We use preclinical models to study polyclonal T cell responses to bone marrow-resident tumors. We validate key findings in human samples. One of our areas of focus is a terminally exhausted T cell subset that retains functional capacity (TPHEX; phenotypically exhausted). We aim to uncover the transcriptional and epigenetic factors that preserve function in these cells. We also study the tumor microenvironment to understand what external signals are required for the differentiation and maintenance of this subset. Single-cell RNA sequencing, spatial transcriptomics, and high-parameter flow cytometry are instrumental to our goal of deeply profiling the immune system. 

Minnie & Waltner et al. Science Immunology 2024