Research in the Oliver lab centers on enzymes and adaptors of ubiquitin ligase pathways that control T cell tolerance and innate immune cell function. Projects in the lab focus primary on Nedd4-family E3 ubiquitin ligases as many members of this family are essential for T cell function. Since Nedd4-family ligases have domains for substrate binding and enzymatic activity encoded within their structure, it had been suggested that Nedd4-family members might not require adaptor proteins for their function. Our work detailing Ndfip1 as an adaptor for the Nedd4-family E3 known as Itch showed this was not a correct notion. Instead, it raised the possibility that Ndfip1 (and the related protein Ndfip2) are required for multiple Nedd4-family members to function.
Our current research program is based on two fundamental questions: what are the basic immunologic processes that Nedd4-family members control; and how are these E3 ligases regulated by Ndfip proteins? In asking these questions, our initial efforts concentrated on how two Nedd4-family members, Nedd4 and Itch, and Ndfip1, regulate T cell activation, differentiation and cytokine production. More recently we expanded these efforts to define the roles other Nedd4-family members, and the related adaptor Ndfip2, in both innate and adaptive immune cell function.