Monocytes, dendritic cells, and CD4+ T cells, chemokines, chemokine receptors, cell trafficking and T cell costimulation, immunological and virological synapse, HIV-1.
HIV is unique in its ability to target key cells of the immune system and to escape antiviral responses at cellular/molecular level. Current antiretroviral therapy (ART) is a major asset of modern medicine that transformed HIV/AIDS into a manageable chronic disease in countries where access to treatment is possible. However, HIV eradication is not achieved with ART. Our objective is now to generate solid scientific knowledge toward the implementation of new HIV cure/remission strategies. The persistence of HIV reservoirs in small fractions of CD4+ T-cells is very well documented. In contrast the contribution of other immune cell types such as myeloid cells to HIV persistence during ART remains to be established. With this idea in mind, over the past years, the research program of my laboratory was focused on the identification and the molecular characterisation of discrete subsets of CD4+ T-cells and myeloid cells that are permissive versus resistant to HIV infection. The research program of my laboratory is described here below:
Th17 cells and HIV: Our studies placed Th17 cells (a subset of CD4+ T-cells that fight pathogens at mucosal level) at the very core of HIV persistence during ART. This justifies our current efforts toward the identification of Th17-specific transcriptional regulators that can be used as antiviral targets to limit HIV transcription in “block and lock” strategies.
Myeloid cells and HIV: our studies identified CD16+ monocyte-derived dendritic cells as major contributors to HIV pathogenesis and reservoir persistence via the production of soluble pro-inflammatory and immune regulatory molecules. Current researches in the lab are performed to study tissue resident myeloid cells derived from embryonic/foetal precursors (long-lived, self-renewal capacity) versus monocytes (short-lived), in terms of inflammatory potential and contribution to HIV persistence during ART.
Circadian clock and HIV: most recently, one aspect explored in my lab is the importance of circadian rhythms and the cellular circadian clock machinery in the regulation of immunological functions and HIV persistence. There is increasing evidence that the deregulation of the circadian clock is associated with dramatic immunological alterations, mainly in HIV-infected individuals. In addition to their fundamental relevance, these studies are important clinically to orient new HIV eradication strategies, especially the decision of ART interruption.
These studies are in part performed in the context of The Canadian HIV Cure Enterprise (https://www.cancurehiv.org/investigators; PI: Dr. Eric Cohen, Ph.D.), funded by the Canadian Institutes of Health Research (CIHR) in partnership with International AIDS Society (IAS) and Canadian Foundation for AIDS Research (CANFAR). Access to well-characterized longitudinal cohorts of HIV-infected individuals (PI: Dr. Jean-Pierre Routy, M.D.) is facilitated by financial support from the HIV/AIDS Network of the FRQ-S.
Cardiovascular disease and HIV: in parallel, my laboratory is involved in pan-Canadian collaborative efforts to identify cellular and molecular mechanisms of premature aging and cardiovascular disease in the HIV-infected population, including the role of a novel cytokine IL-32. In these studies we benefit from access to the Canadian HIV and aging cohort (PIs: Cécile Tremblay, M.D. and Dr. Madeleine Durand, M.D.). These studies are founded by the CIHR and the National Institutes of Health (NIH).
My laboratory offers great mentoring/training opportunities to graduate and undergraduate students as well as postdoctoral fellows.
Principal Investigator, Canadian HIV Cure Enterprise (CanCURE)
Delphine Planas, Ph.D. Student
Amélie Cattin, Ph.D. Student
Tomas Raul Wiche Salinas, Ph.D. Student
Natalia Fonseca Do Rosario, visiting Ph.D. Student
Etiene Gabriel Moreira, Ph.D. Student
Debashree Chattarjee Adhikari, Ph.D., postdoctoral fellow
Younes Chouikh, Ph.D., Research Assistant
Laurence Raymond Marchand, M.Sc., Research Assistant