# INTESTINAL MICROBIAL REGULATION OF ANTIVIRAL IMMUNITY

> **NIH NIH K08** · WASHINGTON UNIVERSITY · 2020 · $175,606

## Abstract

PROJECT SUMMARY
The goal of this proposal is to describe a 5-year plan to prepare Ashley Steed, MD, PhD, for independence as
a physician-scientist studying the role of the microbiome in antiviral immunity. She graduated with distinction
from Duke University with a degree in Biology and obtained her medical and research graduate degree from
Washington University School of Medicine's Medical Scientist Training Program. After completing her
residency and during her pediatric critical care fellowship, she joined Dr. Thaddeus Stappenbeck's laboratory,
where she has demonstrated that elevated basal interferon type I signaling is protective to the host during
influenza infection. This finding resolves a controversy in the influenza field. She has extended these studies
to investigate the role of the enteric microbiome in driving systemic interferon levels and the consequences for
viral infection. These findings serve as the basis for the aims in this proposal.
Washington University School of Medicine is an exemplary location for Dr. Steed to develop her research
platform with its longstanding history of NIH funded research and breadth and depth of resources. There is
frequent crosstalk among departments, as Dr. Steed's mentoring committee and collaborators demonstrate,
combining the expertise from the departments of Microbiology, Immunology, Pediatrics, and Medicine. Dr.
Stappenbeck is a leader in the field of host-microbial interactions at mucosal surfaces; thus he is an ideal
mentor for Dr. Steed because of his ability to decipher mechanisms of pathogenesis and his strong track
record in training young scientists. His laboratory is a training hub of intellectual energy with a diverse group
working on broad and creative projects. Dr. Steed will have multiple opportunities to present her work locally
and in the larger scientific community. She will take graduate level classes to enhance her knowledge in
microbiology and genomics and develop key technical skills with her collaborators.
Dr. Steed's immediate goal is to fulfill the aims outlined in this proposal. While it is clear that the enteric
microbiome is important for resistance to influenza pathogenesis, molecular understanding of this interaction
remains obscure. She recently discovered a microbially-associated metabolite, desaminotyrosine, that
enhances type I interferon signaling. This finding suggests that a specific microbial metabolite may mediate the
protective effect of the microbiome. By completing the proposed aims, Dr. Steed will 1) test the hypothesis that
desaminotyrosine protects from influenza pathogenesis by enhancing systemic interferon signaling, 2) define
the mechanism by which desaminotyrosine augments interferon signaling, and 3) identify components of the
microbiome that produce desaminotyrosine. Her laboratory's initial focus will be to further delineate these
mechanisms such that insight from her research will translate to strategies aimed at improving resistance to
viral pa...

## Key facts

- **NIH application ID:** 9823836
- **Project number:** 5K08AI135097-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Ashley Steed
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $175,606
- **Award type:** 5
- **Project period:** 2017-12-07 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9823836

## Citation

> US National Institutes of Health, RePORTER application 9823836, INTESTINAL MICROBIAL REGULATION OF ANTIVIRAL IMMUNITY (5K08AI135097-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9823836. Licensed CC0.

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