Michael S. Kuhns, Ph.D.

Research

Effective immunity to pathogens requires that coordinated, multi-cellular responses emerge from a myriad of “conversations” that take place between cells of the innate and adaptive immune compartments. My lab is working to understand the molecular mechanism that mediate the conversations that occur between antigen-presenting cells and T cells that determine if and how a T cell responds to antigen. We are using a variety of classic molecular, cellular, biochemical, imaging, and evolutionary techniques to probe these processes. We are also developing mouse model systems to determine how individual mechanisms contribute to T cell responses during pathogenic infection or autoimmunity. Altogether, our work is aimed at increasing our basic and practical understanding of T cell activation and regulation.

As an Innovation Fund investigator, Michael Kuhns, Ph.D., is teaming up with Nels Elde, Ph.D., to study the functional consequences of interspecies differences in the structure of immunoglobulin (Ig) domains, key building blocks for proteins that mediate immunity. After computationally reconstructing the evolutionary history of the T-cell protein CD4, the team found that the protein’s Ig-domain structures are different in fish versus mammals. They hypothesize that these structural differences have consequences for core T-cell functions. To test this hypothesis, the Elde lab will generate transgenic zebra fish expressing fish CD4 with Ig domains resembling those of mice, while the Kuhns lab will generate mouse T-cell hybridoma cell lines expressing mouse CD4 with Ig domains resembling those of fish. Both labs will perform expression and functional analyses to understand how these Ig domain changes influence function. Ultimately, the pair aims to better understand immune system function by comparing key differences between species.