Immune profiling to stratify Clostridioides difficile infection outcomes

候选人：格雷戈里·马登博士是弗吉尼亚大学传染病助理教授， 在诊断、流行病学和发病机制方面的研究经验。艰难感染 职业发展计划和目标：拟议的K23指导职业发展奖将独特地 确立了Madden博士作为一名具有宿主-病原体相互作用经验的翻译研究人员， 建模技术该奖项的培训活动包括临床试验设计的研究生课程 和统计建模，最终获得临床研究科学硕士学位。 研究计划：艰难梭菌是美国主要的医疗保健相关病原体。证据 提示宿主先天免疫系统（特别是2型或嗜酸性粒细胞介导的免疫）、粪便C. 艰难梭菌负荷和二元毒素在C.艰难感染然而，没有模型可以预测 C的结果。艰难梭菌感染考虑了这些因素。我们实验室的数据显示， 病原性免疫的特异性生物标志物（即，可溶性ST 2受体，IL-6），粪便微生物负荷，以及 粪便二元毒素的存在与C.艰难的死亡率Madden博士建议：1） 建立临床免疫学数据库。很难让患者开发出一种基于生物标志物的 C.结果模型艰难梭菌感染和2）Proximal验证了该模型以及领先的 临床模型这项研究的成功完成将为C. 艰难的感染结果，反映了我们对发病机制的最新理解。此外，我们将确定一个 研究人员和临床医生急需的最佳方法来分层危及生命的C。艰难感染. 诊断的时间。 导师：Madden博士的导师是William A. Petri，医学博士，博士，在宿主防御领域的领先研究员 针对C.很难内部顾问和合作者在医院流行病学方面具有不同的专业知识（Costi博士 Sifri，具有分子发病机制研究背景的执业医院流行病学家）， 免疫学（Melanie Rutkowsi博士，PhD），生物统计学/机器学习（Mr. Ma博士，PhD），临床试验设计 (Dr. James A. Platts-Mills，MD）和分子诊断学（Eric R. Houpt，MD）。 环境：弗吉尼亚大学以其在肠道疾病方面的工作而闻名于世，是最早的肠道疾病研究机构之一。 机构建立一个致力于数据科学的学校。弗吉尼亚大学数据科学研究所， 公共卫生科学学院、医院流行病学办公室和Petri实验室将提供资源 以及多样化和激励的环境，使这位候选人能够作为一名独立调查员蓬勃发展 在这个尖端领域。

Candidate: Dr. Gregory Madden is an Assistant Professor of Infectious Diseases at the University of Virginia with experience in research regarding the diagnosis, epidemiology, and pathogenesis of C. difficile infection. Career Development Plan and Goals: The proposed K23 Mentored Career Development Award will uniquely establish Dr. Madden as a translational researcher with experience in host-pathogen interactions and advanced modeling techniques. Training activities for the award include graduate-level coursework in clinical trial design and statistical modeling, culminating with a Master’s Degree of Science in Clinical Research. Research Plan: Clostridioides difficile is the leading healthcare-associated pathogen in the US. Evidence suggests that the host innate immune system (particularly Type 2, or eosinophil-mediated immunity), fecal C. difficile burden, and Binary toxin play important roles in C. difficile infection. However, no model to predict outcomes of C. difficile infection takes these factors into account. Data from our lab show that eosinopenia, specific biomarkers of pathogenic immunity (i.e., Soluble ST2 Receptor, IL-6), fecal organism burden, and the presence of fecal Binary Toxin are associated with increased C. difficile mortality. Dr. Madden, proposes to: 1) Construct a clinical-immunologic database of C. difficile patients to develop a robust biomarker-based model for outcomes of C. difficile infection and 2) Prospectively validate this model alongside the leading clinical models. Successful completion of the proposed research will create a validated immune profile for C. difficile infection outcomes that reflects our latest understanding of pathogenesis. In addition, we will identify a much-needed optimal approach for researchers and clinicians to stratify life-threatening C. difficile infection at the time of diagnosis. Mentors: Dr. Madden’s mentor is Dr. William A. Petri, MD, PhD, a leading researcher in the field of host defense against C. difficile. Internal advisors and collaborators have diverse expertise in hospital epidemiology (Dr. Costi Sifri, accomplished practicing hospital epidemiologist with a background studying molecular pathogenesis), immunology (Dr. Melanie Rutkowsi, PhD, biostatistics/machine learning (Jennie Ma, PhD), clinical trial design (Dr. James A. Platts-Mills, MD), and molecular diagnostics (Eric R. Houpt, MD). Environment: The University of Virginia is world-renowned for its work in enteric diseases and is one of the first institutions to establish a School dedicated to Data Science. The University of Virginia Data Science Institute, School of Public Health Sciences, Office of Hospital Epidemiology, and the Petri Lab will provide the resources as well as the diverse and stimulating environment for this Candidate to flourish as an independent investigator in this cutting-edge field.