Grant: Foundation Grant

Immunity; Inflammation; Lipid Mediators; Microparticles; Phospholipase A2; Platelets; Rheumatic Diseases; Rheumatoid Arthritis; Systemic Lupus Erythematosus; Transfusion

<html> <body> <p> <b>Research program</b> Inflammation occurs during innate and adaptive immune responses and in tissue repair, and is either acute or can become chronic and maladaptive. Uncontrolled inflammation can be seen in most, if not all, diseases. However, the mechanisms leading to loss of control of the inflammatory response are misunderstood. While platelets are renowned for their role in hemostasis, accumulating evidence point to a role of platelets in inflammation. Furthermore, platelets bear an extensive cargo, which can be packaged in small vesicles shed from plasma membrane called microparticles. Microparticles can impact other cellular lineages and modify inflammatory responses upon internalization in cell recipient.<br> </p> <p> <b>Vision</b> We use rheumatic diseases and platelet transfusion-induced adverse reactions as relevant contexts of chronic and acute inflammatory conditions, respectively. Rheumatic diseases range from a predominance of joint manifestations to those in which multiple organs (skin, kidney, nervous system) are affected and, very importantly, are associated with blood vessel damage and enhanced risk of death. In line with the reasoning from the tale Le Petit Prince by Saint-Exupery, &ldquo;<i>The essential is invisible to the eye&rdquo;</i>, the understanding of the functions of platelets and of their minuscule particles in disease forms the basis of my <i>Foundation Scheme</i>. I believe that this program will shed light on novel targets for rheumatic disease treatment and prevention of adverse reactions in transfusions, with little or no impact on patient immune system.<br> <br> <b>Expertise</b> My <i>Foundation Scheme</i> takes advantage of the knowledge and leadership that I have acquired on platelets and lipid mediators in inflammation. My laboratory collaborates with H&eacute;ma-Qu&eacute;bec and clinicians from rheumatology and hematology departments. We assess platelet mediators expressed in biological fluids and blood storage bags and we work with bioinformaticians for our data analyses. We also pay attention to the contribution of microparticles in inflammation. For this, my laboratory is equipped with most modern technologies to assess microparticles, quantitatively and qualitatively, and we examine the microparticle elaborated cargo with special interest towards lipid mediators of inflammation. For our mechanistic studies, we include mouse models of arthritis, lupus and transfusion reactions, and we use platelet-specific transgenic mice and intravital imaging.<br> <br> <b>Health outcome</b> If our objectives are met, the knowledge that will culminate from our study of platelet&rsquo;s roles in autoimmune rheumatic diseases will contribute to the comprehension of adverse reactions in transfusion, and vice versa. Technologies to monitor blood labile products can be rapidly implemented, and the identification of novel targets can lead to development of therapeutics in rheumatic disease in longer term. Finally, our findings will contribute to the comprehension of other inflammatory conditions.<br> </p> <p> <b>Mentoring</b> I am a CIHR new investigator with protected time for mentoring. My laboratory currently hosts graduate students, postdoctoral fellows and medical school students. Numerous activities, such as weekly journal club, immunology seminars, lab meetings and international conferences, prepare trainees for transition to their career and accomplishments. The technologies and approaches employed in my laboratories are unique and my laboratory is assuredly a rich environment for the training of highly qualified personnel.</p> </body> </html>