Catherine Rufatto Sears, MD

Lung cancer and chronic obstructive pulmonary disease (COPD) are common and fatal lung diseases. both linked to older age and cigarette smoking. Also, they both commonly develop in the same patient, as COPD increases the risk of lung cancer. Reduced DNA repair is implicated in both, but the mechanisms are poorly understood. We discovered a critical role of the DNA repair protein Xeroderma Pigmentosum Group C (XPC) in protecting against both lung cancer and COPD development in mice. We will use a mouse model to study how DNA repair deficiency impacts lung cells in response to cigarette smoke, leading to development of lung cancer and COPD. We will use this model to understand the interaction between the tumor and local lung environment, as well as the development of genome alterations in COPD and lung cancer. This may lead to a better understanding of how lung cancer develops in patients with COPD.

Supported by the Mary Fuller Russell Fund

Update: The Sears lab has made progress in this research. Both our DNA repair proficient and deficient mice have completed the prolonged cigarette smoke exposures and mechanistic investigations into the impact of the DNA repair protein Xeroderma Pigmentosum Group C (XPC) on the lung cancer/emphysema overlap are ongoing. In the coming year we will complete spatial transcriptomics of the lungs, a technique that provides information about gene expression patterns within intact tissues. By studying the critical interactions involved in lung cancer development in those suffering from COPD, it is likely that both diseases, particularly the mechanistic link between the two, will be better understood and increase the likelihood of translating findings to human disease. Our ultimate goal is to use findings from this research to identify diagnostic and therapeutic targets for lung cancer and COPD.