I am an associate professor in the department of Microbiology-Infectiology and Immunology, at the Laval University School of Medicine, and a member of the Infectious Diseases and Immunology Axis of the CHUQ Research Center, CHUL Pavilion.

I did my PhD at McGill University in molecular genetics and my post-doctoral studies at Thomas Jefferson University (Philadelphia) in cancer, during which I cloned two new genes that code for C-type lectin receptors. During my subsequent post-doctoral work at Laval University, my research focused on neutrophil biology, and specifically on signaling. The current research in my laboratory brings together these three fields of research, namely, genetics, C-type lectin receptors, and innate immunity.

The overall goal of the research in my laboratory is to further our understanding of the immunopathogenesis of two types of arthritis, namely rheumatoid arthritis and gout. Arthritis refers to a group of diseases that affect the joints and cause pain and inflammation. There are over 100 types of arthritis. Although drugs are available to treat different types of arthritis, many medications are associated with secondary side effects, and some patients don’t respond to available drugs. To address this unmet need, we must gain more insight into the pathogenesis of these diseases to develop more effective and less toxic drugs.

Our research revealed that the C-type lectin receptor known as Clec12A is involved in the pathogenesis of rheumatoid arthritis and gout. This discovery provides insight into one of the mechanisms through which the immune system is deregulated in these diseases. Clec12A is an inhibitory receptor that is expressed by the innate immune cells of the myeloid lineage, such as neutrophils and monocytes. It is also expressed by dendritic cells. Our current working hypothesis is that in gout and rheumatoid arthritis, the Clec12A inhibitory pathway is not fully functional, causing myeloid cells to be more easily activated.

We use a multidisciplinary approach to gain insight into how Clec12A works to determine its contribution to the pathogenesis of arthritis, with the goal of eventually transferring our findings to clinical practice. The molecular and cellular biology tools we use will shed light on how Cle12A dampens the activation of immune cells. To complement this line of research, the more clinical aspect of our Clec12A project involves the analysis of patient samples to better understand the potential role of this inhibitor in chronic inflammatory diseases (e.g.: gout and rheumatoid arthritis).

Another aspect of our research involves the development of a new anti-inflammatory drug to treat gout, using a rational drug design approach. This new drug may also have the ability to dampen inflammation in patients suffering from other inflammatory diseases.

In summary, our research aims to further our understanding of the pathogenesis of gout and rheumatoid arthritis, identify biomarkers for these diseases, as well as develop a new anti-inflammatory drug that is less toxic and more potent than those used to currently treat gout and other chronic inflammatory diseases. The results of this research will also shed light on the role of Clec12A in other chronic inflammatory diseases, since the Clec12A pathways also seem to be dysregulated in Crohn’s disease.

CHUL
2705, boulevard Laurier
T1-49
Québec, Québec
Canada G1V 4G2
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Andréa M, Nathalie V, Andrée-Anne T, Lise C, Myriam V, Marie-Michèle L, Yves B, Guillaume B, Damien A, Emmanuelle B, Sylvie L, Nicolas F, Lara B, Fernandes MJ

Association of low-density neutrophils with lung function and disease progression in adult cystic fibrosis

Journal Article

J Cyst Fibros, 2023.

Abstract | Links:

McLeish KR, Fernandes MJ

Understanding inhibitory receptor function in neutrophils through the lens of CLEC12A

Journal Article

Immunol Rev, 314 (1), 2023.

Abstract | Links:

Murru A, Allard MÈ, Paré G, Vaillancourt M, Boyer L, Cayer MP, Vitry J, Landry P, Labrecque MM, Robitaille N, Branch DR, Girard M, Fernandes MJ

Comparison of Neutrophil Function in Granulocyte Concentrates From Prednisone- and G-CSF-Treated Donors: Effect of Stimulant, Leukapheresis and Storage

Journal Article

Front Med (Lausanne), 9 , 2022.

Abstract | Links:

Vitry J, Paré G, Murru A, Charest-Morin X, Maaroufi H, McLeish KR, Naccache PH, Fernandes MJ

Regulation of the Expression, Oligomerisation and Signaling of the Inhibitory Receptor CLEC12A by Cysteine Residues in the Stalk Region

Journal Article

Int J Mol Sci, 22 (19), 2021.

