Effects of the Intestinal Microbiota on Infections During Bone Marrow Transplant

描述（由申请人提供）：候选人，英陶尔博士，在纪念斯隆-凯特琳癌症中心的传染病讲师，旨在实现作为一个在传染病领域的临床研究人员的学术生涯。该项目提出了一个五年计划，在埃里克·帕默和肯特·塞普科维茨博士的指导下，他可以采取措施成为一名独立的医生科学家。本项目旨在研究异基因造血干细胞移植（HSCT）患者肠道植物群，并确定植物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HSCT的患者中连续采集粪便样本来完成。使用高通量测序方法，分析每份粪便样本，以表征微生物组成。将计算各种微生物生态学指标，并用于描述肠道植物群。将与VRE菌血症和CDAD的风险进行相关性研究。该项目的具体目的如下：（1）描述HSCT期间发生的肠道植物群变化，（2）识别引起VRE菌血症风险的肠道植物群特征，（3）识别引起CDAD风险的肠道植物群特征。该项目将能够确定肠道植物群的“关键参与者”，其存在或不存在在感染的发展中起着至关重要的作用。有了对肠道植物群和感染性疾病之间病因学关系的透彻理解，就有可能设计出明智的策略，以明确的方式预防、诊断或治疗这些感染。在整个五年期间，候选人将定期与他的导师会面，与MSKCC的其他相关专家互动，并通过结构化会议，会议和课程来补充他的培训。在提案期结束时，他将能够获得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.