Research is as the core of our mission as a Center for Excellence. The last two decades have witnessed dramatic changes in the biomedical sciences that have translated into substantial improvements in the diagnosis and care of children with cystic fibrosis. As palpable examples, survival with cystic fibrosis beyond childhood is now an expectation rather than an outcome observed only under a best case scenario, a significant proportion of new diagnosis are being made in the first few weeks of life providing an excellent opportunity for early intervention, and novel therapies targeting the main defect are for the first time accessible to patients. This remarkable progress in spite of the absence yet of a definitive cure for CF is the result of the combination of a number of factors starting with the presence of a strong and focused research enterprise. As a result, research to further our understanding of the pathophysiologic processes underpinning CF that also point towards targets for therapeutic intervention continues to advance at an accelerated pace. We are proud of our active involvement in these efforts and remain fully committed to continue to advance the science of CF. Perhaps as importantly, clinical therapeutic research at the Stanford CF Center is now conducted within a well-coordinated and focused program that has brought together a large cadre of excellent investigators. An integral component of our program is the Ross Mosier CF Research Laboratory. The mission of the laboratory is to provide to investigators the resources and means for the rapid translation of scientific advances.
Established thanks to generous support received over three decades form the Mosier Golf Classic (www.rossmosierclassic.org), the laboratory has maintained a high activity level and visible productivity that has included high impact publications and presentations. We are fortunate to have in place a highly interactive community of basic and clinical scientists that have produced a unique environment at Stanford. Further, our efforts are not in a vacuum. Stanford University at large has embraced the concept of clinical translational research and provides an environment that is fully supportive of our efforts. By engaging our colleagues from across disciplines in the basic sciences, clinical sciences, and bioinformatics fields at Stanford, we have established a most successful collaborative, cohesive effort in pediatric pulmonary translational research in California. Our strong Institutional support and, as importantly, the support from our patients, families and community at large, provides to us the impetus to continue with our discovery work. As an example, our translational CF research program has demonstrated strong leadership in clinical trials design and conduct, novel outcomes measurements development, identification of novel targets for CF therapeutics, and training the future generations of CF investigators and research team members.
As basic and translational pulmonary research continue to evolve, and new potential therapies are identified, current efforts of investigators at the laboratory are focused on the following areas:
1. FACS based assessment of cell populations in sputum and peripheral blood to identify biomarkers of lung disease activity. This has been a strong focus of Dr Richard Moss who has identified blood circulating basophil responses as a biomarker for Allergic Bronchopulmonary Aspergillosis (ABPA), with recent publications on its validation.
2. Biomarker discovery through profiling of the CF metabolome. We continue an active collaboration with the Stanford Mass Spectrometry facility and have recently focused on the development of novel platforms for the assessment of elastin degradation products in urine.
3. Sweat rate as a biomarker for CFTR activity. In collaboration with Dr Jeff Wine’s laboratory we have ongoing studies to further refine the methodology, with recent presentation at NACF on our direct quantitative methodology.
4. Studies of small metabolite profiling of salivary gland mucus secretions to identify novel biomarkers of CFTR activity. This work is in part funded by CFRI and aims to develop and validate practical methodology for fast and accurate assessment of CFTR function at the individual level.
5. Use of high-throughput technologies for the assessment of the airway microbiome. Thanks to our ongoing collaboration with the Quake lab at Stanford (one of the premiere laboratories in the world for advances in sequencing technology) we continue to advance studies of the dynamics of microbiome profiles surrounding exacerbations in CF.
7. Studies to better define genotype-phenotype associations and outcome prediction in newborns identified by CF screening. Dr Milla is also a participant of the recently convened diagnostic consensus panel convened by the CFF.