The human immune system is a sophisticated defense mechanism which identifies invading pathogens and molecular challenges to coordinate their neutralization and removal Specialized cells known as T and B lymphocytes are key effectors of the adaptive immune response Lymphocyte development is tightly controlled to prevent the expansion of destructive, self-reactive T and B cells and the development of autoimmune diseases Themis1 and Themis2, two recently described T cell specific proteins, are key regulators of T cell development Intriguingly, Themis proteins have been shown to interact with Grb2 and SHP-1, two essential adaptor proteins in intracellular signaling cascades  Accumulating evidence has linked Themis proteins to inflammatory diseases, such as inflammatory bowel disease, yet the structural and mechanistic basis of these functions remain poorly understood

The objective of this research program is to provide timely insights into the structure and function of Themis1 and Themis2 and to investigate the unexplored role of these proteins in inflammatory signaling Elucidation of Themis1 and Themis2 structural domains, particularly the CABIT domain, and how they interact with signaling partners will provide insights into the function of Themis proteins as a possible nexus in inflammatory pathways Thus, we envisage that our work will impact the development of novel therapeutic strategies to target Themis activities in inflammatory diseases

The human immune system is a sophisticated defense mechanism which identifies invading pathogens and molecular challenges to coordinate their neutralization and removal. Specialized cells known as T and B lymphocytes are key effectors of the adaptive immune response. Lymphocyte development is tightly controlled to prevent the expansion of destructive, self-reactive T and B cells and the development of autoimmune diseases. Themis1 and Themis2, two recently described T cell specific proteins, are key regulators of T cell development. Intriguingly, Themis proteins have been shown to interact with Grb2 and SHP-1, two essential adaptor proteins in intracellular signaling cascades. Accumulating evidence has linked Themis proteins to inflammatory diseases, such as inflammatory bowel disease, yet the structural and mechanistic basis of these functions remain poorly understood.

The objective of this research program is to provide timely insights into the structure and function of Themis1 and Themis2 and to investigate the unexplored role of these proteins in inflammatory signaling. Elucidation of Themis1 and Themis2 structural domains, particularly the CABIT domain, and how they interact with signaling partners will provide insights into the function of Themis proteins as a possible nexus in inflammatory pathways. Thus, we envisage that our work will impact the development of novel therapeutic strategies to target Themis activities in inflammatory diseases.