Abstract | Links:

Paré G, Vitry J, Merchant ML, Vaillancourt M, Murru A, Shen Y, Elowe S, Lahoud MH, Naccache PH, McLeish KR, Fernandes MJ

The Inhibitory Receptor CLEC12A Regulates PI3K-Akt Signaling to Inhibit Neutrophil Activation and Cytokine Release

Journal Article

Front Immunol, 12 , 2021.

Abstract | Links:

Vaillancourt M, Desaulniers P, Paré G, Pagé N, Lachhab A, Kerever A, Julien AS, Amiable N, Pelletier M, Tessier PA, Bessette L, Michou L, Fortin PR, Fernandes MJ

Expression of the myeloid inhibitory receptor CLEC12A correlates with disease activity and cytokines in early rheumatoid arthritis

Journal Article

Sci Rep, 11 (1), 2021.

Abstract | Links:

Pare G, Vitry J, Marceau F, Vaillancourt M, Winter P, Bachelard H, Naccache PH, Tuszynski JA, Fernandes MJ

The development of a targeted and more potent, anti-Inflammatory derivative of colchicine: Implications for gout

Journal Article

Biochem Pharmacol, 180 , 2020.

Abstract | Links:

Zhao C, Amiable N, Laflamme M, Marsolais D, Di Battista JA, Fernandes MJ, Bourgoin SG

Impairment of chemical hypoxia-induced sphingosine kinase-1 expression and activation in rheumatoid arthritis synovial fibroblasts: A signature of exhaustion?

Journal Article

Biochem Pharmacol, 165 , 2019.

Abstract | Links:

Fernandes MJ, Naccache PH

The Role of Inhibitory Receptors in Monosodium Urate Crystal-Induced Inflammation

Journal Article

Front Immunol, 9 , 2018.

Abstract | Links:

Rousseau LS, Pare G, Lachhab A, Naccache PH, Marceau F, Tessier P, Pelletier M, Fernandes M

S100A9 potentiates the activation of neutrophils by the etiological agent of gout, monosodium urate crystals

Journal Article

J Leukoc Biol, 102 (3), 2017.

Abstract | Links:

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Active projects

  • Cryopreservation of human neutrophils as a source of innate immune defenses for neutropenicpatients with life-threatening infections - Soutien facultaire, from 2023-04-01 to 2024-03-31
  • Optimisation de l'efficacité antimicrobienne des dons de granulocytes destinés à la transfusion, from 2021-09-01 to 2023-10-31

Recently finished projects

  • A comprehensive analysis of low-density neutrophils in cystic fibrosis : a functional biomarker study, from 2020-01-01 to 2023-03-31
  • Caractérisation de la viabilité et de la fonction des granulocytes destinés à la transfusion, from 2019-09-15 to 2021-11-14
  • Développement d'une nouvelle drogue anti-inflammatoire qui est moins toxique et plus efficace que la colchicine , from 2020-06-09 to 2023-03-31
  • Évaluation d'un nouvel anti-corps dans l'arthrite rhumatoïde comme biomarqueur potentiel, from 2022-07-11 to 2023-03-31
  • Évaluation d’un nouvel auto-anticorps dans l'arthrite rhumatoïde comme biomarqueur potentiel, from 2022-10-01 to 2023-09-30
  • FGR - Caractérisation du rôle des microtubules (MT) dans les neutrophiles, from 2022-09-20 to 2023-09-19
  • Le rôle inhibiteur de CLEC12A dans lesmaladies autoimmunes : complexes immuns et neutrophiles, from 2023-05-08 to 2023-09-30
  • Les transfusions de granulocytes: l'optimisation de l'entreposage des concentrés de granulocytes et le rôle antimicrobien des monocytes, from 2021-04-01 to 2022-03-31
  • Subvention d'appariement à la programmation de recherche, from 2020-04-01 to 2022-03-31
Data provided by the Université Laval research projects registery