Abstract

The wealth of somatic mutations that our cells accumulate over time provides a valuable resource for understanding how populations of cells evolve in the context of health and disease. Somatic evolution studies of the adaptive immune system can reveal the patterns of immune response and proliferation. One key tool for these studies is phylogenetic lineage tracing, which can be used to time events in the past. With single-cell whole genome sequencing, one can build a phylogenetic tree of cells within an individual, read out the age of lymphocyte expansions and identify any mutations of functional consequence. Here, I will describe two studies where I develop the tools needed for phylogenetic lineage tracing in T cells. The first performs phylogenetic timing of hematopoeitc stem cells in Shwachman-Diamond Syndrome. The second describes the mutational landscape of the adaptive immune system with age. I will then explain how studying the somatic evolution of the adaptive immune response to cancer can be used to address some of most compelling questions in cancer immunology.