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.
2705, boulevard Laurier, T-2-50
Canada G1V 4G2
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Protein translocation and retro-translocation across the endoplasmic reticulum are crucial to inflammatory effector CD4(+) T cell function.Journal Article
Cytokine, 129 , pp. 154944, 2020, ISSN: 1043-4666.
Profiling of how nociceptor neurons detect danger - new and old foes.Journal Article
J Intern Med, 286 (3), pp. 268-289, 2019, ISSN: 0954-6820.
Publisher Correction: The metabolite BH4 controls T cell proliferation in autoimmunity and cancer.Journal Article
Nature, 572 (7769), pp. E18, 2019, ISSN: 0028-0836.
Peripheral adaptive immunity of the triple transgenic mouse model of Alzheimer's disease.Journal Article
J Neuroinflammation, 16 (1), pp. 3, 2019.
Tim-3: A co-receptor with diverse roles in T cell exhaustion and tolerance.Journal Article
Semin Immunol, 42 , pp. 101302, 2019, ISSN: 1044-5323.
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 , pp. 3115, 2019, ISSN: 1664-3224.
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.
Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling.Journal Article
Cell Rep, 22 (5), pp. 1301-1312, 2018.
The metabolite BH4 controls T cell proliferation in autoimmunity and cancer.Journal Article
Nature, 563 (7732), pp. 564-568, 2018, ISSN: 0028-0836.
Editorial: Lymphocytes in MS and EAE: More Than Just a CD4+ World.Journal Article
Front Immunol, 8 , pp. 133, 2017, ISSN: 1664-3224.
- 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 2020-10-18
- 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
- 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
- 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