The molecular mechanisms of T cell MAINTENANCE and DIFFERENTIATION
The successful immune response relies on precision in the differentiation and maintenance of involved cells. Effector T cells defend the organism against pathogenic microorganisms and eliminate malignant or virally infected host cells. To acquire these functions, naïve T cells upon antigen recognition undergo differentiation, the multi-step process that includes activation, proliferation and acquisition of effector functions. After a pathogen is cleared, only a few antigen-specific T cells will survive and give rise to long-lived memory T cells that are essential for the protection of an organism in the event of a secondary antigen encounter. Our laboratory is interested in understanding the regulatory mechanisms that allow T cells to make these decisions and become effector or memory, and what are the specific requirements for their maintenance.
role of non-coding RNAs in T cell survival, proliferation and acquisition of effector function.
identification of key signals and factors that control the initial lineage fate determination of naïve T lymphocytes into effector or memory cells.
Understanding the insides of the IMMUNO-SUPPRESSIVE tumor microenvironment
Chronic inflammation and persistent antigen exposure of T cells lead to alterations in the differentiation program that prevent memory cell formation and promote the generation of exhausted T cells with compromised effector function and poor survival. This is a major concern for the treatment of chronic infections and for adoptive immunotherapy against cancer, where the rapid inactivation/disappearance of antigen specific effector T cells leads to poor clinical outcome. Although in cancer many factors are implicated in establishing the so called “immuno-suppressive tumor microenvironment”, the precise molecular mechanisms are not fully understood. Our laboratory works to define and target such mechanisms in order to develop new therapeutics.
uncovering the molecular pathways that contribute to diversion of functionally competent T cells into the exhausted state.