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.

Public Health Relevance

This project examines the role of intestinal bacteria in the development of infections, in adults undergoing bone marrow transplantation. This research will help us to gain a better understanding of these infections, and in so doing, it will be possible to devise improved strategies to deal with them.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AI095398-04
Application #
8685103
Study Section
Microbiology and Infectious Diseases Research Committee (MID)
Program Officer
Prograis, Lawrence J
Project Start
2011-07-20
Project End
2016-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
City
New York
State
NY
Country
United States
Zip Code
10065
Lee, Yeon Joo; Arguello, Esther P; Jenq, Robert R et al. (2017) Protective Factors in the Intestinal Microbiome Against Clostridium difficile infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation. J Infect Dis :
Lee, Yeon Joo; Arguello, Esther S; Jenq, Robert R et al. (2017) Protective Factors in the Intestinal Microbiome Against Clostridium difficile Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation. J Infect Dis 215:1117-1123
Becattini, Simone; Littmann, Eric R; Carter, Rebecca A et al. (2017) Commensal microbes provide first line defense against Listeria monocytogenes infection. J Exp Med 214:1973-1989
Weber, Daniela; Jenq, Robert R; Peled, Jonathan U et al. (2017) Microbiota Disruption Induced by Early Use of Broad-Spectrum Antibiotics Is an Independent Risk Factor of Outcome after Allogeneic Stem Cell Transplantation. Biol Blood Marrow Transplant 23:845-852
Becattini, Simone; Taur, Ying; Pamer, Eric G (2016) Antibiotic-Induced Changes in the Intestinal Microbiota and Disease. Trends Mol Med 22:458-78
Taur, Ying (2016) Intestinal microbiome changes and stem cell transplantation: Lessons learned. Virulence 7:930-938
Taur, Ying; Pamer, Eric G (2016) Microbiome mediation of infections in the cancer setting. Genome Med 8:40
Buffie, Charlie G; Bucci, Vanni; Stein, Richard R et al. (2015) Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517:205-8
Taur, Ying; Jenq, Robert R; Ubeda, Carles et al. (2015) Role of intestinal microbiota in transplantation outcomes. Best Pract Res Clin Haematol 28:155-61
Jenq, Robert R; Taur, Ying; Devlin, Sean M et al. (2015) Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease. Biol Blood Marrow Transplant 21:1373-83

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