Effects of the Intestinal Microbiota on Infections During Bone Marrow Transplant

简介（由申请人提供）：候选人Ying Taur博士是纪念斯隆-凯特琳癌症中心的传染病讲师，希望在传染病领域实现临床研究的学术生涯。这个项目提出了一个五年计划，在此期间，他可以采取步骤，在博士的指导下成为一名独立的内科科学家。Eric Pamer和Kent Sepkowitz。本项目旨在研究同种异体造血干细胞移植（HSCT）患者的肠道菌群，确定菌群与万古霉素耐药肠球菌（VRE）菌血症和艰难梭菌相关性腹泻（CDAD）两种感染风险之间的关系。这将通过从接受造血干细胞移植的患者连续收集粪便样本来完成。使用高通量测序方法，每个粪便样本将进行分析，以表征微生物组成。各种微生物生态学措施将被计算和用于描述肠道菌群。将与VRE菌血症和CDAD风险进行相关性分析。该项目的具体目标如下：(1)表征HSCT期间肠道菌群的变化；(2)确定与VRE菌血症风险相关的肠道菌群特征；(3)确定与CDAD风险相关的肠道菌群特征。该项目将能够确定肠道菌群的“关键参与者”，它们的存在或缺失在感染的发展中起着至关重要的作用。有了对肠道菌群和传染病之间病原学关系的透彻理解，就有可能设计出智能策略，以明确的方式预防、诊断或治疗这些感染。在整个五年期间，候选人将与他的导师定期会面，与MSKCC的其他相关专家互动，并通过结构化的会议、会议和课程来补充他的培训。在提案期结束时，他将能够实现传染病临床研究员的独立地位。

DESCRIPTION (provided by applicant): The candidate, Dr. Ying Taur, an infectious diseases instructor at Memorial Sloan-Kettering Cancer Center, seeks to achieve an academic career as a clinical researcher in the field of infectious diseases. This project proposes a five-year plan where he can take steps to become an independent physician-scientist, under the mentorship of Drs. Eric Pamer and Kent Sepkowitz. This project seeks to study the intestinal flora of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), and determine the relationship between flora and the risk for two infections, bacteremia with vancomycin-resistant Enterococcus (VRE) and Clostridium difficile-associated diarrhea (CDAD). This will be done by collecting stool samples serially from patients undergoing HSCT. Using high-throughput sequencing methods, each stool sample will be analyzed in order to characterize the microbial composition. A variety of microbial ecology measures will be calculated and used to describe the intestinal flora. Correlations will be made with risk of VRE bacteremia and CDAD. The specific aims of the project are as follows: (1) Characterize the changes in intestinal flora that occur during HSCT, (2) Identify intestinal flora profiles that impart risk for VRE bacteremia, (3) Identify intestinal flora profiles that impart risk for CDAD. This project will be able to identify the "key players" of the gut flora, whose presence or absence play an essential role in the development of infection. Armed with a thorough understanding of the etiologic relationship between the gut flora and infectious diseases, it will be possible to design intelligent strategies to prevent, diagnose, or treat these infections in a definitive manner. Throughout the five-year period, the candidate will meet regularly with his mentors, interact with other pertinent experts at MSKCC, and supplement his training with structured meetings, conferences, and coursework. At the end of the proposal period, he will be able to achieve independent status as a clinical researcher in infectious diseases.