Molecular determinants of small airway obstruction in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and attributes to increased health care costs in Canada due to its prevalence and a lack of disease-modifying therapies. COPD is characterized by irreversible lung function decline that is caused by destruction of lung elastic tissue and obstruction of the small airways, which allow airflow in and out of the lungs. In COPD, these lesions are produced in response to repetitive inhalational injury inflicted by smoke exposure but the mechanisms are unknown. Dr. Hackett and colleagues recently performed an in silico drug screen, and identified the tripeptide Gly-His-Lys (GHK) as a modulator of lung tissue destruction in COPD.

In her research program, Dr. Hackett will conduct a series of preclinical studies to evaluate GHK as a potential novel daily-use inhaled COPD therapy. The aim is to progress the drug toward FDA- investigational new drug approval.

To understand the molecular determinants of COPD, Dr. Hackett will first use novel micro x-ray computed imaging to determine how small airways are lost in patients with COPD. Secondly, using lung cells derived from patients with COPD she will determine which cells are the primary cells involved in small airway obstruction, and if GHK can modify these defective cells. Thirdly, Dr. Hackett will conduct pre-clinical studies of GHK to determine if it a therapeutic for COPD.

Dr. Hackett trusts that by pinpointing the causal determinants of COPD pathogenesis, these can be modulated to improve the treatment of this common and deadly disease.