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

 描述(申请人提供)：候选人Meghan F.Davis，DVM公共卫生硕士博士，渴望从事一项独立的、由NIH资助的研究生涯，评估动物来源的微生物暴露对人类健康影响的影响。对于她提议的SERCA K01奖，她将首先调查动物细菌对儿童细菌的贡献(目标1)，然后将细菌 在患有哮喘的市中心城市儿童中，从微生物失调到疾病恶化(目标2)沿着以下途径进行：虫害和宠物微生物区系--儿童微生物区系-儿童呼吸道健康。她还将通过评估金黄色葡萄球菌来验证她的假设，即个别病原体也会导致哮喘发病率上升。金黄色葡萄球菌是一种已知会通过过敏机制恶化特应性湿疹的领先候选细菌，她还将建立一个生物检索库，通过未来的研究工作来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修改的致病细菌驱动因素，特别是与患有哮喘的低收入城市儿童有关的致病因素，这一群体的疾病负担不成比例。对于Davis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，并通过拨款、出版物和演讲提高科学声誉。主要导师、约翰霍普金斯医学院(JHSOM)副教授伊丽莎白·松井博士是一位过敏症专家和临床流行病学家，在指导K-Grant获奖者和NIH赞助的呼吸系统疾病环境决定因素研究方面有着出色的记录。JHSOM助理教授Meredith McCormack博士在哮喘目标疾病方面提供补充专业知识。其他科学咨询委员会成员将在微生物组和全基因组测序技术(Marsha Wills-Karp博士和Karen Carroll博士，宾夕法尼亚大学的外部导师Elizabeth Grice博士的帮助下)、生物信息学数据处理(Grice博士和Kasper Hansen博士)以及统计分析资源和培训(Hansen博士和Roger Peng博士)方面提供协助。这个多学科团队还将支持戴维斯博士在单一健康背景下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、Carroll博士和Kathen Gabrielson博士)的合作努力。作为一个整体，这个研究和培训平台将使Davis博士成为约翰霍普金斯大学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。这种支持性的制度环境包括最先进的基因组学核心设施、计算和数据资源，以及通过医学院进行的特殊临床研究计划。约翰霍普金斯大学的环境还为肺部医学、过敏和免疫学、比较医学和生物统计学方面的知名研究人员提供了途径。通过SERCA K01奖项，Meghan Davis博士将把她在暴露评估方面的兽医临床背景和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结合起来，成为与动物来源的复杂微生物暴露相关的人类呼吸道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.