Alexander Rudensky

The overall goals of the Rudensky laboratory research are to understand the basic mechanisms of immunoregulation with an emphasis on biology of regulatory T cells and their cellular partners and targets and their roles in autoimmunity, inflammation, tissue degeneration and injury, and cancer. Specifically, the laboratory explores the molecular and cellular mechanisms governing differentiation and function of regulatory T (Treg) cells, a specialized immune cell lineage that acts in a dominant manner to control the body’s immune responses to self-antigens, pathogens, commensal microbiota, allergens, tumors, and abiotic stresses. Rudensky’s laboratory identified the X chromosome-encoded transcription factor Foxp3 as a Treg cell lineage specification factor, elucidated its mode of action and revealed an indispensable role for Treg cells as life-long “guardians” of organismal health. These studies have established a firm genetic foundation for the phenomenon of T cell-mediated suppression of immune mediated inflammation and autoimmunity and elucidated genetic mechanisms supporting Treg cell differentiation, maintenance and function in autoimmunity, cancer, infection, commensal microbiota-host interactions, tissue repair, and pregnancy.  The ongoing projects in the laboratory explore gene regulatory and molecular mechanisms underlying differentiation and function of regulatory T cells in lymphoid and non-lymphoid tissues and roles of cellular circuits they form with diverse cell types of hematopoietic and non-hematopoietic origin in health and disease. In these projects the laboratory employs a diverse range of experimental approaches including reverse genetics, protein biochemistry and proteomics, in vivo and in vitro immunological assays, highly multiplexed imaging, single cell and spatial “omics”, and computational analyses.