Regulation of lung stem cells in homeostasis and tumorigenesis. Role of Stress-Activated Protein Kinases

A small pool of lung stem cells, responsible for repairing the gas-exchange tissue, is largely unstudied because researchers could not isolate them until recently. This project will use newly developed culture techniques to investigate how these cells decide whether to renew themselves or transform into the mature cells that line the alveoli. The problem is that when this decision-making process goes wrong, the lung’s ability to maintain its delicate architecture breaks down. That breakdown underlies chronic lung diseases and, most critically, lung cancer—one of the leading causes of death worldwide. Without knowing which molecular signals control stem cell behaviour, researchers cannot design therapies that nudge those cells toward repair instead of tumour formation. This is fundamental science. The immediate output will be a deeper understanding of the proteins—specifically stress-activated protein kinases—that regulate stem cell fate, plus new molecular markers to spot these cells in living tissue. If the findings translate to humans, they could open routes to regenerative therapies for damaged lungs and, potentially, to strategies that block the earliest stages of lung cancer. Past work on stem cell regulation in other tissues has already led to treatments for blood and skin disorders; this project aims to build the same foundational knowledge for the lung.