From His Perspective

The rates of multiple sclerosis (MS), a debilitating neurological disease, are amongst the highest in the world in Canada.

In Saskatchewan, they may be even higher, where an estimated 3,500 to 3,700 people live with MS.

The U of S has recruited Dr. Michael Levin as the inaugural Chair in Multiple Sclerosis Clinical Research. Levin, who began his seven-year term in March 2017, will lead the research program focused on identifying causes of MS and developing new or improved treatments. 

“I’ve dedicated most of my adult life to exploring the causes of MS and the care of people with MS and I am grateful and humbled to be named the inaugural chair,” said Levin, a neurologist who was previously a professor in the College of Medicine at the University of Tennessee Health Science Center, and director of the Multiple Sclerosis Center and Laboratory of Viral and Demyelinating Diseases, in Memphis, Tenn. 

Levin, who has always been interested in neurosciences and completed his medical degree at Pennsylvania State University and a post-doctoral fellowship focused on multiple sclerosis at the National Institutes of Health in Bethesda, MD., said his interest in MS was sparked in the early ‘90s when “I met a couple of MS patients at the hospital, they were always strikingly young, intelligent and mid-career, so watching them become disabled was disturbing and at that time there were no FDA approved medications.”

Since then, his research has focused on the relationship between viruses, autoantibodies and acquired DNA mutations as potential causes of multiple sclerosis. 

At the U of S, Levin will lead a team of researchers, clinicians and students that includes Dr. Ilia Poliakov, Director of the MS Clinic, Dr. Katherine Knox, whose research focuses on MS and mobility, and Valerie Verge, director of the Cameco Neuroscience Research Centre, whose research focuses on nerve injury and repair mechanisms. Drs. Knox and Verge are U of S College of Medicine researchers.

“There really is a fair amount of infrastructure here already,” said Levin. “As a research chair, I think one of my major responsibilities is to get the pieces here to collaborate… We will make significant advances in MS by providing world-class care and cutting-edge research, garnering a national and international reputation for excellence.”

Biography

Michael C. Levin, MD, is the inaugural Saskatchewan Multiple Sclerosis Clinical Research Chair and Professor of Neurology and Anatomy, Physiology & Pharmacology at the University of Saskatchewan. He received his Bachelor of Science degree in Chemistry with special honors at George Washington University, his medical degree at Pennsylvania State University and basic neuroscience training at The Salk Institute with Drs. Max Cowan and Paul Sawchenko. Dr. Levin completed his residency training in Neurology at the New York Hospital/Cornell Medical Center – Memorial Sloan Kettering Cancer Center where Drs. Fred Plum and Jerry Posner mentored him including while he was chief neurology resident. He then completed his Multiple Sclerosis (MS) post-doctoral fellowship in the Neuroimmunology Branch at the National Institutes of Health with Drs. Henry McFarland and Steve Jacobson.

He was recruited to the University of Tennessee in Memphis where he moved up the ranks to professor with tenure, was Chief of the Neurology Service at the Memphis Veterans Affairs Medical Center and led the MS clinic and developed a translational research program based on the role that dysfunctional RNA binding proteins play in the pathogenesis of neurodegeneration in MS and relevant MS models. His work has been published in The New England Journal of Medicine, Nature Communications, Nature Medicine, Glia, Annals of Neurology, Neurology, the Journal of Comparative Neurology, and the Journal of Neuroscience Research. Dr. Levin has received more than 30 awards for academic excellence and his work has been recognized by the National Multiple Sclerosis Society, American Academy of Neurology, and the Society for Neuroscience.

Here at the University of Saskatchewan, Dr. Levin’s cutting-edge work on dysfunctional RNA binding proteins in MS has been recognized by a Canadian ‘Science, Technology, Innovation and Collaboration’ Award for the discovery of stress granules in brain tissue of an MS patient and a Canadian Tri-agency New Frontiers Research Grant – one of the most competitive in Canada - which is awarded for high risk, high reward interdisciplinary research that has the potential for significant impact. Most recently, his team discovered that an RNA binding protein named heterogeneous nuclear ribonuclear protein A1 (‘A1’ for short), is abnormal in nerve cells of people with MS. Abnormal A1 causes nerve cell death resulting in permanent disability. Using innovative drug design, Dr. Levin’ team identified multiple drugs that normalized A1 in nerve cells, which not only stopped nerve cells from dying, but also promoted their regeneration! These new drugs, which are being patented and prepared for clinical trials, are designed to prevent disability and improve the lives of persons living with MS. 

