As a Ph.D student in Toronto and Vienna, I trained as a molecular and cellular immunologist under the supervision of Dr. Josef Penninger, and then as a fellow at Harvard Medical School under the supervision of Dr. Vijay Kuchroo. My broad interest was on T cell-driven mechanisms of autoimmunity As a fellow, I refined this to focus on multiple sclerosis (MS), for which Canada has an extremely high rate of incidence. I studied the potential role of inhibitory “immune checkpoint” signaling in reducing T cell inflammation in mouse models of MS. My key contributions were 1st author papers in J Exp Med (2006; 268 cites as of October 2017) and Nat Med (2012; 107 cites). My publications as a trainee have been cited 859 times. In recognition of the importance of my work to the field of MS research in Canada, I was awarded the prestigious “EMD Serono Canada and endMS Network Transitional Career Development Award” ($500,000K; 2011-16).

As an independent researcher at Laval University(UL) since 2013, I have built a research program that focuses on the role of adaptive immunity to secondary progressive (SP) MS. There are several reasons for this. First, nearly 40% of MS patients develop SP disease, yet there are no available treatments for this form. Second, while the clinical evidence supporting a role for lymphocytes in SPMS is considerable, animal models that recapitulate their role are limited in number. As an FRQS Junior-1 scholar since 2014, I have created one of the few existing mouse models of T cell-driven SPMS. Intriguingly, mice in our model develop SP symptoms almost at the same frequency as human patients. This gives us the unique opportunity to dissect the molecular and cellular mechanisms that drive the pathogenesis of SPMS.

My independent research program has been supported by over $1.2 million in operating funds, in addition to a CFI award ($294K) and startup funds from the CHU de Québec, UL and FRQS (total $240K). The development of our unique model of SPMS was supported by an endMS Network Transitional Career Development Award (2013-16) and an MS Society of Canada (MSSOC) Operating Grant (2014-17). Ongoing funding in the lab includes: 1) a CIHR Catalyst Grant (2016-18); 2) MSSOC Operating Grant 2017-20); 3) NSERC Discovery Grant (2015-20).

Among other projects in the lab, we showed that interferon-beta, a first line drug for relapsing MS, directly represses the ability of T cells to cause MS-like disease in mice and causes them to express inhibitory “checkpoint” receptors (Boivin et al., PLOS ONE 2015). Furthermore, I led the first systematic analysis of cholesterol and its metabolites as biomarkers of MS progression (Zhornitsky et al., MS and Related Disorders). Our model of SPMS was the topic of a review (Doss et al., Front Immunol 2016).

Along with Nathalie Arbour (CHUM) I was the lead editor of a Front Immunol Special Topic and e-Book on the role of lymphocytes in CNS autoimmunity. I co-organize an annual CIHR-funded symposium on cytokine biology (CIACCO). I have served on multiple peer review committees including the MSSOC Personnel Awards Committee, FRQS doctoral awards committee FF5-11D, and starting in 2018, the MSSOC Biomedical Research Review Committee.

CHUL
2705, boulevard Laurier, T-2-50
Québec, Québec
Canada G1V 4G2

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18 entries « 1 of 4 »

Cronin SJF, Seehus C, Weidinger A, Talbot S, Reissig S, Seifert M, Pierson Y, McNeill E, Longhi MS, Turnes BL, Kreslavsky T, Kogler M, Hoffmann D, Ticevic M, da Luz Scheffer D, Tortola L, Cikes D, Jais A, Rangachari M, Rao S, Paolino M, Novatchkova M, Aichinger M, Barrett L, Latremoliere A, Wirnsberger G, Lametschwandtner G, Busslinger M, Zicha S, Latini A, Robson SC, Waisman A, Andrews N, Costigan M, Channon KM, Weiss G, Kozlov AV, Tebbe M, Johnsson K, Woolf CJ, Penninger JM

The metabolite BH4 controls T cell proliferation in autoimmunity and cancer.

