# The Role of Kidney FGF21 in Surviving Sepsis

> **NIH NIH K08** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $169,560

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal describes a rigorous training program leading to the career development of Dr. Sarah Huen as
an independent physician-scientist. The principal investigator is a board-certified nephrologist who recently
completed a Ph.D. program in Investigative Medicine at Yale University studying mechanisms of repair and
fibrosis in ischemic kidney injury. Her career goal is to become an independent investigator studying sepsis-
related acute kidney injury. She proposes to expand her training in immunobiology through an intensive
training research experience under the mentorship of Dr. Ruslan Medzhitov, a pioneer in innate immunity and
inflammation. In addition to didactic coursework and development of technical research skills in immunobiology
and sepsis, an advisory committee comprised of scientists and physician-scientists with a broad range of
expertise related to the project will provide both scientific and career development guidance. The research
objective of this proposal is to determine the role of the expression of Fibroblast growth factor-21 (FGF21) by
the kidney in the setting of sepsis. Preliminary data for this proposal reveal that in the mouse model of
lipopolysaccharide (LPS) sepsis there is robust induction of FGF21 expression in the renal tubular epithelium.
Mice deficient of FGF21 have more kidney dysfunction and are more susceptible to mortality in LPS sepsis.
The induction of Fgf21 in the kidney is unique to sepsis as its expression is not induced in sterile hemodynamic
injuries. The expression of renal Fgf21 in LPS sepsis can be inhibited by the reactive oxygen species (ROS)
scavenger n-acetylcysteine. Our hypothesis is that FGF21 is a ROS-inducible kidney tissue protective pathway
that is activated in response to sepsis. This hypothesis will be tested by pursuing these aims: 1) Determine the
role of renal FGF21 in promoting survival in sepsis, and 2) Identify the stress response pathway and the source
of ROS that regulate Fgf21 gene expression. The Yale University Departments of Nephrology and
Immunobiology together have extensive scientific resources that will enable the successful achievement of
these proposed aims. This proposal will define a novel renal defense mechanism activated in response to
systemic infection while preparing the applicant to develop a successful independent research career as a
physician-scientist.

## Key facts

- **NIH application ID:** 9933905
- **Project number:** 5K08DK110424-06
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** sarah huen
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $169,560
- **Award type:** 5
- **Project period:** 2016-08-29 → 2020-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933905

## Citation

> US National Institutes of Health, RePORTER application 9933905, The Role of Kidney FGF21 in Surviving Sepsis (5K08DK110424-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9933905. Licensed CC0.

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