Dr. Levin is married to his lovely wife of more than 30 years, Dr. Audrey Zucker-Levin, an academic physical therapist. He has two strappingly handsome sons and is an avid sailor and scuba diver.

Recent Publications

  • Salapa, H.E., Thibault, P.A., Libner, C.D., Ding, Y., Clarke, J.P., Denomy, C., Hutchinson, C., Abidullah, H.M., Hammond, S.A., Pastushok, L., Vizeacoumar, F.S. & Levin, M.C. (2024). hnRNP A1 dysfunction alters RNA splicing and drives neurodegeneration in multiple sclerosis (MS). Nature Communications, 15: 356. https://rdcu.be/dvqwA

  • Vizeacoumar, F., Vizeacoumar, F. & Levin, M.C. (Submitted). Genome-wide screens reveal lack of (telomeric repeat containing RNA) TERRA methylation as a vulnerable target for telomerase overexpressing cancers. Nature.

  • Clarke, J.P., Thibault, P.A., Fatima, S., Salapa, H.E., Kalyaanamoorthy, S., Aravindhan, G. & Levin, M.C. (2023). Sequence- and structural-specific RNA oligonucleotide binding attenuates heterogeneous nuclear ribonucleoprotein A1 dysfunction. Frontiers in Molecular Biosciences, 10:1178439. doi: 10.3389/fmolb.2023.1178439. PMID: 37426420; PMCID: PMC10325567.

  • Tokarska, N., Johnston, J., Salapa, H.E., Levin, M.C., Popescu, B., Muir, G. & Verge, V. (2023). Acute intermittent hypoxia: a novel non-invasive therapy that promotes intrinsic repair in the EAE model of MS. Glia, 71(8): 2045-2066. doi: 10.1002/glia.24381.

  • Jahanbazi Jahan-Abad, A., Salapa, H.E., Libner, C.D., Thibault, P.A. & Levin, M.C. (2022). hnRNP A1 dysfunction in oligodendrocytes contributes to the pathogenesis of multiple sclerosis (MS). Glia, 71(3): 633-647.

  • Libner, C.D., Salapa, H.E., Hutchinson, C, Stang, T., Hammond, A. & Levin, M.C. (2022). Autoimmunity to a ribonucleoprotein drives neuron loss in an in vivo model of multiple sclerosis. Neurobiology of Disease, 140: 105775.

  • Anees, A., Salapa, H.E., Thibault, P.A., Hutchinson, C., Hammond, A.S. & Levin, M.C. (2021). Knockdown of heterogeneous nuclear ribonucleoprotein A1 results in neurite damage, altered stress granule biology and cellular toxicity in differentiated neuronal cells. eNeuro, 8(6): 00350-21.2021.

  • Clarke, J.P., Thibault, P.A., Salapa, H.E., Kim, D.E., Hutchinson, C. & Levin, M.C. (2021). Multiple sclerosis associated hnRNP A1 mutations alter hnRNP A1 dynamics and influence stress granule formation. International Journal of Molecular Sciences, 22(6): 2909.

  • Saini, A., Cochran, C., Zucker-Levin, A., Donkers, S.J., Kumar, P., Knox, K.B., MacPherson, J., Salapa, H.E. & Levin, M.C. (2021). A tripartite knowledge translation program: innovative patient-centered approach to clinical research participation for individuals with multiple sclerosis. Multiple Sclerosis International, 2021: 7.

  • Kahovec, C., Saini, A. & Levin, M.C. (2021). Diagnostic Dilemma: An atypical case of astrocytoma in a patient with relapsing remitting multiple sclerosis. Neurology International, 13(2): 240-251.

  • Saini, A., Zucker-Levin, A., McMillan, B., Kumar, P., Donkers, S.J. & Levin, M.C. (2021). A descriptive correlational study to evaluate three measures of assessing upper extremity function in individuals with multiple sclerosis. Multiple Sclerosis International, 2021: 8.

  • Clarke, J.P., Salapa, H.E., Thibault, P.A. & Levin, M.C. (2021). A comprehensive analysis of the role of hnRNP A1 function and dysfunction in the pathogenesis of neurodegenerative disease. Frontiers in Molecular Biosciences, 8: 659610.

