Upper Airway Microbial Development During the First Year of Life

项目总结

PROJECT SUMMARY Dr. Kloepfer joined Indiana University School of Medicine (IUSM) as an assistant professor of Pediatrics as a tenure-track research scientist. Shortly after joining the IUSM faculty, she was awarded the departmental K12 Child Health Research Career Development Award from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. During her time on the K12, she has: 1) compiled a four member panel to provide mentorship as she works towards independence; 2) established a relationship with IUSM Obstetrics department to recruit from two campus hospitals and multiple outpatient clinics; 3) obtained IRB approval for the proposed study; 4) developed her lab in the Translational Research and Integrated Biology Lab (TRIB) facility housed within the Children’s Clinical Research Center (CCRC); 5) hired a clinical study coordinator and laboratory technician ; 6) established a collaboration with Dr. Douglas Rusch, an informatics expert in the Center for Genomics and Bioinformatics (CGB), an Indiana Clinical and Translational Sciences Institute (ICTSI) core; 7) successfully recruited 63 newborns for the proposed study; and 8) presented abstracts detailing preliminary data included in the attached proposal at the May 2015 and 2016 American Thoracic Society (ATS) meeting. During fellowship, Dr. Kloepfer became interested in the influence of airway bacteria on airway development. Dr. Kloepfer’s preliminary data demonstrates that decreased bacterial diversity in the airway at three months of age is associated with increased expression of IL-33 and IL-5, and wheeze by six months of age, suggesting that decreased bacterial diversity, cytokine changes and lung function changes occur prior to 3 months of age. 16S rRNA sequencing has not been utilized to prospectively follow newborns with sampling starting at birth. Because the prevalence of asthma continues to increase every year (currently 10% of the population), the etiology of asthma development needs further delineation, particularly in the developing airway prior to an asthma diagnosis. Therefore, to address the above questions, the attached proposal is designed to investigate if airway dysbiosis precedes, coincides with, or follows changes in airway cytokines and lung function in children who develop wheeze. This project was developed to align with Dr. Kloepfer’s long-term research goals. They include: determining how bacterial metabolites produced from the bacteria identified in the attached study cause airway inflammation; and translating this research into clinically relevant prevention and intervention strategies for children who develop recurrent wheeze and asthma. As we enter the era of personalized medicine, the influence of bacteria on immune development and airway function must be elucidated before methods of prevention and treatment can be prescribed and/or designed.