MICHAEL C. LEVIN, M.D.

Fr-Professor
Neurology

Office: 422 LINK BUILDING
855 MONROE AVENUE
MEMPHIS TN 381630000
Tel: (901) 448-2243
mlevin@uthsc.edu

Curriculum Vitae

Research Description

     The long-term goals of my research are to determine how molecular mimicry contributes to neurodegeneration in autoimmune diseases of the central nervous system (CNS). Autoimmune diseases of the CNS such as multiple sclerosis (MS) cause disability and neurodegeneration correlates with disease progression. For almost 20 years, my laboratory has used a disease that mimics progressive MS: human T-lymphotropic virus type-1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/TSP), as a model for molecular mimicry. We’ve discovered that both MS and HAM/TSP patients make antibodies to heterogeneous ribonucleoprotein A1 (hnRNP A1), an RNA binding protein (RBP) over-expressed in neurons. Our data indicate that antibodies to hnRNP A1 result in neurodegeneration and changes in gene expression that correlate clinically with neural systems damaged in HAM/TSP and progressive forms of MS. Thus, we believe that we have discovered a link between autoimmunity and neurodegeneration. Recently, RBPs like hnRNP A1 have been shown to be major contributors to neuronal function and neurodegeneration in neurological diseases. The link between autoimmunity and neurodegeneration is an important one, and understanding its relationship may contribute to the discovery of novel mechanisms of neurodegeneration and therapies for progressive forms of MS, for which there are no effective treatments.

Research Interest/Specialty

Multiple Sclerosis

HTLV-1 associated neurologic diseases

Autoimmunity

Autoantibodies

Ribonuclear proteins

Research Keywords

HTLV-1

Molecular Mimicry

Multiple Sclerosis

hnRNP A1

Autoimmunity

Autoantibodies

Clinical Care Specialty/Interest

Michael C. Levin, M.D. is Chief, Neurology Service, Veterans Affairs Medical Center – Memphis and Professor of Neurology and Director, Multiple Sclerosis Center and Laboratory of Viral and Demyelinating Diseases, University of Tennessee Health Sciences Center.  Dr. Levin specializes in the care of people with multiple sclerosis and related diseases. He is recognized as one of the Best Doctors in America and is a fellow of the American Academy of Neurology and American Neurological Association. Dr. Levin has received over $2 million in federal and private funds to study the role of chronic viral infection in multiple sclerosis and related diseases.  He has received twenty awards for academic and scientific excellence including recognition by the National Multiple Sclerosis Society for the first ever phase III therapeutic trial in the Mid-south region.  Dr. Levin has over fifty peer-reviewed scientific presentations and publications including manuscripts published in some of the top journals in world including Nature Medicine, New England Journal of Medicine, Neurology, Annals of Neurology, Journal of Neurovirology and Neurology. His work has received special recognition by the American Academy of Neurology and the Society for Neuroscience. Dr. Levin was a post-doctoral fellow of the National Multiple Sclerosis Society at the Neuroimmunology Branch of the National Institutes of Health.  He did his neurology training at the New York Hospital/Cornell Medical Center – Memorial Sloan Kettering Cancer Center, in New York, where he was Chief Neurology Resident.  He received his medical degree at The Milton S. Hershey Medical Center of the Pennsylvania State University where he received 8 awards for academic and scientific excellence and performed additional research training at the Salk Institute.  He received his Bachelors in Science Degree in Chemistry with Special Honors, at The George Washington University.  Dr. Levin was recognized as outstanding volunteer by the Church Health Center, Memphis, TN, was selected as a “Healthcare Hero” finalist in 2006 by the Memphis Business Journal and received a “Golden Apple Teaching Award” at the University of Tennessee Health Sciences Center. 

