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
T-1-49
Québec, Québec
Canada G1V 4G2

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Bigonnesse F, Lévesque SA, Kukulski F, Lecka J, Robson SC, Fernandes MJ, Sévigny J

Cloning and characterization of mouse nucleoside triphosphate diphosphohydrolase-8.

Journal Article

Biochemistry, 43 (18), pp. 5511-9, 2004, ISSN: 0006-2960.

Abstract | Links:

Barabé F, Paré G, Fernandes MJ, Bourgoin SG, Naccache PH

Cholesterol-modulating agents selectively inhibit calcium influx induced by chemoattractants in human neutrophils.

Journal Article

J Biol Chem, 277 (16), pp. 13473-8, 2002, ISSN: 0021-9258.

Abstract | Links:

Barabé F, Rollet-Labelle E, Gilbert C, Fernandes MJ, Naccache SN, Naccache PH

Early events in the activation of Fc gamma RIIA in human neutrophils: stimulated insolubilization, translocation to detergent-resistant domains, and degradation of Fc gamma RIIA.

Journal Article

J Immunol, 168 (8), pp. 4042-9, 2002, ISSN: 0022-1767.

Abstract | Links:

Fernandes MJ, Iscove NN, Gingras G, Calabretta B

Identification and characterization of the gene for a novel C-type lectin (CLECSF7) that maps near the natural killer gene complex on human chromosome 12.

Journal Article

Genomics, 69 (2), pp. 263-70, 2000, ISSN: 0888-7543.

Abstract | Links:

Fernandes MJ, Finnegan AA, Siracusa LD, Brenner C, Iscove NN, Calabretta B

Characterization of a novel receptor that maps near the natural killer gene complex: demonstration of carbohydrate binding and expression in hematopoietic cells.

Journal Article

Cancer Res, 59 (11), pp. 2709-17, 1999, ISSN: 0008-5472.

Abstract | Links:

Fernandes MJ, Hechtman P, Boulay B, Kaplan F

A chronic GM2 gangliosidosis variant with a HEXA splicing defect: quantitation of HEXA mRNAs in normal and mutant fibroblasts.

Journal Article

Eur J Hum Genet, 5 (3), pp. 129-36, 1997, ISSN: 1018-4813.

Abstract | Links:

Fernandes MJ, Yew S, Leclerc D, Henrissat B, Vorgias CE, Gravel RA, Hechtman P, Kaplan F

Identification of candidate active site residues in lysosomal beta-hexosaminidase A.

Journal Article

J Biol Chem, 272 (2), pp. 814-20, 1997, ISSN: 0021-9258.

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Active projects

  • A comprehensive analysis of low-density neutrophils in cystic fibrosis : a functional biomarker study, Subvention, Fonds de recherche du Québec - Santé, from 2020-01-01 to 2020-12-31
  • Caractérisation de la viabilité et de la fonction des granulocytes destinés à la transfusion, Partenariat, MITACS Inc., Accélération Québec (MITACS/MEIE), from 2019-09-15 to 2021-11-14
  • 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
  • Développement d'une nouvelle drogue anti-inflammatoire qui est moins toxique et plus efficace que la colchicine , Subvention, Fondation du CHU de Québec, from 2020-06-09 to 2021-03-31

Recently finished projects

  • Assessment of the Quality of Granulocyte Concentrates to Optimise their use in Transfusion Therapy., Subvention, Société canadienne du sang, from 2018-12-01 to 2019-11-30
  • Centre de recherche en arthrite de l'Université Laval, Subvention, Institutionnel - BDR, BDR - Entités de recherche en émergence, from 2019-01-01 to 2020-01-31
  • Évaluation des neutrophiles de faible densité en tant que biomarqueurs et modulateurs de la fonction pulmonaire et de la progression de la fibrose kystique., Subvention, Le Grand Défi Pierre Lavoie, Subvention pour projet de recherche sur une maladie héréditaire orpheline, from 2018-10-01 to 2019-09-30
  • The characterization of MICL, a novel negative regulator of the immune response in arthritis., Subvention, Instituts de recherche en santé du Canada, Subvention de fonctionnement, from 2015-07-01 to 2020-06-30
  • The development of a novel anti-inflammatory drug to treat gout, Subvention, Fondation du CHU de Québec, from 2018-04-09 to 2020-03-31
Data provided by the Université Laval research projects registery