# Patient-oriented microbiome and advanced culture approaches to identifying the microbial determinants of chronic pediatric disease

> **NIH NIH K24** · UNIVERSITY OF WASHINGTON · 2024 · $125,068

## Abstract

PROJECT SUMMARY/ABSTRACT
This K24 renewal proposes salary and research support for Lucas Hoffman, MD, PhD to continue to spend at
least 25% of his time mentoring students, fellows, and junior faculty in patient-oriented research (POR) on the
microbial determinants of chronic, pediatric diseases. This proposal will enable Dr. Hoffman to continue his
productive translational research program that has already provided a successful training framework for MD
and PhD trainees in the principles and conduct of POR. This proposal describes existing translational research
projects in the Hoffman laboratory that will provide training opportunities to current and future mentees, as well
as new projects likely to emerge from this ongoing work. The proposal also provides time and infrastructure
support to help Dr. Hoffman enhance his mentoring skills, including classwork and new opportunities to interact
with trainees, and an advisory committee of experienced, senior national experts in POR. Both of the featured,
ongoing research projects provide opportunities for face-to-face interactions and leverage existing resources to
investigate novel questions and yield new resources, providing optimal opportunities for trainees:
Project 1 investigates the effects of a powerful new treatment on the gastrointestinal (GI) microbiomes and
metabolomes of people with the genetic disease cystic fibrosis (CF). This project leverages the samples and
linked biomarker and clinical data from two parallel, ongoing national observational studies of subjects with CF
before and after initiating treatment with highly-effective CFTR modulator therapy, which restores the activity of
the protein that is defective in people with CF, the cystic fibrosis transmembrane conductance regulator
(CFTR). The analysis we are performing builds on the results of a study described in my first K24 proposal that
ultimately identified a significant fecal dysbiosis in people with CF that correlated with impaired nutrition and
with abnormal fecal metabolite content, including that of bile acids. For this study, the Hoffman laboratory is
analyzing the fecal samples of enrolled subjects to test the hypothesis that CFTR modulator therapy will
change the fecal microbiomes and metabolomes of PwCF in parallel with clinical improvement.
Project 2 similarly builds on a project described in my first K24 proposal focused on the respiratory
microbiomes of people with CF that defined the respiratory tract microbiomes of people with CF during inhaled
antibiotic therapy. Using the respiratory samples and data being collected by the studies described in Project 1,
this study will test the hypothesis that CFTR modulator therapy will change both upper and lower respiratory
tract microbiomes of people with CF in parallel with each other and with clinical improvement.
Both projects provide opportunities to interact with study subjects and to develop laboratory, computational,
and analytical skills for current and future earl...

## Key facts

- **NIH application ID:** 10806591
- **Project number:** 2K24HL141669-06
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Lucas R Hoffman
- **Activity code:** K24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $125,068
- **Award type:** 2
- **Project period:** 2018-04-22 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10806591

## Citation

> US National Institutes of Health, RePORTER application 10806591, Patient-oriented microbiome and advanced culture approaches to identifying the microbial determinants of chronic pediatric disease (2K24HL141669-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10806591. Licensed CC0.

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