Our laboratory studies molecular mechanisms of T cell activation and differentiation, and innate immune responses regulated by E3 ubiquitin ligases Cbl-b and Nedd4. We have identified several novel proteins targeted by Cbl-b in T cells and innate immune cells, and are investigating 1) whether and how Cbl-b regulates the development of T follicular helper cells (TFH) and innate lymphoid cells; 2) how Cbl-b regulates the innate immune cells sensing Candida albicans and other fungi; and 3) how Cbl-b controls sepsis and septic shock. In addition, we have also identified some novel substrates of Nedd4 in T cells, is studying Nedd4 in T helper cell development and autoimmunity. Further understanding of these E3 ubiquitin ligases in innate and adaptive immunity will lead to the development of therapeutic invention for human diseases such as multiple sclerosis, allergic asthma, lupus, and infectious diseases.