Research in our laboratory includes the following areas:

• Molecular mechanisms involved in the control of inflammation

The inflammatory response, elicited by pathogens or danger signals is critical for the initiation of immune responses. It involves molecules that will directly target infectious organisms and mediators such as chemokines and cytokines that will attract and educate other immune cells. This process has to be tightly controlled as acute inflammation can lead to tissue damage and chronic inflammatory states that are associated with a broad range of diseases, including autoimmunity, atherosclerosis and cancer. A few key cytokines that are expressed by the mononuclear phagocyte system (monocytes, macrophages and dendritic cells) help dictate the type of adaptive immune response elicited in response to a pathogen.
We are interested in the developmental plasticity of the mononuclear phagocyte system and the control of cytokine production in the context of infection, chronic inflammation and cancer. These projects focus on the role of epigenetic regulation and mRNA destabilization. They involve transcriptomic and epigenomic approaches, pre-clinical animal models, the development of a humanized mice platform and collaborations with clinicians. Recently, we also evaluate the impact of infections (such as SARS-Cov2) on innate immune cell function.

• Transcriptional control of CD8 T cell differentiation

In the context of acute infection or immunization, naïve CD8 T cells that encounter their cognate antigen in lymphoid organs undergo expansion and activation. In a matter of days, they acquire expression of effector functions that contribute to pathogen clearance. While the majority of primed T cells undergo terminal differentiation into effector cells and ultimately die, a few percent will form long-lived memory after the infection is cleared. Such memory cells are epigenetically programmed for more rapid and effective response upon re-stimulation with antigen. However, in the context of cancer, persistent antigenic stimulation and tumor-derived immunosuppressive factors may lead to alteration of these differentiation steps and progressive loss of effector functions. In the last decade, tremendous efforts have been dedicated to define the cellular and molecular mechanisms involved in these physiological and pathological processes. We are trying to define the transcriptional and epigenetic basis of memory formation and cancer-related dysfunction. We are particularly interested in the role of Eomesodermin, a key transcription factor that regulates T cell differentiation.