Our laboratory studies the mechanisms that regulate T cell function in humans. We use a range of approaches including cellular immunology, functional genomics and chemical biology to understand why protective T cell memory fails to occur in cancer and chronic viral infection.
Our work focuses on understanding the molecular differences between functional CD8 T cells and dysfunctional, exhausted CD8 T cells that are characteristic of chronic infection. For example, we have used transcriptional profiling of rare populations of virus-specific CD8 T cells from human blood to identify the molecular differences between effective and ineffective T cell responses in HIV.
These studies have uncovered a mechanism by which the inhibitory receptor PD-1 upregulates a novel transcription factor, BATF, that impairs T cell function.
We are also interested in developing novel therapeutic approaches to rescue function in exhausted T cells. We are using chemical screens to identify small molecules that reverse the inhibition caused by the receptor PD-1, and are developing novel genetic and computational approaches to match active compounds to their target molecules.