Dr. Jean Charron is an investigator at the Research Centre of the CHU of Québec-Université Laval in the Oncology axis. He is also Professor at the Department of molecular biology, medical biochemistry and pathology in the Faculty of medicine at Université Laval. His research activities focus on the functional characterization of the decision-making mechanisms of the ERK/MAPK signaling pathway in cells when exposed to developmental or environmental cues. These mechanisms are essential for embryonic development and homeostasis of every living throughout life. Any failure of interpretation of cell signalling leads to malformations or pathologies.
Role of the ERK/MAPK pathway in lung development
The development of the respiratory tract is complex and requires several steps of morphogenesis, differentiation and maturation to form the definitive lung. The integration of signals induces by the interaction of secreted factors with their receptors or by cell-cell interactions is essential for lung formation. Dr. Charron’s laboratory examines the role of the ERK/MAPK pathway in lung development using the mouse as a model. His team has already highlighted the role of the ERK/MAPK pathway in lung morphogenesis during bronchial branching and the formation of tracheal cartilage. These defects faithfully recapitulate the phenotypes of significant and costly human diseases, including lung hypoplasia, lung agenesis and tracheomalacia, each representing a major public health concern. These studies will play an increasingly important role in providing insights into the molecular mechanisms underlying fetal and neonatal diseases and in allowing development of novel targeted therapies.
Role of the ERK/MAPK path in the development of autoimmune diseases
The work of the team of Dr. Charron has also shown that decreased ERK/MAPK signaling in hematopoietic cells causes the abnormal production of autoantibodies directed against nuclear proteins and DNA double strand in mice. Over time, these mice develop a glomerulonephritis leading to kidney failure and severe anemia. These symptoms are similar to those of systemic lupus erythematosus (SLE), a severe auto-immune disease more frequent in women than in men. In the murine model generated in the laboratory of Dr. Charron, the females are also 5 times more likely to develop the disease than males. Work is in progress in Dr. Charron’s laboratory to identify which immune cell types are involved in the onset of the auto-immune disease and which molecular mechanisms are involved. This study will provide understanding of the molecular processes leading to the development of autoimmune diseases, and will eventually lead to new therapeutic approaches adapted to sex.
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MEK1 regulates pulmonary macrophage inflammatory responses and resolution of acute lung injury.Journal Article
JCI Insight, 4 (23), 2019, ISSN: 2379-3708.
MEK2 Negatively Regulates Lipopolysaccharide-Mediated IL-1β Production through HIF-1α Expression.Journal Article
J Immunol, 202 (6), pp. 1815-1825, 2019, ISSN: 0022-1767.
Mek1Y130C mice recapitulate aspects of human cardio-facio-cutaneous syndrome.Journal Article
Dis Model Mech, 11 (3), 2018, ISSN: 1754-8403.
Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells.Journal Article
Nature, 548 (7666), pp. 219-223, 2017, ISSN: 0028-0836.
MEK1/2 Inhibition Promotes Macrophage Reparative Properties.Journal Article
J Immunol, 198 (2), pp. 862-872, 2017, ISSN: 0022-1767.
Lung development requires an active ERK/MAPK pathway in the lung mesenchyme.Journal Article
Dev Dyn, 246 (1), pp. 72-82, 2017, ISSN: 1058-8388.
Functional redundancy of the kinases MEK1 and MEK2: Rescue of the Mek1 mutant phenotype by Mek2 knock-in reveals a protein threshold effect.Journal Article
Sci Signal, 9 (412), pp. ra9, 2016.
MEK1 dependent and independent ERK activation regulates IL-10 and IL-12 production in bone marrow derived macrophages.Journal Article
Cell Signal, 27 (10), pp. 2068-76, 2015, ISSN: 0898-6568.
Epithelial inactivation of Yy1 abrogates lung branching morphogenesis.Journal Article
Development, 142 (17), pp. 2981-95, 2015, ISSN: 0950-1991.
ERK (MAPK) does not phosphorylate tau under physiological conditions in vivo or in vitro.Journal Article
Neurobiol Aging, 36 (2), pp. 901-2, 2015, ISSN: 0197-4580.
- 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 de recherche sur le cancer, Subvention, Institutionnel - BDR, BDR - Centres de recherche reconnus, from 1996-05-01 to 2022-06-13
- Role of the ERK/MAPK pathway in intestine development and homeostasis., Subvention, Conseil de recherches en sciences naturelles et génie Canada, Subventions à la découverte SD (individuelles et d'équipe), from 2016-04-01 to 2021-03-31