Upper Airway Microbial Development During the First Year of Life

项目总结 Kloepfer医生加入印第安纳大学医学院(IUSM)担任儿科学助理教授 作为终身教职研究科学家。在加入IUSM教职员工后不久，她被授予系 尤尼斯·肯尼迪·施莱弗国家健康研究所颁发的K12儿童健康研究职业发展奖 儿童健康与人类发展。在她参加K12期间，她：1)建立了一个四人小组 在她走向独立的过程中提供指导；2)与IUSM产科建立了关系 部门将从两家校园医院和多家门诊部招聘；3)获得IRB批准 建议的研究；4)在翻译研究和综合生物学实验室(TRIB)设施中开发她的实验室 在儿童临床研究中心(CCRC)内；5)聘请了临床研究协调员和 实验室技术员；与该中心的信息学专家道格拉斯·拉什博士建立了合作关系 基因组学和生物信息学(CGB)，印第安纳州临床和转化科学研究所(ICTSI)的核心； 7)为拟议的研究成功招募了63名新生儿；8)提交了摘要，详细说明了初步 2015年5月和2016年5月美国胸科学会(ATS)会议上所附提案中的数据。 在研究员期间，Kloepfer博士对呼吸道细菌对呼吸道的影响产生了兴趣 发展。Kloepfer博士的初步数据表明，在 3个月龄与IL-33和IL-5的表达增加有关，而6个月龄时会出现喘息 年龄，表明细菌多样性下降，细胞因子变化和肺功能变化发生在3岁之前 几个月大的孩子。16S rRNA测序还没有被用于前瞻性地对新生儿进行采样 从出生开始。因为哮喘的患病率每年都在持续增加(目前有10%的人 人群)，哮喘的病因学需要进一步描述，特别是在发展中的呼吸道。 在哮喘诊断之前。因此，为了解决上述问题，所附提案旨在 调查呼吸道生物失调是否先于、同时或跟随呼吸道细胞因子和肺功能的变化 患有喘息症的儿童。 这个项目的开发是为了与Kloepfer博士的长期研究目标保持一致。它们包括： 确定所附研究中确定的细菌产生的细菌代谢物如何引起呼吸道 炎症；并将这项研究转化为临床相关的预防和干预策略 反复出现喘息和哮喘的儿童。随着我们进入个性化医疗时代，影响 细菌对免疫发育和呼吸道功能的影响必须在预防和预防方法之前阐明 治疗可以是处方和/或设计的。

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.