ABSTRACT
This Mentored Career Development (K01) Award proposal will provide an outstanding educational environment,
mentoring, and training for Dr. Jillian Hurst, a pediatric infectious diseases researcher whose overarching career
goal is to integrate clinical and biological data to further our understanding of the role of the microbiome and
related host factors in modifying susceptibility to common childhood infections Dr. Hurst originally trained in
biochemistry and molecular biology and has worked in translational pediatric research for the past five years.
This career development award will allow her to receive training in omics and advanced statistical analyses using
large datasets, permitting her to lead multidisciplinary teams that use large clinical and omics datasets to
evaluate factors underlying common pediatric infections. The proposed research studies center on the role of
the upper respiratory microbiome in the development and recurrence of acute otitis media (AOM; middle ear
infection), the most common infectious disease of childhood. Dr. Hurst will test the hypothesis that early life
antibiotic exposures disrupt the development of the URT microbiome, predisposing children to AOM and other
common respiratory infections. She will use over eight years of electronic health records data, banked
longitudinal upper respiratory specimens collected from children from birth to age 2, and samples and data from
a prospective cohort of children with recurrent AOM to accomplish the following specific aims: 1) Assess the
impact of early life antibiotic exposures on recurrent AOM development.; 2) Delineate the effects of early life
antibiotic exposures on URT microbiome development; and 3) Evaluate associations between antibiotic
exposures and the URT microbiome in children with recurrent AOM. Findings from these studies will guide the
development of new strategies to prevent and treat AOM and associated infections, including guidance for
antibiotic use and identification of therapeutic targets within the URT microbiome that could be leveraged to
restore URT microbiome function and improve respiratory health among young children. Mentorship will be
provided by a group of three established investigators with complementary expertise: Dr. Christopher Woods,
an infectious diseases physician and clinical epidemiologist with expertise in the evaluation of host responses to
infectious agents; Dr. Matthew Kelly, a pediatric infectious diseases physician with expertise in the human
microbiome and clinical omics analyses; and Dr. Benjamin Goldstein, a biostatistician with expertise in the use
of electronic health records data for population health analyses. Additionally, Dr. Hurst will be advised by internal
and external advisors with expertise in antimicrobial stewardship, pediatric otolaryngology, health informatics
and omics analyses, and the treatment and pathophysiology of AOM. Completion of the proposed training and
research activities will establish Dr. Hurst as an independent investigator who will lead an NIH-funded research
program investigating host factors and exposures underlying common infections in children.