Publications

  1. Sangmin Lee and Michael Levin. Novel somatic single nucleotide variants within the RNA binding protein hnRNP A1 in multiple sclerosis patients. F1000Research, 132 (3), 2014.
  2. Ganta, K, Malik, AM, Wood, JB, Levin, MC. Radial contrast enhancement on brain magnetic resonance imaging diagnostic of primary angiitis of the central nervous system: a case report and review of the literature. J Med Case Rep, 8, 26, 2013.
  3. Gardner, LA, Desiderio, DM, Groover, CJ, Hartzes, A, Yates, CR, Zucker-Levin, AR, Bloom, L, Levin, MC. LC-MS/MS identification of the one-carbon cycle metabolites in human plasma. Electrophoresis, 34 (11), 1710-6, 2013.
  4. Levin, MC, Lee, S, Gardner, LA, Shin, Y, Douglas, JN, Cooper, C. Autoantibodies to Non-myelin Antigens as Contributors to the Pathogenesis of Multiple Sclerosis. J Clin Cell Immunol, 4, 2013.
  5. Douglas, JN, Gardner, LA, Lee, S, Shin, Y, Groover, CJ, Levin, MC. Antibody transfection into neurons as a tool to study disease pathogenesis. J Vis Exp (67), 2012.
  6. Lee, S, Shin, Y, Clark, D, Gotuzzo, E, Levin, MC. Cross-reactive antibodies to target proteins are dependent upon oligomannose glycosylated epitopes in HTLV-1 associated neurological disease. J Clin Immunol, 32 (4), 736-45, 2012.
  7. Lee, S, Xu, L, Shin, Y, Gardner, L, Hartzes, A, Dohan, FC, Raine, C, Homayouni, R, Levin, MC. A potential link between autoimmunity and neurodegeneration in immune-mediated neurological disease. J Neuroimmunol, 235 (1-2), 56-69, 2011.
  8. Mainali, S, Afshani, M, Wood, JB, Levin, MC. The natural history of West Nile virus infection presenting with West Nile virus meningoencephalitis in a man with a prolonged illness: a case report. J Med Case Rep, 5, 204, 2010.
  9. Frohman Faan, EM, Beeravolu, LR, Frohman, TC, Remington, GM, Lee, S, Levin, MC, Daroff, RB, Dell'Osso, LF. "Not multiple sclerosis" and the changing face of HTLV-1: a case report of downbeat nystagmus. Neurology, 73 (21), 1812-3; author reply 1812-3, 2009.
  10. Beeravolu, LR, Frohman, EM, Frohman, TC, Remington, GM, Lee, S, Levin, MC. Pearls & Oy-sters: "Not multiple sclerosis" and the changing face of HTLV-1: A case report of downbeat nystagmus. Neurology, 72 (24), e119-20, 2009.
  11. Lee, S, Shin, Y, Marler, J, Levin, MC. Post-translational glycosylation of target proteins implicate molecular mimicry in the pathogenesis of HTLV-1 associated neurological disease. J Neuroimmunol, 2008.
  12. Lee, S, Levin, MC. Molecular mimicry in neurological disease: what is the evidence. Cell Mol Life Sci, 65 (7-8), 1161-75, 2008.
  13. Lee, SM, Dunnavant, FD, Jang, H, Zunt, J, Levin, MC. Autoantibodies that recognize functional domains of hnRNPA1 implicate molecular mimicry in the pathogenesis of neurological disease. Neurosci Lett, 401 (1-2), 188-93, 2006.
  14. Lee, SM, Morcos, Y, Jang, H, Stuart, JM, Levin, MC. HTLV-1 induced molecular mimicry in neurological disease. Curr Top Microbiol Immunol, 296, 125-36, 2005.
  15. Kalume, F, Lee, SM, Morcos, Y, Callaway, JC, Levin, MC. Molecular mimicry: cross-reactive antibodies from patients with immune-mediated neurologic disease inhibit neuronal firing. J Neurosci Res, 77 (1), 82-9, 2004.
  16. Morcos, Y, Lee, SM, Levin, MC. A role for hypertrophic astrocytes and astrocyte precursors in a case of rapidly progressive multiple sclerosis. Mult Scler, 9 (4), 332-41, 2003.
  17. Jernigan, M, Morcos, Y, Lee, SM, Dohan, FC, Raine, C, Levin, MC. IgG in brain correlates with clinicopathological damage in HTLV-1 associated neurologic disease. Neurology, 60 (8), 1320-7, 2003.
  18. Levin, MC, Lee, SM, Morcos, Y, Brady, J, Stuart, J. Cross-reactivity between immunodominant human T lymphotropic virus type I tax and neurons: implications for molecular mimicry. J Infect Dis, 186 (10), 1514-7, 2002.
