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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Mentored Patient-Oriented Research Career Development Award (K23)
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Microbiology and Infectious Diseases Research Committee (MID)
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Prograis, Lawrence J
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New York
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Becattini, Simone; Taur, Ying; Pamer, Eric G (2016) Antibiotic-Induced Changes in the Intestinal Microbiota and Disease. Trends Mol Med 22:458-78
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
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
Taur, Ying; Jenq, Robert R; Perales, Miguel-Angel et al. (2014) The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood 124:1174-82
Taur, Ying; Pamer, Eric G (2014) Harnessing microbiota to kill a pathogen: Fixing the microbiota to treat Clostridium difficile infections. Nat Med 20:246-7
Kinnebrew, Melissa A; Lee, Yeon Joo; Jenq, Robert R et al. (2014) Early Clostridium difficile infection during allogeneic hematopoietic stem cell transplantation. PLoS One 9:e90158
Taur, Ying; Pamer, Eric G (2013) The intestinal microbiota and susceptibility to infection in immunocompromised patients. Curr Opin Infect Dis 26:332-7
Ubeda, Carles; Bucci, Vanni; Caballero, Silvia et al. (2013) Intestinal microbiota containing Barnesiella species cures vancomycin-resistant Enterococcus faecium colonization. Infect Immun 81:965-73
Taur, Ying; Xavier, Joao B; Lipuma, Lauren et al. (2012) Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis 55:905-14
Jenq, Robert R; Ubeda, Carles; Taur, Ying et al. (2012) Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J Exp Med 209:903-11