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
29 entries « 1 of 3 »

Umair M, Fazazi MR, Rangachari M

Biological sex as a critical variable in CD4+ effector T cell function in preclinical models of multiple sclerosis.

Journal Article

Antioxid Redox Signal, 2021.

Abstract | Links:

Zhu C, Dixon KO, Newcomer K, Gu G, Xiao S, Zaghouani S, Schramm MA, Wang C, Zhang H, Goto K, Christian E, Rangachari M, Rosenblatt-Rosen O, Okada H, Mak T, Singer M, Regev A, Kuchroo V

Tim-3 adaptor protein Bat3 is a molecular checkpoint of T cell terminal differentiation and exhaustion.

Journal Article

Sci Adv, 7 (18), 2021.

Abstract | Links:

Doss PMIA, Umair M, Baillargeon J, Fazazi R, Fudge N, Akbar I, Yeola AP, Williams JB, Leclercq M, Joly-Beauparlant C, Beauchemin P, Ruda GF, Alpaugh M, Anderson AC, Brennan PE, Droit A, Lassmann H, Moore CS, Rangachari M

Male sex chromosomal complement exacerbates the pathogenicity of Th17 cells in a chronic model of central nervous system autoimmunity.

Journal Article

Cell Rep, 34 (10), 2021.

Abstract | Links:

Fani Maleki A, Cisbani G, Laflamme N, Prefontaine P, Plante MM, Baillargeon J, Rangachari M, Gosselin J, Rivest S

Correction to: Selective Immunomodulatory and Neuroprotective Effects of a NOD2 Receptor Agonist on Mouse Models of Multiple Sclerosis.

Journal Article

Neurotherapeutics, 18 (2), 2021.

| Links:

Fani Maleki A, Cisbani G, Laflamme N, Prefontaine P, Plante MM, Baillargeon J, Rangachari M, Gosselin J, Rivest S, Rivest S

Selective Immunomodulatory and Neuroprotective Effects of a NOD2 Receptor Agonist on Mouse Models of Multiple Sclerosis.

Journal Article

Neurotherapeutics, 18 (2), 2021.

Abstract | Links:

Pradeep Yeola A, Akbar I, Baillargeon J, Mercy Ignatius Arokia Doss P, Paavilainen VO, Rangachari M

Protein translocation and retro-translocation across the endoplasmic reticulum are crucial to inflammatory effector CD4 T cell function.

Journal Article

Cytokine, 129 , 2020.

Abstract | Links:

Yeola AP, Ignatius Arokia Doss PM, Baillargeon J, Akbar I, Mailhot B, Balood M, Talbot S, Anderson AC, Lacroix S, Rangachari M

Endogenous T Cell Receptor Rearrangement Represses Aggressive Central Nervous System Autoimmunity in a TcR-Transgenic Model on the Non-Obese Diabetic Background.

Journal Article

Front Immunol, 10 , 2019.

Abstract | Links:

St-Amour I, Bosoi CR, Pare I, Ignatius Arokia Doss PM, Rangachari M, Hebert SS, Bazin R, Calon F

Peripheral adaptive immunity of the triple transgenic mouse model of Alzheimer's disease.

Journal Article

J Neuroinflammation, 16 (1), 2019.

Abstract | Links:

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

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

Journal Article

Nature, 572 (7769), 2019.

Abstract | Links:

Crosson T, Roversi K, Balood M, Othman R, Ahmadi M, Wang JC, Tabatabaei M, Couture R, Eichwald T, Latini A, Prediger RD, Rangachari M, Seehus CR, Foster SL, Talbot S, Seadi Pereira PJ

Profiling of how nociceptor neurons detect danger - new and old foes.

Journal Article

J Intern Med, 286 (3), 2019.

Abstract | Links:

29 entries « 1 of 3 »
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Active projects

  • Cellular and molecular mechanisms of inflammatory T cell regulation., from 2015-04-01 to 2022-03-31
  • Cellular mechanisms regulating the pathogenesis of secondary progressive CNS autoimmunity, from 2018-10-01 to 2023-03-31
  • Élucidation des mécanismes immunitaires impliqués dans des maladies autoimmunitaires démyélisantes, from 2018-07-01 to 2022-06-30
  • Sex chromosomes dictate Th17 cell pathogenicity in a model of progressive CNS autoimmunity, from 2020-07-01 to 2023-06-30

Recently finished projects

  • Investigating a novel inhibitory signaling mechanism that represses T cell-driven CNS autoimmunity, from 2017-04-01 to 2020-03-31
  • The role of sex in regulating interleukin-17-mediated toxicity in the central nervous system, from 2018-04-01 to 2020-03-31
Data provided by the Université Laval research projects registery