Disease Area X
Cambridge, Massachusetts, United States
Many epithelial tissues are maintained by pools of stem cells that differentiate into functional, discrete cell types during homeostasis and following injury. These processes are tightly coordinated to ensure adequate balancing of cell types and maintain organ function. This regenerative capacity is exemplified in the lung epithelium, the “first line of defense” to inhaled particles and pathogens, where continuous environmental damage results in a rapid cellular response to maintain epithelial barrier integrity that resolves with subsequent differentiation to carefully rebalance the functional cell types required for normal gas exchange.
Research in the McCauley lab focuses on understanding the interplay between genetic susceptibility, tissue crosstalk, and gene regulation in normal lung homeostasis and regeneration. The overall goal of this work is to understand the mechanisms contributing to abnormal repair and loss of epithelial identity in disease. We use targeted experimental models, based in primary and iPSC-derived in vitro assay systems, together with gene editing and high-resolution transcriptomic approaches, to elucidate this biology. Currently, we are particularly interested in how regulatory circuits and cell-cell signaling stabilize lung epithelial stem cell identity and control differentiation in homeostasis and injury, to understand the origin and maintenance of abnormal transitional states in disease.