SARAH

Why are some individuals more susceptible to cancer than others? The answer may be hidden in our blood. As we age, the cells that produce our blood can accumulate genetic mutations. These cellular changes can cause the expansion of specific blood cell populations even though there are no obvious signs of blood cancer at this stage. This condition is termed clonal hematopoiesis of indeterminate potential, or CHIP. New studies suggest that CHIP may increase the risk of developing other types of cancer, such as lung cancer. The exact reasons for this are still unclear. However, we suspect that certain blood cells in people with CHIP produce more molecules that promote inflammation. This chronic inflammation may fuel tumor growth and/or reduce the effectiveness of cancer treatments. Our research seeks to unravel the precise relationship between CHIP and lung cancer development. We have engineered sophisticated mouse models that faithfully replicate human lung cancer pathology. Through cutting-edge CRISPR-Cas9 gene-editing technology, we can introduce precise genetic modifications to dissect the mechanisms of cancer initiation and progression. In addition, we validate our laboratory discoveries in tissue specimens from lung cancer patients, ensuring our findings translate to real- world clinical scenarios. We are simultaneously developing innovative therapeutic interventions specifically designed to neutralize CHIP-driven inflammation and immune dysfunction. Rather than viewing tumors in isolation, we are examining the broader cellular ecosystemparticularly how altered blood cells shape the cancer microenvironment. Our objective extends beyond understanding these interactions to identifying predictive biomarkers that could guide personalized treatment decisions and identify patients most likely to respond to targeted interventions. The potential clinical implications are transformative. In the future, we may no longer focus exclusively on destroying tumors but could simultaneously target the aberrant blood cell populations that support cancer growth. This could make existing therapies more effective and significantly improve the survival chances of lung cancer patients.