BG 10 RM 7C103
10 CENTER DR
BETHESDA MD 20814
Dr. Nath received his MD degree from Christian Medical College in India in 1981 and completed a residency in Neurology from University of Texas Health Science Center in Houston, followed by a fellowship in Multiple Sclerosis and Neurovirology at the same institution and then a fellowship in Neuro-AIDS at NINDS. He held faculty positions at the University of Manitoba (1990-97) and the University of Kentucky (1997-02). In 2002, he joined Johns Hopkins University as Professor of Neurology and Director of the Division of Neuroimmunology and Neurological Infections. He joined NIH in 2011 as the Clinical Director of NINDS, the Director of the Translational Neuroscience Center and Chief of the Section of Infections of the Nervous System. His research focuses on understanding the pathophysiology of retroviral infections of the nervous system and the development of new diagnostic and therapeutic approaches for these diseases.
Neuropathogenesis of HIV infection : HIV reservoirs get established in the brain early during infection and current antiretroviral therapy does not impact the size of the reservoir. The brain also accumulates defective viral sequences, the role of which is poorly understood but is reminiscent of the endogenous retroviruses in the human genome. Our laboratory is focused on characterizing the virus in the brain and studying the mechanisms by which the virus persists for extended periods of time. We have shown that the HIV-Tat protein is produced in the brain despite adequate antiretroviral therapy, hence we are developing means to block its effects. We have established a well characterized cohort of HIV-infected individuals to determine the various forms of neurological manifestations and underlying disease pathophysiology. This cohort is also being used for early phase clinical trials to impact the viral reservoirs in the brain.
Role of endogenous retroviruses in neurological diseases : Retroviral sequences remain dormant in the human genome and occupy nearly 7-8% of the genomic sequence. We have shown that one of these viruses termed HERV-K (HML-2) is activated in patients with amyotrophic lateral sclerosis (ALS), and transgenic animals that express the envelope protein of HERV-K develop ALS like symptoms. Hence, we are now using a wide variety of in vitro, and in vivo studies to determine the physiological role of HERV-K in early stages of development and the mechanisms by which its expression is regulated and causes neurotoxicity to motor neurons. We are also developing new antiviral compounds and molecular techniques for blocking HERV-K.
Undiagnosed Neuroimmune and neuroinfectious diseases : Undiagnosed neuroinflammatory diseases carry a huge burden with devastating consequences. In collaboration with other researchers in NINDS and other institutes, we are investigating these patients and developing new diagnostic methods and modes of treatment for these diseases. An example of which is our observation that patients with Nodding syndrome have autoantibodies to a newly discovered protein in the brain, liemodin-1, caused by a molecular mimicry with a protein in a parasite, onchocerca. We have also discovered that under certain circumstances, RNA viruses such as Dengue can persist in the brain and present as a neurodegenerative disease.
Rachel Abrams, Ph.D.
Catherine DeMarino, Ph.D.
Marta Garcia Montojo, Ph.D.
Lisa Henderson, Ph.D.
Tony James, M.Sc
Barbara Jaruga, Ph.D.
Melina Jones, Ph.D.
Tory Johnson, Ph.D.
Darshan Pandya, M.D.
Myounghwa Lee, Ph.D.
Wenxue Li, Ph.D.
Cynthia McMahan, B.S.
Nicholas Pasternack, M.Sc
Kevon Sampson, M.Sc
Bryan Smith, M.D.
Amanda Wiebold, RN, BSN, CCRP
Niku Nouromohammadi, M.Sc.
Post baccalaureate Fellow
Devon Dietrich, B.Sc.
Post baccalaureate Fellow
- Ladifatou Fouanta, B.Sc.
