Stanford University
Nam Soo Joo, Ph.D., Senior Research Scientist, CF Translational Research, Pediatric pulmonology/School of Medicine/Stanford University.
I have been working in CF research field with a special emphasis on a potential role played by airway submucosal glands in the process of CF lung disease since I joined the cystic fibrosis research laboratory, directed by Dr. Jeffrey J. Wine, at Stanford in 1999. Since then, I have contributed to the development of important methods in collaboration with colleagues at Stanford: an in situ optical gland secretion assay for measuring fluid secretion rates and compositions from individual airway submucosal glands; a bioluminescence assay for bacterial killing with saliva samples; proteomic assay of gland mucus from CF and control human airways; airway smooth muscle contraction assay & and mucociliary clearance (MCC) assay for measuring a mucociliary clearance velocity using ex vivo WT & CF animal tracheae. With these methodologies, we discovered defects in submucosal gland secretory functions in CF airways from human and CF animal models. Recently, we discovered synergistic MCC in ex vivo animal tracheae by combining β adrenergic and low dose cholinergic agonists (synergy agonists, SA), including CF ferrets without inducing airway narrowing. SA produced synergistic MCC in in vivo sheep model of CF airway. Outcome of preclinical clinical safety and tolerability trials in healthy and CF subjects indicated that SA is safe to use in humans. To better understand the underlying mechanisms of synergistic enhancement of MCC, experiments are underway: using ex vivo MCC assays-ENaC involvement; changes in airway surface liquid (ASL) height-synchrotron method; intracellular [Ca2+]i levels-ratiometric and GCaMP methods; viscoelasticity-dynamic light scattering microrheology assay; and in situ gland secretion assay with WT & CF animals. The outcome of these studies would provide important information necessary to develop SA as a potential therapeutic for patients with airway muco-obstructive disorders, including CF.
W02--Agnostic Avenues: Alternatives to CF Gene Therapy
Thursday, September 26, 2024
7:45 AM – 9:45 AM ET
Thursday, September 26, 2024
7:45 AM – 9:45 AM ET