expression in Cultured Human Neurons Exposed to Cocaine and HIV-1 proteins gp120 and tat: Drug Abuse and NeuroAIDS. Frontiers in Bioscience 11, 1774-1793, May 1, 2006 6. Shapshak P, Duncan R, Turchan J, Nath A, Minagar A, Kangueane P, Davis W, Chiappelli F, Elkomy F, Seth R, Kazic T. Bioinformatics Models In Drug Abuse and Neuroaids: Using and Developing Databases, Bioinformation, 1 (3), 86-88, 2006. www.bioinformation.net 7. Wilson, ME, Allred, KF, Bisotti, AJ, Chauhan, A, Bruce-Keller, AJ, Nath, A. Estrogen suppresses Tat-induced transcription in glial cells. AIDS Research and Human Retroviruses, in press 8. Sui Y, Bittel L-S, Li S, Loganathan R, Pinson D, Dhillon N, Nath A, Kolson D, Narayan O, Buch S. CXCL10-induced Cell Death in Neurons: Role of Calcium Dysregulation. Eur J Neuroscience, in press. 9. Nath A*, Venkataramana A, Reich DS, Cortese I, Major EO. Progression of Progressive Multifocal Leukoencephalopathy despite treatment with beta-interferon. Neurology 66: 149-50; 2006. 10. Turchan-Cholewo J, Liu Y, Gartner S, Jie C, Peng X, Chu K, Chen C, Chauhan A, Haughey N, Cutler R, Mattson M, Pardo C, Conant K, Sacktor N, McArthur JC, Hauser KF, Gairola C, Nath A* Increased vulnerability of ApoE4 neurons to HIV proteins and opiates: protection by diosgenin and L-deprenyl. Neurobiology of Disease, In press 11. Caporello E, Nath A, Slevin J, Galey D, Steiner J, Hamilton G, Williams L, Haughey NJ. The Immunophilin Ligand GPI1046 Protects Neurons From the Lethal Effects of the HIV-1 Proteins gp120 and Tat by Modulating Endoplasmic Reticulum Calcium Load. Journal of Neurochemistry, In press 12. Riedel D, Ghate M, Nene M, Paranjape RS, Mehendale SM, Bollinger RC, Sacktor N, McArthur JC, Nath A*. Screening for HIV dementia in an HIV, clade C-infected population in India. J. Neurovirol In press 13. Robinson B, Turchan J, Anderson, C, Chauhan A, Nath A*. Modulation of HIV infection by anticonvulsant drugs. Journal of Neurovirology In press 14. Kendall, SL, Anderson CF, Nath A,Turchan-Cholewo J, Mactutus, CF, Booze RM. Gonadal steroids differentially modulate neurotoxicity of HIV and cocaine: testosterone and ICI 182,780 sensitive mechanism. BMC Neurosci 6:40-48, 2005 15. Clark JP 3rd, Sampair CS, Kofuji P, Nath A, Ding JM. HIV protein, transactivator of transcription, alters circadian rhythms through the light entrainment pathway. Am J Physiol Regul Integr Comp Physiol. 2005 Sep;289(3):R656-62. 16. Pocernich CB, Boyd-Kimball D, Poon HF, Thongboonkerd V, Lynn BC, Klein JB, Calebrese V, Nath A, Butterfield DA. Proteomics analysis of human astrocytes expressing the HIV protein Tat. Brain Res Mol Brain Res. 2005 Feb 18;133(2):307-16. 17. Pocernich CB, Fai Poon H, Boyd-Kimball D, Lynn BC, Nath A, Klein JB, Allan Butterfield D. Proteomic analysis of oxidatively modified proteins induced by the mitochondrial toxin 3-nitropropionic acid in human astrocytes expressing the HIV protein tat. Brain Res Mol Brain Res. 2005 Feb 18;133(2):299-306. 18. Banks WA, Robinson SM, Nath A. Permeability of the blood-brain barrier to HIV-1 Tat. Exp Neurol. 2005 May;193(1):218-27. 19. Williams MA, Turchan J, Lu Y, Nath A, Drachman DB. Protection of human cerebral neurons from neurodegenerative insults by gene delivery of soluble tumor necrosis factor p75 receptor. Exp Brain Res. 2005 Sep;165(3):383-91 20. Shankar SK, Mahadevan A, Satishchandra P, Kumar RU, Yasha TC, Santosh V, Chandramuki A, Ravi V, Nath A. Neuropathology of HIV/AIDS with an overview of the Indian scene. Indian J Med Res. 2005 Apr;121(4):468-88. 21. Helke KL, Queen SE, Tarwater PM, Turchan-Cholewo J, Nath A, Zink MC, Irani DN, Mankowski JL. 14-3-3 protein in CSF: an early predictor of SIV CNS disease. J Neuropathol Exp Neurol. 2005 Mar;64(3):202-8. 22. Zhang C, Gehlbach P, Gongora C, Cano M, Fariss R, Hose S, Nath A, Green WR, Goldberg MF, J. Zigler S, Jr, Sinha D A potential role for b- and g-crystallins in the vascular remodeling of the eye. Developmental Dynamics, 234:36-47; 2005. 