Mickaël MénagerInflammatory responses and transcriptomic networks in diseases - Institut Imagine / Université de Paris.
Mes recherches
I am the lab director of the “Inflammatory responses and transcriptomic networks in diseases” Team and Researcher (CRCN, 2017) at the French National Institute of Health and Medical Research (Inserm). In 2016, I am the laureate of the ATIP-Avenir call with a project aiming at better understanding the interactions between HIV-1 and dendritic cells. The same year, I am also becoming a group leader at the Imagine Institute to explore the complexity of the innate immune response and autoinflammation by combining single-cell transcriptomic and chromatin accessibility experiments with machine learning computational biology tools. I obtained my PhD with Geneviève de St-Basile at the Necker Hospital in 2008 before joining, as Postdoctoral Fellow for 7 years, Dan Littman’s laboratory at the Skirball Institute, NYU School of Medicine, USA. Since the ATIP-Avenir, I received, amongst others supports, the Janssen Horizon Grant (2017), the Emergence Ville de Paris grant (2018) and the Sanofi European iAwards (2018). I am also group leader of several work packages of the ATRACTion RHU4 project (recently financed by the ANR), where in collaboration with several academic and industrial partners, we will use single-cell OMICs coupled with machine-learning based analyses to better stratify, diagnose and discover new treatments for patients suffering from rare genetic autoimmune/autoinflammatory diseases.
Mon projet ATIP-Avenir
Understanding the molecular and cellular biology behind the interactions between viruses and Dendritic cells.
Dendritic cells (DCs) bridge innate and adaptive immunity. They are present, in an immature state, in organs and mucosal tissues. They may sequentially: engulf elements from their environment; sense engulfed pathogens, which may trigger inflammatory cytokine secretion and their maturation; migrate to lymph nodes and present antigens to T lymphocytes. Although DCs are relatively resistant to infection by HIV-1, they are able to enhance CD4+ T cell infection in a processed termed trans-infection. By doing that, HIV-1 may evade, at least in part, the first line of defense of the immune system, exploiting DCs instead to facilitate rapid infection of a large pool of immune cells. Here, we seek to investigate the crosstalk between DC maturation, actin nucleation, interferon production (IFN) and Tspan7 to better understand mechanisms of HIV transfer from DC to T cells. Transcriptional programming of the innate immune response to HIV is pivotal for host protection. During infection with HIV-1, human dendritic cells (DCs) can detect the virus through an innate sensing pathway leading to antiviral interferon and DC maturation. We also developed an iterative experimental and computational approach to map the innate response circuitry during HIV-1 infection in monocyte-derived DCs (MDDCs).