Research Nurse Specialist
1) Li GH, Maric D, Major EO, Nath A (2020)
Productive HIV infection in astrocytes can be established via a non-classical mechanism
AIDS, 17-Feb, PMID:32073447
2) Wang T, Medynets M, Johnson KR, Douchet-O’Hare TT, DiSanza B, Li W, Xu Y, Bagnell A, Tyagi R, Sampson K, Malik N, Steiner J, Hadegan A, Kowalak J, O’Malley JO, Maric G, Nath A (2020)
Regulation of stem cell function and neuronal differentiation by HERV-K via mTOR pathway
Proc Natl Acad Sci, 13-Jul
3) Johnson TP, Larman HB, Lee M-H, Whitehead SS, Kowalak J, Toro C, Kim J, Faustin A, Pardo C, Kottapalli S, Howard J, Monaco D, Weisfeld-Adams J, Blackstone C, Galetta S, Snuderl M, Gahl WA, Kister I, Nath A (2019)
Chronic dengue virus encephalitis in a patient with progressive dementia
Annals of Neurology, Nov;86(5), 695-703
4) Cortese, I, Muranski P, Enose-Akahata Y, Ha SK, Smith B, Monaco MC, Ryschewitsch C, Major EO, Ohayon J, Schindler MK, Beck E, Reoma LB, Jacobson S, Reich DS, Nath A (2019)
Pembrolizumab Treatment of Progressive Multifocal Leukoencephalopathy
New England Journal of Medicine, 10-Apr-19, PMID:30969503
5) Henderson, LJ, Johnson TP, Smith B, Reoma LB, Santamaria UA, Bachani M, DeMarino C, Barclay RA, Sacktor N, McArthur JC, Letendre S, Steiner J, Kashanchi F, Nath A (2019)
Presence of Tat and Trans-activation response (TAR) element in spinal fluid despite antiretroviral therapy
AIDS, Dec 1;33, Suppl 2:S145-S157
6) Tory P. Johnson, Richa Tyagi, Paul R. Lee, Myoung-Hwa Lee, Kory R. Johnson, Jeffrey Kowalak, Abdel Elkahloun, Marie Medynets, Alina Hategan, Joseph Kubofcik, James Sejvar, Jeffrey Ratto, Sudhir Bunga, Issa Makumbi, Jane R. Aceng, Thomas B. Nutman, Scott F. Dowell and Avindra Nath (2017)
Nodding syndrome may be an autoimmune reaction to the parasitic worm Onchocerca volvulus
Science Translational Medicine 15 Feb 2017, Vol. 9, Issue 377, DOI: 10.1126/scitranslmed.aaf6953
7) Tyagi R, Li W, Bianchet MA, Nath A (2017)
Inhibition of human endogenous retrovirus-K by antiretroviral drugs
Retrovirology, Mar 22, 14(1), 10.1186/s12977-017-0347-4
8) Hategan A, Bianchet MA, Steiner J, Karnaukhova E, Masliah E, Fields A, Lee MH, Dickens AM, Haughey N, Dimitriadis EK, Nath A (2017)
HIV Tat protein and amyloid-β peptide form multifibrillar structures that cause neurotoxicity
Nat Struct Mol Biol, Apr;24(4), 379-386
9) Bowen LN, Tyagi R, Li W, Alfahad T, Smith B, Wright M, Singer EJ, Nath A (2016)
HIV-associated motor neuron disease: HERV-K activation and response to antiretroviral
Therapy Neurology, Oct 25;87(17):, 1756-1762
10) Li GH, Anderson C, Jaeger L, Do T, Major EO, Nath A (2015)
Cell-to-cell contact facilitates HIV transmission from lymphocytes to astrocytes via CXCR4
11) Nath A. (2015) Eradication of Human Immunodeficiency Virus from Brain Reservoirs
J. Neurovirology, 21, 227-234
12) Li W, Lee MH, Henderson L, Tyagi R, Bachani M, Steiner J, Campanac E, Hoffman DA, von Geldern G, Johnson K, Maric D, Morris HD, Lentz M, Pak K, Mammen A, Ostrow L, Rothstein J, Nath A (2015)
Human endogenous retrovirus-K contributes to motor neuron disease
Sci Transl Med, Sep 30;7(307), 307ra153
13) Uzasci L, Bianchet MA, Cotter R, Nath A (2014)
Identification of nitrated immunoglobulin variable regions in the HIV-Infected human brain: Implications in HIV Infection and Immune response
J Proteome Research 2014 Mar 7, 13(3), 1614-23
14) Johnson TP, Patel, K, Johnson K, Maric D, Calabresi, P, Hasbun R, Nath A (2013)
Induction of IL-17 and non-classical T-cell activation by HIV-Tat protein
Proc Natl Acad Sci, 110(33), 15388-93
15) Wang T, Choi E, Monaco MC, Campanac E, Medynets M, Do T, Rao P, Johnson KR, Elkahloun AG, Von Geldern G, Johnson T, Subramaniam S, Hoffman D, Major E, Nath A. (2013)
Derivation of Neural Stem Cells from Human Adult Peripheral CD34+ Cells for an Autologous Model of Neuroinflammation