Immune profiling to stratify Clostridioides difficile infection outcomes

通过免疫分析对艰难梭菌感染结果进行分层

• 批准号: 10449357
• 负责人: Gregory Russell Madden
• 金额: $ 19.22万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-12 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10449357
• 关键词: Antibiotic Resistance; Antibodies; Arizona; Award; Biological Markers; Biometry; Blood; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinical; Clinical Data; Clinical Markers; Clinical Research; Clinical Trials Design; Clostridium difficile; Colectomy; Colorectal Surgery; Communicable Diseases; Data; Data Science; Databases; Development Plans; Diagnosis; Diagnostic; Disease; Doctor of Philosophy; Enteral; Environment; Epidemiologist; Epidemiology; Feces; Funding; Goals; Health Sciences; Healthcare; Hospital Mortality; Hospitals; Host Defense; IL8 gene; Immune; Immune system; Immunity; Immunologic Markers; Immunologics; Immunology; Infection; Innate Immune System; Institutes; Institution; Interleukin-15; Interleukin-6; K-Series Research Career Programs; Lead; Life; Literature; Machine Learning; Master' s Degree; Measures; Mediating; Medical; Mentors; Metadata; Methods; Michigan; Modeling; Molecular; National Institute of Allergy and Infectious Disease; Operative Surgical Procedures; Organism; Outcome; Pathogenesis; Pathogenicity; Patients; Performance; Play; Predictive Analytics; Public Health Schools; RANTES; Research; Research Personnel; Resources; Risk; Risk Assessment; Risk Factors; Role; Schools; Science; Sepsis; Serum; Standardization; Statistical Models; System; TNF gene; Techniques; Testing; Therapeutic; Time; Toxin; Training Activity; Universities; Virginia; Work; adverse outcome; antitoxin; base; biobank; career development; cytokine; eosinophil; experience; fecal transplantation; healthcare-associated infections; innovation; microbiome; molecular diagnostics; mortality; novel; novel marker; novel therapeutics; outcome prediction; pathogen; precision medicine; predictive modeling; professor; prospective; receptor; response; risk stratification; specific biomarkers; stool sample; translational scientist

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.

Gregory Madden博士是弗吉尼亚大学传染病学助理教授