Journal Article

Nature, 563 (7732), pp. 564-568, 2018, ISSN: 0028-0836.

Abstract | Links:

Pare A, Mailhot B, Levesque SA, Juzwik C, Ignatius Arokia Doss PM, Lecuyer MA, Prat A, Rangachari M, Fournier A, Lacroix S

IL-1β enables CNS access to CCR2hi monocytes and the generation of pathogenic cells through GM-CSF released by CNS endothelial cells.

Journal Article

Proc Natl Acad Sci U S A, 115 (6), pp. E1194-E1203, 2018, ISSN: 0027-8424.

Abstract | Links:

Cobos EJ, Nickerson CA, Gao F, Chandran V, Bravo-Caparros I, Gonzalez-Cano R, Riva P, Andrews NA, Latremoliere A, Seehus CR, Perazzoli G, Nieto FR, Joller N, Painter MW, Ma CHE, Omura T, Chesler EJ, Geschwind DH, Coppola G, Rangachari M, Woolf CJ, Costigan M

Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling.

Journal Article

Cell Rep, 22 (5), pp. 1301-1312, 2018.

Abstract | Links:

Rangachari M, Kerfoot SM, Arbour N, Alvarez JI

Editorial: Lymphocytes in MS and EAE: More Than Just a CD4+ World.

Journal Article

Front Immunol, 8 , pp. 133, 2017, ISSN: 1664-3224.

| Links:

Zhornitsky S, McKay KA, Metz LM, Teunissen CE, Rangachari M

Cholesterol and markers of cholesterol turnover in multiple sclerosis: relationship with disease outcomes.

Journal Article

Mult Scler Relat Disord, 5 , pp. 53-65, 2016, ISSN: 2211-0348.

Abstract | Links:

18 entries « 1 of 4 »

Active projects

  • Cellular and molecular mechanisms of inflammatory T cell regulation., Subvention, Conseil de recherches en sciences naturelles et génie Canada, Subventions à la découverte SD (individuelles et d'équipe), from 2015-04-01 to 2020-03-31
  • Centre hospitalier universitaire de Québec - CHU de Québec-Université Laval, Subvention, Centre hospitalier universitaire de Québec - Université Laval, Centres de recherche affiliés, from 2017-01-01 to 2099-12-31
  • Centre thématique de recherche en neurosciences, Subvention, Institutionnel - BDR, BDR - Centres de recherche reconnus, from 1999-06-01 to 2020-10-18
  • Investigating a novel inhibitory signaling mechanism that represses T cell-driven CNS autoimmunity, Subvention, Société canadienne de la sclérose en plaques, Subvention de fonctionnement, from 2017-04-01 to 2020-03-31

Recently finished projects

  • Elucidating the function of the immunoregulatory molecules Bat3 and Serpine1 in CD4+ and CD8+ T cell mediated CNS autoimmunity., Subvention, Société canadienne de la sclérose en plaques, Programme de subventions, from 2014-04-01 to 2017-03-31
  • Investigating sex-specific differences in a T cell-driven mouse model of MS., Subvention, Instituts de recherche en santé du Canada, Programme de subvention Catalyseur, from 2016-04-01 to 2018-03-31
  • Modulation de la réponse des lymphocytes T dans des modèles de la sclérose en plaques, Subvention, Fonds de recherche du Québec - Santé, Établissement de jeunes chercheurs - Juniors 1, from 2014-07-01 to 2017-06-30
  • Modulation de la réponse des lymphocytes T dans des modèles de la sclérose en plaques., Subvention, Fonds de recherche du Québec - Santé, Chercheur-boursier Juniors 1 et 2, Seniors, from 2014-07-01 to 2018-06-30
  • Role of the Tim-3 signaling pathway in modulating CNS autoimmunity., Subvention, Société canadienne de la sclérose en plaques, Programme de subventions, from 2013-05-01 to 2017-04-30
Data provided by the Université Laval research projects registery