Shah Saddad Hussain, PhD

Chronic obstructive pulmonary disease (COPD), primarily caused by smoking, leads to progressive lung dysfunction. It is worsened by a genetic risk factor alpha-1-antitrypsin (AAT) deficiency. Obstruction of airways seen in COPD is due to structural changes, including the narrowing and loss of small airways, potentially associated with mucus plugging. AAT deficiency is a genetic risk factor that intensifies COPD severity. It leads to emphysema through lung tissue damage, accelerated by smoking. To understand the progression of COPD, we have developed an innovative COPD model in ferrets that allows us to measure airway loss and mucus obstruction, key factors that cause the disease. Our research focus is airway loss in COPD ferrets, determining whether mucus obstruction causes loss to occur, and identifying RNA signatures preceding airway remodeling and loss. This distinctive model promises to shed light on AAT deficiency's influence on COPD and inform the creation of new treatments.

Update: Our research focuses on understanding the mechanisms driving small airway loss—or "airway dropout"— a defining feature of early chronic obstructive pulmonary disease (COPD). Using advanced imaging and molecular analysis in a ferret model, we are tracking the loss of terminal small airways (bronchioles) and identifying cellular mechanisms—such as mucus obstruction and airway remodeling (abnormal changes in the cells lining the airways)—that drive this process. Preliminary data show a strong link between mucus accumulation and airway loss, offering new insight into early disease progression. These findings could pave the way for targeted therapies to preserve small airways and lung function in at-risk individuals who have COPD and who smoke.