July 31, 2012

We recently had two more papers published.

Alicia Ballok, a Ph.D. student in the lab has published her second paper in as many weeks.  This study focuses on CifR, a transcriptional regulator of the secreted Cif toxin.  Cif, secreted in outer membrane vessicles, can enter a host cell and reduce expression of the CFTR ion channel by altering this protein's ubiquitination status.  Mutations in CFTR cause the genetic disease cystic fibrosis (CF).  We've worked on this protein for a number of years with other groups at Dartmouth, and this most recent effort was in collaboration with Chris Bahl and Dean Madden in Biochemistry.

A second publication, co-authored by Ed Griffin, a former technician who has headed off to graduate school, examines the susceptibility of P. aeruginosa biofilms grown on airway cells to a front-line CF antibiotic called Cayston.  The punchline is that only ~50% of clinical isolates of P. aeruginosa showed significant sensitivity to this antibiotic when grown under these conditions.  This work was headed by Qianru "Ru" Yu, a post-doc in Dr. Bruce Stanton's lab.  This work was funded in part by Novartis and the CF Foundation.

July 26, 2012

In collaboration with our colleagues in the Dartmouth Lung Biology Center, we recently published a paper titled "Does the dF508-CFTR Mutation Induce a Pro-inflammatory Response in Human Airway Epithelial Cells?", which you can link to here.  Alicia Ballok, a Ph.D. student in the lab, was the second author on the paper and performed the microarray studies presented.  The manuscript describes studies assessing the impact of the important Cystic Fibrosis (CF) pathogen, Pseudomonas aeruginosa, on the inflammatory response of CF-derived airway cells.  This study is important because it is widely believed that the CF lung is pro-inflammatory.  As stated in the paper, the take home message of our manuscript is: "Taken together with other published studies our data demonstrate that there is no compelling evidence to support the view that mutations in CFTR induce a hyperinflammatory response in human airway epithelial cells in vivo."  This work challenges the current dogma in the field and will force us to rethink the conditions in the CF lung, and the response of these patients to P. aeruginosa infections.

July 25, 2012

We just published our first cystic fibrosis microbiome study in the Journal of Bacteriology. The study, led by Laura Filkins, a Ph.D. student in the lab showed that only ~50% of patients analyzed had P. aeruginosa as the prominent pathogen, in contrast with current dogma.  She also identified, a number of Streptococci species present in these patient samples.  This work will form the basis of ongoing studies in this patient population, and represents a team effort among basic scientists, physician-scientists and a top notch statistician.