Effects of the Intestinal Microbiota on Infections During Bone Marrow Transplant

应聘者描述(申请人提供)：应聘者英陶尔博士，纪念斯隆-凯特琳癌症中心传染病讲师，寻求成为传染病领域的临床研究人员的学术生涯。这个项目提出了一个五年计划，在这个计划中，他可以在Eric Pamer博士和Kent Sepkowitz博士的指导下，采取措施成为一名独立的内科科学家。该项目旨在研究异基因造血干细胞移植(HSCT)患者的肠道菌群，并确定菌群与两种感染风险的关系，即万古霉素耐药肠球菌(VRE)菌血症和艰难梭菌相关性腹泻(CDAD)。这将通过从接受造血干细胞移植的患者身上连续收集粪便样本来完成。使用高通量测序方法，将对每个粪便样本进行分析，以确定微生物组成。各种微生物生态指标将被计算并用于描述肠道菌群。将与VRE菌血症和CDAD的风险相关联。该项目的具体目标如下：(1)确定HSCT期间发生的肠道菌群变化的特征；(2)确定导致VRE菌血症风险的肠道菌群；(3)确定导致CDAD风险的肠道菌群。该项目将能够确定肠道菌群的“关键角色”，它们的存在或不存在在感染的发展中起着至关重要的作用。对肠道菌群和传染病之间的病原学关系有了透彻的了解，就有可能设计出智能策略来以确定的方式预防、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，并通过有组织的会议、会议和课程来补充他的培训。在建议期结束后，他将能够获得传染病临床研究员的独立身份。

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.