Dr. Irma Bernatchez-Lemaire

Biography

Recipient of:

• CIHR-CNR International Award for Invited Scientist, Università di Ferrara, Italy
• MRC-INSERM International Award for Invited Scientist, Université Montpellier, France
• MRC Scientist Scholar, University of Ottawa
• FRSQ (Fonds de la Recherche en Santé du Québec) Scientist Scholar, Université de Sherbrooke
• Recognition Award for Outstanding Contribution to Medical Education, Faculty of Medicine, University of Ottawa
• Award of Excellence, Faculty of Medicine, University of Ottawa
• MRC postdoctoral fellowship, University of California, San Francisco Medical Center, USA
• MRC postdoctoral fellowship, Columbia University, New York, USA

Research interests:

Macrophage recruitment and plasticity are key components of several chronic disorders including various autoimmune diseases (Crohn’s disease, rheumatoid arthritis, multiple sclerosis, autoimmune hepatitis), atherosclerosis, fibrotic diseases, obesity, type 2 diabetes, asthma and cancer. Understanding the mechanisms that regulate macrophage phenotype and function in tissues is critical for the identification and validation of markers and therapeutic targets in inflammatory conditions.  We focused on two major aspects:  Purinergic signaling in macrophage fusion and the formation of multinucleated giant cells, a hallmark of chronic inflammation. This area of research concerns the underlying mechanisms that regulate macrophage fusion to form multinucleated giant cells. We showed the physiological/pathological relevance of the purinergic P2X7 receptor for extracellular ATP as a critical effector of MA fusion in response to the inflammatory cytokine GM-CSF. Recently, we have identified a new P2X7/ATP/Adenosine signaling pathway critical for efficient promotion of macrophage fusion. Our data also provided the first evidence for the participation of the hemichannel protein Pannexin-1 in this process. We are currently investigating the role of P2X7 in the expression of crucial fusiogenic molecules.

The P2X7 as a relevant target for the control of inflammation. Of paramount importance for the control of dysregulated inflammatory responses is the understanding of the signal(s) required to switch macrophages into a pro-inflammatory state. Stimulation of the P2X7 receptor in macrophages is linked to activation of the inflammasome and production of inflammatory cytokines and mediators including IL-1, IL-6, IL-8 and MMP-9.  Work from our laboratory suggests that the P2X7 receptor may represent an amplification pathway for inflammation. Interestingly, we have identified a class of H4-related peptides that interfere with P2X7-mediated functions in vitro and in vivo. We are investigating the mechanisms of action of these peptides at the P2X7 receptor level.

Selected publications:

• Lemaire I., Falzoni S., Adinolfi A. Purinergic signaling in giant cell formation.  Frontiers in Biosciences (Elite. Ed.), 4: 41-55, 2012
• Lemaire I. Falzoni S., Zhang B., Pellegatti P., Di Virgilio F. The P2X7 receptor and Pannexin-1 are both required for the promotion of Multinucleated Macrophages by the Inflammatory Cytokine GM-CSF.  J. Immunol. 187: 3878-3887, 2011
• Pellegatti P., Falzoni S, Donvito G. Lemaire I.,  Di Virgilio F. P2X7 receptor drives osteoclast fusion by increasing the extracellular adenosine concentration. FASEB J. 25: 1264-1274, 2011.
• Lemaire I., Falzoni S., Leduc N., Zhang B., Pellegatti, Chiozzi P, Adinolfi E.,Di Virgilio F. Involvement of the purinergic P2X7 receptor in the formation of multinucleated giant cells. J. Immunol., 177, 7257-7265, 2006 (cover, November 15, issue).
• Di Virgilio F., Lemaire I. Purinergic signalling in inflammation and immunomodulation. CRC Reviews., “ Nucleotides in the regulation of bone formation and resorption” pp. 159-193, October, 2006.
• Poirier R., Lemaire I., Lemaire S. Characterization, localization and possible anti-inflammatory function of rat histone H4 mRNA variants. FEBS J., 273, 4360-4373, 2006.
• René Poirier, Irma Lemaire, Michel Dumont, Natacha Leduc, Hoang-Thanh Le, Simon Lemaire. Correlation between the expression of the histone H4 mRNA variant H4-v.1 and the levels of histone H4 -(86B100) and H4-(89B102) (OGP) in various rat tissues and alveolar macrophages. Peptides, 26,1503-1511 2005
• Le H.T., Lemaire I.., Gilbert A.K., Jolicoeur F., Yang L., Leduc N.,Lemaire S. Histogranin-like antinociceptive and anti-inflammatory derivatives of o-phenylenediamine and benzimidazole. J. Pharmacol. Exp. Ther. , 309 , 146-155, 2004.
• Le H.T., Lemaire I.., Gilbert A.K., Jolicoeur F., Lemaire S. Bioactive peptidic analogues and cyclostereoisomers of minimal antinociceptive Histogranin fragment-(7-10).J. Medicinal Chem., 46, 3094-3101, 2004.
• Lemaire I., Leduc N. Characterization of purinergic P2X7 receptor function in lung alveolar macrophages: bidirectional regulation by Th1/Th2 cytokines. Drug Dev. Res., 59, 118-127, 2003.
• Lemaire I., Yang H., Lafont V., Dornand J., Commes T., Cantin M.-F.  Differential effects of M-CSF and GM-CSF on cytokine gene expression during alveolar macrophage differentiation into multinucleated giant cells (MGC): Role for IL-6 in Type 2 MGC formation.  J. Immunol., 157, 5118-5125, 1996.
• Lemaire I., Yang H., Lauzon W., Gendron N. M-CSF and GM-CSF promote alveolar macrophage differentiation into multinucleated giant cells with distinct phenotypes.  J. Leukoc. Biol., 60, 509-518, 1996.
• Lemaire I., Yang H.  Colony stimulating factors induce alveolar macrophage differentiation and giant cell formation.  Ann. N.Y. Acad. Sci., 297-309, 1996.
• Lemaire S., Rogers C., Dumont M., Shukla V.K., Lapierre C., Prasad J., Lemaire I.  Histogranin, a modified histone H4 fragment endowed with N-methyl-D-aspartate antagonist and immunostimulatory activities.  Life Sciences, 56, 1233-1241, 1995.
• Lemaire I., Yang H., Cantin MF., Lemaire S.  Regulation of cytokine production in alveolar macrophages by histogranin, a novel endogenous pentadecapeptide.  Immunol. Letters, 41, 37-42, 1994.
• Lemaire I., Cantin MF., Lemaire S.  Phencyclidine (PCP)-like peptide, histogranin, modulates cell-mediated immune function.  Regul. Peptides, Suppl. 1, S261-S262, 1994.
• Lemaire S., Griffiths J., Lapierre C., Lemaire I., Merali Z., Ravindran AV.  Characterization of histogranin receptors in human peripheral blood lymphocytes.  Biochem. Biophys. Res. Commun., 194, 1323-1329, 1993.