The Candidate, Michael E. Watson, M.D., Ph.D., is a faculty member (Assistant Professor) of the Division of Pediatric Infectious Diseases at the University of Michigan. He completed a residency in Pediatrics and fellowship in Pediatric Infectious Diseases at Washington University where he began his research on the bacterial pathogen Streptococcus pyogenes under the guidance of Michael Caparon, Ph.D., Professor of Microbiology. In July 2013 he was recruited to the University of Michigan and immediately appointed as a faculty scholar to the Child Health Research Center (CHRC) K12 Career Development Award which funded Dr. Watson for 3 years. The Immediate Goal of this K08 Award is to provide an additional 3 years of research experience protected from clinical and administrative duties (?75% research effort) in order to acquire further training in the investigation of bacterial pathogenesis related to colonization and infection at mucosal sites and the use of advanced genomic analysis methodology. The Long-Term Goal is to become an independent, extramurally-funded, pediatric physician-scientist. The Research Environment at the University of Michigan is exceptional and currently ranks 9th among all research-oriented medical schools according to the 2017 US News and World Report. The Candidate has developed a comprehensive Career Development Plan. Dr. Watson has recruited co-mentors including Harry L.T. Mobley, Ph.D., Professor of Microbiology, and Suzanne R. Dawid, M.D., Ph.D., Associate Professor of Pediatric Infectious Diseases and Microbiology. Dr. Mobley has a distinguished career of >30 years in microbial pathogenesis research and has previously mentored >33 fellows and junior faculty members. Dr. Dawid provides expertise in streptococcal bacterial pathogenesis and mucosal colonization. Dr. Watson has established a Scientific Advisory Subcommittee for technical expertise and a Career Advisory Subcommittee composed of senior clinician-scientists from Pediatrics who will help him navigate an academic medicine career. In addition, Dr. Caparon at Washington University will continue serving as an external advisor. Research Strategy: The Central Hypothesis is that S. pyogenes persister strains successfully evade host mucosal immunity by negatively regulating the expression of virulence factors or antigens necessary for the activation of cytokine IL-17A-mediated leukocyte recruitment.
The Specific Aims are: 1) Identify and characterize host leukocyte populations necessary to promote streptococcal mucosal clearance; and 2) Characterize streptococcal persister strains in mucosal epithelial tissues. The proposed work is innovative, capitalizing on the use of a long-term, mucosal carriage murine model for S. pyogenes developed by the Candidate, combined with transcriptomic and metabolomic profiling to characterize streptococcal persister strains in vivo. The Rationale is that through this proposed work it may be possible to develop novel strategies to stimulate mucosal immunity, or specifically target the metabolic activities of long- term persister strains, to promote streptococcal eradication from the mucosal epithelial environment.

Public Health Relevance

This K08 Career Development Award will provide the PI with a research training period in order to provide the necessary research experience and expertise to successfully transition from a mentored junior investigator status to an independent clinician-scientist capable of acquiring significant external funding. The Award will provide sufficient protected time from clinical service obligations to permit the PI to conduct the scientific research and gain the necessary skills to establish independence. The PI will utilize this research experience to gain additional training and knowledge in the investigation of the basic science and bacterial pathogenesis of Streptococcus pyogenes and mechanisms of chronic persistence in mucosal epithelial tissues.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08AI130362-01A1
Application #
9526764
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
GU, Xin-Xing
Project Start
2018-02-05
Project End
2021-01-31
Budget Start
2018-02-05
Budget End
2019-01-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pediatrics
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109