Grant: Foundation Grant

Adaptive Immunity; Cell Death Program; Eicosanoids; Immunity To Pulmonary Infections; Influenza Virus; Innate Immunity; Macrophage Biology; Mouse Models; Mycobacterium Tuberculosis; Pulmonary Immunology

<html> <body> <p> <strong>Summary:</strong> Globally, respiratory infections cause more than 4 million deaths per year, with influenza and tuberculosis (TB) in particular being major causes of mortality and morbidity. Although an immune response is required for killing respiratory pathogens, this immunity must be tightly regulated to effectively eliminate invading microorganisms while minimizing immunopathology, which leads to pulmonary dysfunction. The distinctive microenvironment of lung is constantly patrolled by alveolar macrophages (M&#x03c6;), which are essential in early pathogen-recognition, initiation of immunity, and resolution of inflammation. <strong><em>The specific goal of my research program</em></strong> is to investigate the regulatory mechanisms of M&#x03c6; in the setting of infections by two major pulmonary pathogens, influenza virus and TB. By focusing on both acute viral and chronic bacterial infections we will define a spectrum of the regulatory mechanisms involved in M&#x03c6; immunity that determine the ultimate outcome of infection. We envision that mitochondria is the master regulator of M&#x03c6; by controlling cell metabolism, death and type I IFN. We foresee that harnessing the biological properties of M&#x03c6; by either novel immunomodulatory of eicosanoids (<strong><em>short-term</em></strong>) or hematopoietic stem cell-based vaccine (<strong><em>long-term</em></strong>) will allow for improved preventative and therapeutic strategies for TB and influenza infections. The importance of my research program is reflected by success in obtaining funding to support my program (including 2 CIHR-grants as PI).<br> </p> <p> <strong>Experience/expertise.</strong> As a pulmonary immunologist, I have been involved in research focusing on immunity to pulmonary infection for the last 15 years. The multi-faceted program which I have developed by incorporating metabolomic, transcriptomic, epigenetic as well as unique <em>in vitro</em> and <em>in vivo</em> experimental models will advance our basic understanding of host-pathogen interactions during pulmonary infections in general, with potential applications to many other infectious agents.<br> </p> <p> <strong>Collaborations.</strong> Since establishing my lab in 2010, I have assembled strong collaborations locally, nationally, and internationally. With all the indicated collaborators I either have a CIHR-grant or published paper. Dr. Russell Jones (expert in Metabolism, U.McGill), Dr. White (expert in gene regulation, U.McGill), Dr. Barreiro (expert in epigenetic, U.Montreal), Dr. McCullers (expert virologist, Tennessee), Dr. Behr (expert in mycobacteriology), Dr. Menzies (clinical TB epidemiologist, U.McGill), Dr. Tabrizian (expert in nanotechnology, U.McGill), and Dr. Kobinger (expert virologist, Public Health Agency of Canada) we determine the contribution of eicosanoids to protection against the 1918 Spanish influenza virus.<br> </p> <p> <strong>Mentoring/Training.</strong> As I have two 5-years CIHR-grants one to study TB and the other one to study influenza, I have divided my personnel in my lab in two teams, TB-Team and Influenza-Team. Each team consists of one PDF or RA, one or two Graduate Student, and one Undergraduate Student. Although each trainee has its own independent project, as pulmonary M&#x03c6; is the common theme between two groups, both team are extremely interactive and collaborative. All trainees participate in weekly lab-meeting that provide each trainee the opportunity to give in-depth presentations of their work and receive critique and suggestions. In addition, I have one-on-one meeting with each individual trainees every two weeks providing them thoughtful and constructive feedbacks.<br> <br> </p> </body> </html>