My long-term research focus has been the development of gene therapies for cystic fibrosis (CF) lung disease. To achieve this, my research has centered on virology and recombinant viral vectors, specifically the dissection of recombinant adeno-associated virus (rAAV) transduction biology in human airway epithelium in vitro culture models and ferret lung airways in vivo. I have also investigated the infection mechanisms of a respiratory virus, human bocavirus 1 (HBoV1) in airway epithelium and worked on developing efficient airway transduction vectors and novel gene-editing approaches for CF gene therapy. My studies have led to several significant advances, such as the use of pharmaceutic intervention like proteasome inhibitors to enhance parvoviral vector intracellular trafficking for productive transduction in airway epithelium, as well as the development of dual-AAV trans-splicing approach and a chimeric rAAV/HBoV1 vector. Since the development of gene therapies requires testing in animal models that closely recapitulate human disease phenotype, a second major area of my research has been the development of CF ferret models. I played a critical role in creating CF ferret models with CFTR gene disrupted (knock-out) and mutation knock-in (F508del and G551D), as well as the model systems capable of conditional disrupting or reactivating CFTR expression. I also involved in the generation of the ROSA^mTmG CRE recombinase (Cre)-responsive reporter ferret line, along with several Cre-driver lines for cell lineage tracing. We are using these ferret model systems to identify target cells for effective CF lung gene therapy, and to illustrate the mechanisms of CF pathogenesis on cell-type specific base.