Current Research and Scholarly Interests
I have participated in multiple clinical studies and have contributed to the development of therapeutic interventions designed specifically for the treatment of lung disease in children and adults with CF. Initially, my research interests concentrated on gene therapy for CF. Over time, the emphasis of my research led to investigator-initiated clinical research studies which have produced the description of novel mechanisms that drive the inflammatory milieu of the CF airway. With support from the CF Research Center resources at Stanford University, the CF Foundation, and the Food and Drug Administration, I have successfully completed Phase I and Phase IIa clinical research studies to assess the efficacy of N-acetylcysteine (NAC) in a novel approach to reduce inflammation in the lungs of CF patients. Building upon the foundation of these initial trials, and with CFF support, I completed a 3-years study, and was the Principal Investigator for a Phase II, multi-center trial for NAC in CF that began in November of 2008. The results of this study are published in the November issue of the Journal of Cystic Fibrosis.
As the pulmonary division has grown over the years, my clinical and academic interests have broadened to include pediatric lung transplantation. In 2002, I subsumed the role of program director for the pediatric pulmonary lung and heart-lung transplant program at LPCH. As a result, we are the 5th largest pediatric lung and heart-lung transplant program in the United States (the 2nd largest pediatric heart-lung transplant program) and the only pediatric lung transplant center in the Southwest, West, and Northwest region of the country (not including Texas). At least 100 infants and children have been evaluated at the center for pediatric lung and heart-lung transplantation at LPCH and 37 children have received transplants in this period of time.
My career plans are to foster further growth of the center with the goal to create a translational pediatric research center for lung and heart-lung transplantation at LPCH.
This nascent field of medicine is one in which little is known of the cellular and molecular mechanisms within transplantation dynamics and where the possibilities for discovery and therapeutic advances are considerable. In this field, I have co-authored several peer-reviewed manuscripts and abstracts, and I am a PI in international studies regarding outcomes for children who have undergone lung and heart-lung transplantation. The pediatric lung and heart-lung transplant program at LPCH is one of seven sites that participated in an international prospective study funded by the Clinical Trials in Organ Transplantation in Children (CTOT-C) from the NIH that will examine the effect that viral infections may have on the mechanisms of lung allograft rejection (development of bronchiolitis obliterans, OB) in children. OB is the single most important life-limiting process affecting lung and heart-lung transplant recipients. It is a fibrosing process that obliterates the allograft airway lumen. Once the process is initiated, it is difficult to abrogate. The etiology is poorly understood, and multifactorial. Most transplant researchers agree that ischemia-reperfusion injury (IRI) creates an abnormal cellular redox milieu that contributes to neutrophilic inflammation. Histopathologically, neutrophilic inflammation heralds the pathophysiologic consequences that result in graft failure due to OB. To date, the association of these early IRI and redox events to the occurrence of OB has not been fully investigated.
In 2014, the CTOT centers will proceed to an RDBPC study that will examine the effects of B-cell directed induction in combination with T-cell induction regimens on the effect of survival without BOS.