  • Thibault, P.A., Ganesan, R., Kalyaanamoorthy, S., Clarke, J.P., Salapa, H.E. & Levin, M.C. (2021). hnRNP A/B proteins: an encyclopedic assessment of their roles in homeostasis and disease. Biology, 10(8): 712.

  • Li, M., Hamilton, R., Salapa, H.E. & Levin, M.C. (2021). Proinflammatory cytokines and autoantibodies induce dysfunctional RNA binding protein biology in mouse primary cortical neurons. Brain Sciences, 11: 1282.

  • Libner, C.D., Salapa, H.E. & Levin, M.C. (2020). The potential contribution of dysfunctional RNA binding proteins to the pathogenesis of neurodegeneration in multiple sclerosis and relevant models. International Journal of Molecular Sciences, 21(13): 4571; https://doi.org/10.3390/ijms21134571

  • Saini, A., Bach, K., Poliakov, I., Knox, K. & Levin, M.C. (2020). MRI spinal cord lesions in a cohort of multiple sclerosis patients in Saskatchewan, Canada. International Journal of MS Care https://doi.org/10.7224/1537-2073.2019-081

  • Salapa, H.E., Libner, C.D. & Levin, M.C. (2020). Dysfunctional RNA binding protein biology and neurodegeneration in EAE in female mice. Journal of Neuroscience Research doi:10.1002/jnr.24554.

  • Libner, C., Salapa, H.E. & Levin, M.C. (2020). Antibodies to the RNA binding protein heterogeneous nuclear ribonucleoprotein A1 contribute to neuronal loss in an animal model of multiple sclerosis. Journal of Comparative Neurology doi: 0.1002/cne.24845

  • Martindale-Adams, J., Zuber, J., Levin, M.C., Burns, R., Graney, M.J. & Nichols, L.O. (2020). Integrating caregiver support into multiple sclerosis care. Multiple Sclerosis International https://doi.org/10.1155/2020/3436726

  • Freedman MS, Devonshire V, Duquette P, Giacomini PS, Giuliani F, Levin MC, Montalban X, Morrow SA, Oh J, Rotstein D, Yeh EA, Canadian MS Working Group (2020) Treatment Optimization in Multiple Sclerosis: Canadian MS Working Group Recommendations. Can J Neurol Sci.47(4):437-455. PMID: 32654681

  • Salapa HE, Hutchinson C, Popescu BF, Levin MC (2020). Neuronal RNA-binding protein dysfunction in multiple sclerosis cortex. Ann Clin Transl Neurol. 7(7):1214-1224. PMCID:PMC7359129

  • Libner CD, Salapa HE, Levin MC. (2020) The Potential Contribution of Dysfunctional RNA-Binding Proteins to the Pathogenesis of Neurodegeneration in Multiple Sclerosis and Relevant Models. Int J Mol Sci. 2020;21(13):E4571. PMCID: PMC7369711

  • Knox, KB, Saini, A, Levin, MC (2020) The Dilemma of When to Stop Disease-Modifying Therapy in Multiple Sclerosis: A Narrative Review and Canadian Regional Reimbursement Policies. International Journal of MS Care Vol. 22,2 (2020): 75-85. PMCID: PMC7204360

  • Lee, S., Salapa, HE, Levin, MC (2019). Localization of near-infrared labeled antibodies to the central nervous system in experimental autoimmune encephalomyelitis. PLoS ONE. 14(2): 1-10. PMCID: PMC6377130

  • Salapa, H, Johnson, C, Hutchinson, C, Popescu, B, Levin, MC (2018). Dysfunctional RNA binding proteins and stress granules in Multiple Sclerosis. Journal of Neuroimmunology. 324: 149-156. PMID: 30190085

  • Levin, MC & Kahovec C (2019) Stabilization without rituximab following disease activation in an alemtuzumab treated multiple sclerosis patient and overview of the literature. International Journal of MS Care Vol. 21,3 (2019):125-128. PMCID: PMC6552997

  • Levin MC, Lee S, Gardner LA, Shin Y, Douglas JN, Salapa HE. (2017). Autoantibodies to heterogeneous nuclear ribonuclear protein A1 (hnRNPA1) cause altered 'ribostasis' and neurodegeneration; the legacy of HAM/TSP as a model of progressive multiple sclerosis. J Neuroimmunol. 304: 56-62. PMID: 27449854