23. Hollman AM, Christian DA, Ray PD, Galey D, Turchan J, Nath A, Bhattacharyya D. Selective Isolation and Purification of Tat Protein via Affinity Membrane Separation. Biotechnol Prog. 2005 Apr 1;21(2):451-459. 24. Flora G, Pu H, Lee YW, Ravikumar R, Nath A, Hennig B, Toborek M. Proinflammatory synergism of ethanol and HIV-1 Tat protein in brain tissue. Experimental Neurology, Volume 191, Issue 1, January 2005, Pages 2-12. 25. Andras IE, Pu H, Tian J, Deli MA, Nath A, Hennig B, Toborek M: Signaling mechanisms of HIV-1 Tat-induced alterations of claudin-5 expression in brain endothelial cells. J Cerebral Blood Flow and Metabolism. 2005 Mar 30 26. El-Hage N, Gurwell JA, Singh IN, Knapp PE, Nath A, Hauser KF. Synergistic increases in intracellular Ca(2+), and the release of MCP-1, RANTES, and IL-6 by astrocytes treated with opiates and HIV-1 Tat. Glia. Jan 2005 27. Hussain NS, Rumbaugh J, Kerr D, Nath A, Hillis SE. Effects of Prednisone and Plasma Exchange on Cognitive Impairment in Hashimoto’s Encephalopathy. Neurology 2005 Jan 11;64(1):165-6. Reviews/chapters/invited articles (2005-06) 1. Nath A. Brain abscess and parameningeal infections. Cecils textbook of Medicine 23rd edition 2. Nath A, Berger J. Poliomyelitis. Cecils textbook of Medicine 23rd edition 3. Nath A, Berger J. Rabies. Cecils textbook of Medicine 23rd edition 4. Nath A, Berger J. Encephalitis. Cecils textbook of Medicine 23rd edition 5. Berger J, Nath A. Neurological manifestations of HIV/AIDS. Cecils textbook of Medicine 23rd edition 6. Hauser KF, El-Hage N, Buch S, Nath A, Tyor WR, Bruce-Keller AJ, Knapp PE. Impact of opiate-HIV-1 interactions on Neuronal Signaling. Journal of Neuroimmune Pharmacology 1:1-9. 7. Wang T, Rumbaugh J, Nath A. Viruses and the brain: from inflammation to dementia. Clinical Science: Apr 1;110(4):393-407. 2006 8. Rumbaugh JA, Nath A.Developments in HIV neuropathogenesis. Current Pharmaceutical Design.12(9):1023-44. 2006 9. Rumbaugh J, Nath A. Substance Use Disorders and Neuro-AIDS in the HAART Era. In The Spectrum of Neuro-AIDS Disorders: Pathophysiology,Diagnosis and Treatment. ASM Press. Eds. K. Goodkin, P. Shapshak and A. Verma. 10. Nath A, Sacktor N. Influence of HAART on persistence of HIV in the central nervous system. Current Opinion in Neurology, In press. 11. Cortese I, Nath A. Case#11:A Young Woman With Ring-Enhancing Brain Lesions. Medscape General Medicine (ejournal) http://www.medscape.com/viewarticle/518245_5 Jan 17, 2006 12. Nath A, Hauser K, Prendergast M, Berger JR. Drug abuse and Neuro-AIDS. In Neuro-AIDS; Eds. Paul Shapshak, Alireza Minagar; Nova Science Publishers, Inc. 2005 13. Pocernich CB, Sultana R, Mohmmad-Abdul H, Nath A, Butterfield DA. HIV-dementia, Tat-induced oxidative stress, and antioxidant therapeutic considerations. Brain Res Rev. 50: 14-26; 2005 14. Kurt F. Hauser, Nazira El-Hage, Joseph R. Berger, William R. Tyor, Avindra Nath, Annadora J. Bruce-Keller and Pamela E. Knapp. Molecular Targets of Opiate Drug Abuse in NeuroAIDS Neurotoxicity Research, 2005, vol. 8(1-2). pp. 001-018 15. Mattson, M, Haughey N, Nath A. Cell death in HIV dementia. Cell Death and Differentiation. 2005 Aug;12 Suppl 1:893-904. 16. Li W, Galey D, Mattson MP, Nath A. Molecular and cellular mechanisms of neuronal cell death in HIV dementia. Neurotoxicity Research 2005; 8 (1,2) 1-16. 17. Nath A., Hersh L. Tat and amyloid: Multiple interactions (Editorial). AIDS 2005 Jan 28;19(2):203-4. 18. Rumbaugh J, Nath A. Approach to the Patient with a CSF Pleocytosis. In Cerebrospinal fluid in diseases of the nervous system. Ed:David Irani; Elsevier Press 19. McArthur J, Brew B, Nath A. Neurological complications of HIV infection. Lancet Neurology 4:543-55; 2005. (Science direct rating #3 amongst top 25 articles in Lancet Neurology (http://top25.sciencedirect.com/index.php?cat_id=5&subject_area_id=17&journal_id=14744422) 20. Wilson ME, Dimayuga FO, Reed JL, Curry TE, Anderson C, Nath A, Bruce-Keller AJ. Immune Modulation by Estrogens: Role in CNS HIV-1 Infection. Endocrinology (in Press)