T cell signalling in autoimmune diseases and cancer

The main goal of our group is the study of the molecular mechanisms that regulate lymphocyte activation and differentiation: a) to understand how dysregulation of theses processes lead to development of human inflammatory disorders, autoimmune diseases or cancer and b) to identify novel therapeutic targets in the treatment of these diseases.

We are dissecting the signaling pathways involved in development of autoimmunity and cancer using a multidisciplinary approach that combines mouse genetic, biochemical, molecular biological and immunological techniques. In particular, we are focus on the function of the Gadd45 (Growth arrest and DNA damage-inducible gene) family and the p38 MAPK (mitogen-activated protein kinase) in lymphocyte activation, differentiation, apoptosis and cytokine production.

We found an important role for Gadd45a in suppression of autoimmunity by regulation of the CD4 +T cells functions. Gadd45a acts as an autoimmune suppressor gene in vivo by negatively regulating T cell proliferation in response to TCR activation. Currently, we are developing and characterizing murine models of autoimmune disease and cancer, analyzing the in vivo and in vitro function of Gadd45 and p38 MAPK in T cell proliferation, apoptosis, and validating these results in autoimmune disease and cancer patients.