Wassim Elyaman, PhD
A growing body of evidence in experimental and human studies suggests the involvement of adaptive T cells in the pathogenesis of several neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Although peripheral lymphocyte infiltration is not a prominent feature in the AD, PD and ALS central nervous system (CNS) as in the autoimmune disease multiple sclerosis, T cell infiltration has been observed in the brains of these three neurodegenerative diseases. However, several questions regarding the involvement of adaptive immunity in neurodegenerative diseases remained unanswered.
The main line of research in Dr. Elyaman’s lab is to understand (1) how T cells are recruited to the CNS of neurodegenerative diseases, (2) what antigens are being presented to these T cells by CNS-resident innate immune cells, microglia, (3) how microglia-T cell axis regulates the disease pathogenesis, and lastly (4) what is the influence of genetic risk variants associated with these diseases on antigen-specific immune responses. To this end, the Elyaman’s group employ an array of genetic, molecular and biochemical approaches to identify novel molecular pathways and potentially druggable targets. All discoveries are made in the human system using patients’ blood, cerebrospinal fluid (CSF) cells, and fresh CNS autopsies that are analyzed at the single cell levels using RNA and T cell receptor sequencing. MHC peptidome of microglia is performed for the identification of potential self (auto-antigens) and non-self antigens (infectious agents) that are involved in priming the immune system. Key regulators of the immune response are further tested functionally using human microglia-neuron-T-cell tri-culture system as well as in vivo in animal models of neurodegenerative diseases.
- Assistant Professor of Neurological Sciences (in Neurology, the Taub Institute and the Institute for Genomic Medicine)
Credentials & Experience
Education & Training
- Maitrise, Molecular and Cell Biology, University of Limoges, France
- D.E.A. (Master), Toxicology, University of Rene Descartes, Paris, France
- PhD in Neuroscience, University of Limoges, France
- Fellowship: Brigham & Women's Hosp/Harvard Med
Honors & Awards
- 1998, PhD scholarship, EU
- 2008, Ruth L. Kirschstein National Research Service Award, NINDS
- 2012, National Multiple Sclerosis Society (NMSS), Pilot Award
- 2013, Massachusetts Neuroscience Consortium, Research Grant
- 2013, Harvard NeuroDiscovery Center, Pilot Award
- 2013, Whitaker Scholar, The Americas Committee for Treatment and Research in Multiple Sclerosis
- T cell lymphocytes
- Antigen-specific immune response in neurodegenerative diseases
- Infectious etiology of Alzheimer’s disease
- Modeling of microglia-T cell crosstalk
- Olah M, Menon V, Habib N, Taga MF, Ma Y, Yung CJ, Cimpean M, Khairallah A, Coronas-Samano G, Sankowski R, Grün D, Kroshilina AA, Dionne D, Sarkis RA, Cosgrove GR, Helgager J, Golden JA, Pennell PB, Prinz M, Vonsattel JPG, Teich AF, Schneider JA, Bennett DA, Regev A, Elyaman W, Bradshaw EM, De Jager PL. Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer's disease. Nat. Commun. 2020 Nov 30;11(1):6129.
- Ruan C, Sun L, Kroshilina A, Beckers L, De Jager P, Bradshaw EM, Hasson SA, Yang G, Elyaman W. A novel Tmem119-tdTomato reporter mouse model for studying microglia in the central nervous system. Brain Behav. Immun. 2020 Jan;83:180-191.
- Kaskow B, Buttrick T, Klein H-U, White C, Bourgeois J, Ferland R, Patsopoulos N, Bradshaw EM, De Jager PL, and Elyaman W. Multiple Sclerosis AHI1 Genetic Risk Promotes IFNg+ CD4+ T Cells. Neurol. Neuroimmunol. & Neuroinflamm. 2017.
- Ryan KJ, White CC, Patel K, Xu J, Olah M, Replogle JM, Frangieh M, Cimpean M, Winn P, McHenry A, Kaskow BJ, Chan G, Cuerdon N, Bennett DA, Boyd JD, Imitola J, Elyaman W, De Jager PL, Bradshaw EM. Context-specific effects of neurodegenerative disease variants in a model of human microglia. Sci. Transl. Med. 2017.
- Kurdi AT, Bassil R, Olah M, Wu C, Xiao S, Taga M, Frangieh M, Buttrick T, Orent W, Bradshaw EM, Khoury SJ, Elyaman W. Tiam1/Rac1 Complex Controls Il17a Transcription and Autoimmunity. Nat. Commun. 2016 Oct 11;7:13048.
- Orent W, McHenry AR, Rao DA, White C, Klein HU, Bassil R, Srivastava G, Replogle JM, Raj T, Frangieh M, Cimpean M, Cuerdon N, Chibnik L, Khoury SJ, Karlson EW, Brenner M, De Jager PL, Bradshaw EM* and Elyaman W. Rheumatoid Arthritis-Associated RBPJ Polymorphism Alters Memory CD4+ T Cells. Hum. Mol. Genet. 2016 Jan 15;25(2):404-17.
- Esposito F, Sorosina M, Ottoboni L, Lim ET, Replogle JM, Raj T, Brambilla P, Liberatore G, Guaschino C, Romeo M, Pertel T, Stankiewicz JM, Martinelli V, Rodegher M, Weiner HL, Brassat D, Benoist C, Patsopoulos NA, Comi G, Elyaman W, Martinelli Boneschi F, De Jager PL. SLC9A9 genotype influences response to interferon beta in MS patients: a pharmacogenetic study. Annal. Neurol. 2015