  19. Levin, MC, Lee, SM, Kalume, F, Morcos, Y, Dohan, FC, Hasty, KA, Callaway, JC, Zunt, J, Desiderio, D, Stuart, JM. Autoimmunity due to molecular mimicry as a cause of neurological disease. Nat Med, 8 (5), 509-13, 2002.
  20. Khan, RB, Bertorini, TE, Levin, MC. HTLV-1 and its neurological complications. Neurologist, 7 (5), 271-8, 2001.
  21. Levin, MC, Rosenblum, MK, Fox, CH, Jacobson, S. Localization of retrovirus in the central nervous system of a patient co-infected with HTLV-1 and HIV with HAM/TSP and HIV-associated dementia. J Neurovirol, 7 (1), 61-5, 2001.
  22. Soldan, SS, Graf, MD, Waziri, A, Flerlage, AN, Robinson, SM, Kawanishi, T, Leist, TP, Lehky, TJ, Levin, MC, Jacobson, S. HTLV-I/II seroindeterminate Western blot reactivity in a cohort of patients with neurological disease. J Infect Dis, 180 (3), 685-94, 1999.
  23. Lehky, TJ, Levin, MC, Kubota, R, Bamford, RN, Flerlage, AN, Soldan, SS, Leist, TP, Xavier, A, White, JD, Brown, M, Fleisher, TA, Top, LE, Light, S, McFarland, HF, Waldmann, TA, Jacobson, S. Reduction in HTLV-I proviral load and spontaneous lymphoproliferation in HTLV-I-associated myelopathy/tropical spastic paraparesis patients treated with humanized anti-Tac. Ann Neurol, 44 (6), 942-7, 1998.
  24. Levin, MC, Krichavsky, M, Berk, J, Foley, S, Rosenfeld, M, Dalmau, J, Chang, G, Posner, JB, Jacobson, S. Neuronal molecular mimicry in immune-mediated neurologic disease. Ann Neurol, 44 (1), 87-98, 1998.
  25. Levin, MC, Jacobson, S. Cellular and humoral immune responses associated with HTLV-I associated myelopathy/tropical spastic paraparesis. Ann N Y Acad Sci, 835, 142-52, 1997.
  26. Levin, MC, Jacobson, S. HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP): a chronic progressive neurologic disease associated with immunologically mediated damage to the central nervous system. J Neurovirol, 3 (2), 126-40, 1997.
  27. Jacobson, S, Krichavsky, M, Flerlage, N, Levin, M. Immunopathogenesis of HTLV-I associated neurologic disease: massive latent HTLV-I infection in bone marrow of HAM/TSP patients. Leukemia, 11 Suppl 3, 73-5, 1997.
  28. Levin, MC, Lehky, TJ, Flerlage, AN, Katz, D, Kingma, DW, Jaffe, ES, Heiss, JD, Patronas, N, McFarland, HF, Jacobson, S. Immunologic analysis of a spinal cord-biopsy specimen from a patient with human T-cell lymphotropic virus type I-associated neurologic disease. N Engl J Med, 336 (12), 839-45, 1997.
  29. Walter, MJ, Lehky, TJ, Levin, MC, Fox, CH, Jacobson, S. Detection of HTLV-I in Peripheral Blood Lymphocytes from Patients with Chronic HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis and Asymptomatic Carriers by PCR-in situ Hybridization. J Biomed Sci, 4 (1), 54-60, 1997.
  30. Levin, MC, Krichavsky, M, Fox, RJ, Lehky, T, Jacobson, S, Fox, C, Kleghorn, F, White, J, Young, N, Edwards, RJ, Jack, NE, Bartholomew, C. Extensive latent retroviral infection in bone marrow of patients with HTLV-I-associated neurologic disease. Blood, 89 (1), 346-8, 1997.
  31. Fox, RJ, Levin, MC, Jacobson, S. Tumor necrosis factor alpha expression in the spinal cord of human T-cell lymphotrophic virus type I associated myelopathy/tropical spastic paraparesis patients. J Neurovirol, 2 (5), 323-9, 1996.
  32. Levin, MC, Fox, RJ, Lehky, T, Walter, M, Fox, CH, Flerlage, N, Bamford, R, Jacobson, S. PCR-in situ hybridization detection of human T-cell lymphotropic virus type 1 (HTLV-1) tax proviral DNA in peripheral blood lymphocytes of patients with HTLV-1-associated neurologic disease. J Virol, 70 (2), 924-33, 1996.
  33. Lehky, TJ, Fox, CH, Koenig, S, Levin, MC, Flerlage, N, Izumo, S, Sato, E, Raine, CS, Osame, M, Jacobson, S. Detection of human T-lymphotropic virus type I (HTLV-I) tax RNA in the central nervous system of HTLV-I-associated myelopathy/tropical spastic paraparesis patients by in situ hybridization. Ann Neurol, 37 (2), 167-75, 1995.