Clinical Research Programs

Damage from chronic lung infections and inflammation are a persistent problem for CF patients, and over the long run, patients develop a deficit in total body anti-oxidant quantity of glutathione. This situation creates a vicious cycle of inflammation, infection and ongoing damage to the lungs, because patients do not have enough glutathione to help calm the inflammation. N-acetylcysteine (aka, NAC), is a nutritional supplement that is a precursor of the body’s primary anti-oxidant protein, called glutathione. NAC has been used successfully in treating a number of diseases including HIV/AIDS and COPD in adults. Dr. Conrad designed and carried out a 3-year, multi-center, placebo-controlled trial that measured the safety and efficacy of high dose, oral NAC in CF patients. (2008- 2011). J Cyst Fibros. 2015 Mar;14(2):219-27 PMID: 25228446. The patients took NAC 3 times a day for 6 months. Results of the study demonstrate that NAC treatment may help to preserve lung function in children and adults with CF. More 

Since then, Dr. Conrad has focused on research focused in the pediatric lung transplant population.  In 2011, through a funding mechanism for Clinical Trials in Organ Transplantation in Children (CTOTC) sponsored by the National Institutes of Health (NIH). Dr. Conrad as co-investigator, has participated in several studies in this population. The first, in 2011, was a non-randomized observational study to determine whether respiratory viral infections increase the risk of bronchiolitis obliterans syndrome, obliterative bronchiolitis, death or retransplantation in pediatric lung transplant recipients. The study is ongoing, though Dr. Conrad initiated a sub-study in 2013 to assess whether a cytokine biomarker could be discerned from serial measures of the bronchoalveolar lavage fluid obtained from the study participants.  Analysis is ongoing.

Currently, the LPCH Pediatric Lung Transplant Program is participating in the most recent CTOT multi-center clinical study sponsored by the NIH.  The primary study objective is to determine the effects of rituximab induction on post-transplant immunity in pediatric lung transplant recipients.  This study is ongoing.

Dr. Conrad is also interested in assessing the power of next-generation sequencing techniques to study the airway epithelial response to ischemia and reperfusion injury at the time of transplant, and how that may affect and initiate chronic lung graft dysfunction.

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My research interests have centered on the inflammatory responses that lead to airway disease in Cystic Fibrosis (CF) and the metabolic factors that contribute to CF lung disease progression. Current efforts are focused on the understanding of the early events that drive the development of lung disease through the study of infants with CF identified by newborn screening. This includes the development of new diagnostic tools that permit the early detection of lung disease manifestations.

Dr. Moss has conducted bench, translational and clinical research since the mid-1980’s. He headed the pediatric pulmonary research group from 1991 to 2006 and joined the first cohort of the Cystic Fibrosis Foundation’s Therapeutics Development Network in 1998, where he was the first chair of its protocol review committee. Dr Moss directed the Ross Mosier Laboratory for CF Research at Stanford for 25 years until 2005. He was initial Co-Director of Stanford’s Children’s Health Research Program; with Stanford’s Clinical and Translational Science Award award from the National Institutes of Health he became a member of the Spectrum Child Health Executive Committee. Dr. Moss was director of the Stanford allergy-immunology and pediatric pulmonology fellowship training programs, and was Chief of both these divisions in the Department of Pediatrics at Stanford. Currently he is a member of the Stanford Pediatrics Mentoring Group, supporting trainees and faculty in career development, and is a member of the Stanford University School of Medicine human subjects Institutional Review Board. Dr. Moss’ 230+ publications have garnered over 10,000 citations in the peer-review biomedical literature. His research in recent years has focused on novel therapeutics and outcome measures in cystic fibrosis (CF), and allergic fungal lung disease with internationally recognized expertise in allergic bronchopulmonary aspergillosis (ABPA). More 

Dr. Moss’ early research focused on issues in adaptive immune responses, primarily in two settings: chronic lung infection in cystic fibrosis, and natural and therapeutic responses to allergens in atopic asthma. He was one of the first investigators to point to chronic inflammation as a critical component of CF and identify biomarkers of progression. He investigated allergic drug responses and described one of the first drug desensitization approaches in CF. He described immune responses to allergen immunotherapy and chronic infection with a focus on induction of blocking antibodies. In the 1990’s he became increasingly interested in T cell responses in CF. His group described CFTR expression in lymphocytes, cloned T cells for ex vivo study, and described lymphocyte cytokine dysregulation. Dr. Moss posited CF (before the discovery and description of T17 and Treg subsets) as a Th2 immune deviation disease. With the advent of specific CF therapeutics in the early 2000’s he became involved in many translational clinical trials including gene therapy, cytokine immunomodulators, biologics, and small molecules including the first study to show CFTR modulation by the potentiator ivacaftor.

With Professor William Northway, who first described bronchopulmonary dysplasia (BPD), Dr. Moss characterized the long-term outcome of BPD.

More recently Dr. Moss has become interested in fungal immunomodulation, polymicrobial lung infection, and the problems of allergic fungal lung disease. In collaboration with the laboratory of Len and Lee Herzenberg at Stanford he developed a new diagnostic test for allergic bronchopulmonary aspergillosis based on the flow cytometric basophil activation test, and he is currently pursuing new therapies for fungal lung disease.

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