  • Salapa HE, Lee S, Shin Y and Levin MC. (2017). Contribution of the degeneration of the neuroaxonal unit to the pathogenesis of multiple sclerosis. Brain Sciences. 7(6): 69. PMCID: PMC5483642

  • Douglas JN, Gardner LA, Salapa HE, Lalor SJ, Lee S, Segal BM, Sawchenko PE, Levin MC. (2016). Antibodies to the RNA binding protein hnRNP A1 contribute to neurodegeneration in a model of central nervous system autoimmune inflammatory disease. J Neuroinflammation. 13(1): 178. PMCID: PMC4938923

  • Douglas JN, Gardner LA, Salapa HE, Levin MC. (2016). Antibodies to the RNA binding protein heterogeneous nuclear ribonucleoprotein A1 colocalize to stress granules resulting in altered RNA and protein levels in a model of neurodegeneration in Multiple Sclerosis. J Clin Cell Immunol. 7(2): 402. PMCID: PMC4928374

  • Tang J, Bailey J, Chang C, Faris R, Hong SH, Levin MC, Wang J. (2016). Effects of specialty pharmacy care on health outcomes in multiple sclerosis. American Health Drug Benefits. 9(8): 420-29. PMCID: PMC5394553

  • Gardner LA, Levin, MC. (2015). Importance of Apolipoprotein A-I in Multiple Sclerosis. Front Pharmacol. 6: 278. PMCID: PMC4654019

  • Levin MC, Jackson WC. (2014). Developing a therapeutic plan for treating MS: evidence for new treatments. J Clin Psychiatry. 75(12): e34. PMID: 25551246

  • Ganta K, Malik A, Wood JB, Levin MC. (2014). Radial contrast enhancement on brain magnetic imaging diagnostic of primary angiitis of the central nervous system: case report and review of the literature. (Editor’s Featured article) . J of Medical Case Reports. 8(26): 1-5. PMCID: PMC3917527

  • Meyers L, Groover CJ, Douglas J, Lee S, Levin MC, Gardner LG. (2014). A role for Apolipoprotein A-I in the pathogenesis of multiple sclerosis. Journal of Neuroimmunology. 277(1-2): 176-85. PMID: 25468275

  • Levin MC, Douglas JN, Meyers L, Lee S, Shin Y, Gardner LA.(2014). Neurodegeneration in multiple sclerosis involves multiple pathogenic mechanisms. Degenerative Neurological and Neuromuscular Disease. 4: 49-63. PMCID: PMC7337253

  • Lee S, Levin MC. (2014). Novel somatic single nucleotide variants within the RNA binding protein hnRNP A1 in multiple sclerosis patients. (Editor’s featured article). F1000Research. 3(132): 1-19. PMCID: PMC4168748

  • Levin MC, Lee S, Gardner LA, Shin Y, Douglas JN, Cooper C. (2013). Autoantibodies to non-myelin antigens as contributors to the pathogenesis of multiple sclerosis. J Clin Cell Immunol. 4: 148. PMCID: PMC3866957

  • Douglas JN, Gardner L, Levin MC. (2013). Antibodies to an intracellular antigen penetrate neuronal cells and cause deleterious effects. J Clinical & Cellular Immunology. 4(1): 134. 

  • Gardner LA, Desiderio DM, Groover CJ, Yates CR, Zucker-Levin AR, Bloom L, Levin MC. (2013). LC-MS/ MS Identification of the one carbon cycle metabolites in human plasma.Electrophoresis. 34: 1710-1716. PMID: 23417555

  • Levin MC, Lee S, Gardner L, Shin Y, Douglas J, Groover C. (2012). Pathogenic mechanisms of neurodegeneration based on the phenotypic expression of progressive forms of immune-mediated neurologic disease. Degenerative Neurological and Neuromuscular Disease. 2: 175-187. PMCID: PMC6065584

  • Lee S, Shin Y, Clark D, Gotuzzo E, Levin MC. (2012). Cross-reactive antibodies to target proteins are dependent upon oligomannose glycosylated epitopes in HTLV-1 associated neurological disease. Journal of Clinical Immunology. 32: 736-745. PMID: 22392044

  • Douglas J, Gardner L, Lee S, Shin Y, Groover C, Levin MC. (2012). Antibody transfection into neurons as a tool to study disease pathogenesis. Journal of Visualized Experiments. 7(67): e4154. PMID: PMC3490253