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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24 entries « 2 of 3 »

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:

Zhu C, Sakuishi K, Xiao S, Sun Z, Zaghouani S, Gu G, Wang C, Tan DJ, Wu C, Rangachari M, Pertel T, Jin HT, Ahmed R, Anderson AC, Kuchroo VK

Corrigendum: An IL-27/NFIL3 signalling axis drives Tim-3 and IL-10 expression and T-cell dysfunction.

Journal Article

Nat Commun, 6 , pp. 7657, 2015, ISSN: 2041-1723.

| Links:

Zhu C, Sakuishi K, Xiao S, Sun Z, Zaghouani S, Gu G, Wang C, Tan DJ, Wu C, Rangachari M, Pertel T, Jin HT, Ahmed R, Anderson AC, Kuchroo VK

An IL-27/NFIL3 signalling axis drives Tim-3 and IL-10 expression and T-cell dysfunction.

Journal Article

Nat Commun, 6 , pp. 6072, 2015, ISSN: 2041-1723.

Abstract | Links:

Boivin N, Baillargeon J, Doss PM, Roy AP, Rangachari M

Interferon-β suppresses murine Th1 cell function in the absence of antigen-presenting cells.

Journal Article

PLoS ONE, 10 (4), pp. e0124802, 2015.

Abstract | Links:

Ignatius Arokia Doss PM, Roy AP, Wang A, Anderson AC, Rangachari M

The Non-Obese Diabetic Mouse Strain as a Model to Study CD8(+) T Cell Function in Relapsing and Progressive Multiple Sclerosis.

Journal Article

Front Immunol, 6 , pp. 541, 2015, ISSN: 1664-3224.

Abstract | Links:

Rangachari M, Kuchroo VK

Using EAE to better understand principles of immune function and autoimmune pathology.

Journal Article

J Autoimmun, 45 , pp. 31-9, 2013, ISSN: 0896-8411.

Abstract | Links:

Wu C, Pot C, Apetoh L, Thalhamer T, Zhu B, Murugaiyan G, Xiao S, Lee Y, Rangachari M, Yosef N, Kuchroo VK

Metallothioneins negatively regulate IL-27-induced type 1 regulatory T-cell differentiation.

Journal Article

Proc Natl Acad Sci U S A, 110 (19), pp. 7802-7, 2013, ISSN: 0027-8424.

Abstract | Links:

Rangachari M, Zhu C, Sakuishi K, Xiao S, Karman J, Chen A, Angin M, Wakeham A, Greenfield EA, Sobel RA, Okada H, McKinnon PJ, Mak TW, Addo MM, Anderson AC, Kuchroo VK

Bat3 promotes T cell responses and autoimmunity by repressing Tim-3–mediated cell death and exhaustion.

Journal Article

Nat Med, 18 (9), pp. 1394-400, 2012, ISSN: 1078-8956.

Abstract | Links:

Quintana FJ, Jin H, Burns EJ, Nadeau M, Yeste A, Kumar D, Rangachari M, Zhu C, Xiao S, Seavitt J, Georgopoulos K, Kuchroo VK

Aiolos promotes TH17 differentiation by directly silencing Il2 expression.

Journal Article

Nat Immunol, 13 (8), pp. 770-7, 2012, ISSN: 1529-2908.

Abstract | Links:

Mengshol JA, Golden-Mason L, Arikawa T, Smith M, Niki T, McWilliams R, Randall JA, McMahan R, Zimmerman MA, Rangachari M, Dobrinskikh E, Busson P, Polyak SJ, Hirashima M, Rosen HR

A crucial role for Kupffer cell-derived galectin-9 in regulation of T cell immunity in hepatitis C infection.

Journal Article

PLoS ONE, 5 (3), pp. e9504, 2010.

Abstract | Links:

24 entries « 2 of 3 »
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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 2021-03-31
  • Cellular mechanisms regulating the pathogenesis of secondary progressive CNS autoimmunity, Subvention, Instituts de recherche en santé du Canada, Subvention Projet, from 2018-10-01 to 2023-03-31
  • Centre de recherche du 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 2023-05-01
  • Élucidation des mécanismes immunitaires impliqués dans des maladies autoimmunitaires démyélisantes, Subvention, Fonds de recherche du Québec - Santé, Chercheur-boursier Juniors 1 et 2, Seniors, from 2018-07-01 to 2022-06-30

Recently finished projects

  • 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
  • The role of sex in regulating interleukin-17-mediated toxicity in the central nervous system, Subvention, Instituts de recherche en santé du Canada, Subvention de catalyseur : Intégrer le sexe comme variable dans la recherche biomédicale, from 2018-04-01 to 2020-03-31
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