Scientists at Johns Hopkins are working to understand the basic biology of cystic fibrosis (CF). Gaining a better understanding of how changes in the cystic fibrosis transmembrane conductance regulator (CFTR) gene create the symptoms of CF will help to reveal targets for drug and genetic therapies.
The CFTR Gene and the Genetics of Cystic Fibrosis
Cystic fibrosis is caused by mutations in the CFTR gene, which is highly regulated in a tissue-specific manner. Dr. Garry Cutting is at the forefront of understanding the relationship between mutations in the CFTR gene and clinical symptoms. His laboratory has identified many of the unusual mutations in the CFTR gene that cause CF. Dr. Cutting directs a nationwide research project that is studying twins and siblings with CF to discover genes that may alter the progression of CF symptoms. Dr. J. Michael Collaco has focused on identifying other genes and environmental factors that affect the severity of CF lung disease. Dr. Scott Blackman is investigating influences on the development of CF-related diabetes (CFRD).
Dr. Cutting been studying the function of rare CFTR mutations and working to identify the effectiveness of currently available and novel therapeutics for these mutations. He has been instrumental in the creation of the CFTR2 database, which categorizes the functional consequences of CFTR mutations.
Elucidating the function of the CFTR protein, its interactions with other components of the cell and how CFTR is processed, is vitally important to our understanding of CF. This work is being undertaken by the laboratory of Dr. William Guggino. Dr. Liudmila Cebotaru‘s laboratory focuses on the effect of rare mutations on CFTR function.
Gene Therapy and Drug Delivery
Johns Hopkins researchers have pioneered the creation of adeno-associated virus (AAV) gene therapy vectors and their introduction into clinical trials. Ongoing research in the laboratories of Dr. William Guggino and Dr. Liudmila Cebotaru is aimed at unraveling the barriers to effective gene therapy and refining new vectors. Dr. Liudmila Cebotaru has been investigating the safety and effectiveness of newly created AAV vectors in animal models, key to creating a viable vector for human studies.
The laboratory of Dr. Justin Hanes focuses on novel nanoparticle technologies that can enable therapeutics delivery into the CF lung. His work has enhanced our understanding of the properties of CF mucus and challenges of drug and gene delivery into the CF lung.
Microbiology of the Cystic Fibrosis Airway
The emergence of resistant bacteria and their effect on the lung function of people with CF is being studied by Drs. Mark Jennings and Noah Lechtzin. Analysis of data collected in the CF Foundation registry is leading to a better understanding of the role of infection on the health of people with CF. Additionally, Dr. Jennings is developing therapies to eradicate methicillin resistant Staphylococcus aureus from the airways of individuals with CF. Dr. Kiera Cohen is studying the biology of non-tuberculous mycobacterium and approaches to treating infections these bacteria.
Mucociliary clearance or MCC is a major defense mechanism that protects the lungs from infection. Inhaled bacteria are trapped in the mucus that lines the airway and then transported out of the lungs by the beating of cilia, small hair-like structures on the surface of airway cells. The thick, sticky mucus that is present in the lungs of people with CF leads to abnormal MCC. Dr. Beth Laube is studying the role that MCC plays in the colonization of the CF airway. These studies are being performed in mouse models of CF as well as in individuals with CF.