Effects of pest and pet animal microbiota on child microbiota and asthma: a one health study

 描述（由申请人提供）：候选人梅根F。戴维斯，DVM MPH博士，渴望一个独立的，NIH资助的研究事业，评估动物源性微生物暴露对人类健康影响的影响。对于她提出的SERCA K 01奖，她首先将调查动物细菌对儿童细菌的贡献（目标1），然后将细菌与儿童细菌联系起来。 在患有哮喘的内城城市儿童中（目标2），沿着以下途径从生态失调到疾病恶化：害虫和宠物微生物群->儿童微生物群->儿童呼吸系统健康。她还将通过评估S.金黄色葡萄球菌，一种已知通过过敏机制使特应性湿疹恶化的主要候选细菌，并通过建立生物标本库来通过未来的研究工作调查其他候选病原体。哮喘影响着美国近700万儿童，这项工作旨在确定新的和可改变的致病细菌驱动因素，特别是与低收入城市哮喘儿童相关的致病细菌驱动因素，这些儿童的疾病负担不成比例。对于戴维斯博士来说，这项工作和随之而来的职业发展计划还将提供人类临床研究，细菌测序和大数据分析方面的关键培训，并保护时间，以建立高质量的独立研究计划，并通过赠款，出版物和演讲来提高科学声誉。主要导师Elizabeth Matsui博士是约翰霍普金斯医学院（JHSOM）的副教授，是一位过敏症专家和临床流行病学家，在指导K补助金获得者和NIH赞助的呼吸道疾病环境决定因素研究方面有着出色的记录。Meredith McCormack博士，JHSOM的助理教授，提供哮喘目标疾病的补充专业知识。其他科学咨询委员会成员将协助微生物组和全基因组测序技术（玛莎·威尔斯-卡普和凯伦·卡罗尔博士，以及宾夕法尼亚大学的外部导师伊丽莎白·格莱斯博士），生物信息学数据处理（格莱斯和卡斯珀汉森博士）以及统计分析资源和培训（汉森和罗杰·彭博士）。这个多学科团队还将支持戴维斯博士在一个健康环境中的教师发展和领导能力，并扩大她与比较医学教师（Wills-Karp博士、卡罗尔和凯瑟琳·加布里尔森）的合作。总的来说，这个研究和培训平台将使戴维斯博士成为约翰霍普金斯彭博公共卫生学院环境健康科学系的独立研究员和助理教授。这种支持性的机构环境包括最先进的基因组学核心设施，计算和数据资源，以及通过医学院的特殊临床研究计划。约翰霍普金斯的环境还提供了访问著名的研究人员在肺医学，过敏和免疫学，比较医学和生物统计学。通过SERCA K 01奖，Meghan Davis博士将她的兽医临床背景和暴露评估方面的博士培训与生物信息学，临床流行病学和人类哮喘方面的新技能相结合，成为与动物源性复杂微生物暴露相关的人类呼吸系统健康影响的独立研究人员和专家。

 DESCRIPTION (provided by applicant): Candidate Meghan F. Davis, DVM MPH PhD, aspires to an independent, NIH-funded research career evaluating the impacts of microbial exposures of animal origin on health effects in people. For her proposed SERCA K01 award, she first will investigate the contributions of animal bacteria to child bacteria (aim 1), and then link bacterial dysbiosis to exacerbations of disease among inner-city urban children with existing asthma (aim 2) along the following pathway: pest and pet microbiota->child microbiota->child respiratory health. She also will test her hypothesis that individual pathogens also drive asthma morbidity by evaluating S. aureus, a leading candidate bacterium known to worsen atopic eczema through allergic mechanisms, and by establishing a biospecimen repository to investigate other candidate pathogens through future research efforts. Asthma affects almost seven million children in the United States, and this work is positioned to identify novel and modifiable bacterial drivers of morbidity particularly relevant to low-income urban children with asthma, a population with a disproportionate burden of disease. For Dr. Davis, this work and attendant career development program also will provide critical training in human clinical research, bacterial sequencing and big data analysis, and protected time to establish a high-quality independent research program and grow a scientific reputation through grants, publications, and presentations. Primary mentor Dr. Elizabeth Matsui, Associate Professor at the Johns Hopkins School of Medicine (JHSOM), is an allergist and clinical epidemiologist with an outstanding track record of mentorship of K-grant awardees and NIH-sponsored research on the environmental determinants of respiratory disease. Dr. Meredith McCormack, Assistant Professor at JHSOM, provides complementary expertise in the target disease of asthma. Other scientific advisory committee members will assist with microbiome and whole genome sequencing techniques (Drs. Marsha Wills-Karp and Karen Carroll, with external mentor Dr. Elizabeth Grice at the University of Pennsylvania), bioinformatics data processing (Drs. Grice and Kasper Hansen), and statistical analysis resources and training (Drs. Hansen and Roger Peng). This multidisciplinary team also will support Dr. Davis' faculty development and leadership in a one health context and expand her collaborative efforts with faculty in Comparative Medicine (Drs. Wills-Karp, Carroll and Kathleen Gabrielson). Taken as a whole, this research and training platform will position Dr. Davis to succeed as an independent researcher and Assistant Professor in the Department of Environmental Health Sciences at Johns Hopkins Bloomberg School of Public Health. This supportive institutional environment includes a state-of-the-art genomics core facility, computing and data resources, and an exceptional clinical research program through the School of Medicine. The Johns Hopkins environment also provides access to prominent investigators in pulmonary medicine, allergy and immunology, comparative medicine, and biostatistics. Through a SERCA K01 award, Dr. Meghan Davis will synergize her veterinary clinical background and PhD training in exposure assessment with new skills in bioinformatics, clinical epidemiology and human asthma, emerging as an independent researcher and expert on the human respiratory health effects related to complex microbial exposures of animal origin.