Mast Cells are long-lived tissue resident immune cells that play a pathogenic role in human type 2 allergic inflammatory diseases. Mast cells arise from circulating progenitor cells that mature in peripheral tissues and take on different phenotypes based on their tissue microenvironment, yet little is known about the signals that direct their recruitment to inflamed tissue or their maturation following recruitment.
My laboratory focuses on understanding how mast cells integrate tissue stroma-derived signals cells to take on the discrete mast cell effector phenotypes found within epithelial and subepithelial regions of mucosal tissues, determining how these effector phenotypes change during inflammation and disease, and defining the relative contributions of each phenotype to disease progression. We’ve developed a series of complementary approaches in human and mouse to address these questions. Using single-cell RNA-sequencing, we define the heterogeneous mature mast cell phenotypes found in human disease and map the progression from circulating progenitor to mature mast cell. Through in-vitro modeling and bulk RNA-seq, we test the influence of individual structural cells on mast cell development determine the “fingerprints” of candidate cytokines and growth factors on the mast cell transcriptome. We then can compare our in vitro results to human mast cell transcriptomes in vivo and test the role of specific candidates on mast cell development and function through mouse modeling, taking advantage of several cre-recombinase expressing strains that allow us to specifically target discrete mast cell lineages.