Peter Miller, MD, PhD

Chronic obstructive pulmonary disease (COPD) is a common lung disease that causes extensive hospitalization and death. While age and smoking are major risk factors for COPD, there are other important contributors and the biological drivers of COPD remain incompletely understood. We will study how DNA mutations that occur in blood cells of individuals (termed clonal hematopoiesis, or CH) contribute to a variety of non-blood diseases. CH is quite common, occurring in more than 10% of individuals over the age of 60. We recently published a study showing that individuals with CH had a higher risk of having COPD, and then used laboratory models to confirm our findings. We will now study how other common forms of CH can contribute to COPD. We will be expanding our original study to include over 500,000 patients and use mouse models to dissect the underlying biology. We believe our work will identify at risk-populations and enable new therapies to prevent and treat COPD.

Update: We have made important progress in our first year of the grant. We have extended our analyses of large human cohorts to define the association between cigarette smoke exposure (CSE), clonal hematopoiesis (CH), and COPD. These data show that individuals with CSE have higher rates of CH, and those with CH have higher rates of COPD. We have utilized our mouse models to confirm that mice with clonal hematopoiesis have enhanced pulmonary emphysema after exposure to cigarette smoke.