# Regulation of Metabolic Programs for Host Tolerance to Inflammation

> **NIH NIH K08** · YALE UNIVERSITY · 2021 · $163,080

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal describes a rigorous training program leading to the career development of Dr. Andrew Wang as
an independent physician scientist.
The principal investigator is a physician scientist with a PhD in Immunobiology who recently completed clinical
fellowship training in Rheumatology. His career goal is to become an independent investigator studying tissue
tolerance to inflammation. He proposes to expand his training in inflammation biology through an intensive
training research experience under the mentorship of Dr. Ruslan Medzhitov, a pioneer and world leader with
unparalleled intellectual and technical insight into tackling the complex biology of inflammation. In addition to
intellectual grooming and hands-on training in Dr. Medzhitov's lab, a proposed rigorous series of didactic
coursework and a carefully selected advisory committee comprised of physician-scientists with a broad range
of expertise related to this project and with extensive experience in successfully fostering physician-scientist
careers will equip him with the necessary skills to become a successful independent investigator.
The research objective of this proposal is to understand how glucose metabolism regulates tissue tolerance to
different types of inflammation. Preliminary data for this proposal reveals that nutritional supplementation
enhances lethality in the Listeria model of bacterial sepsis while it protects against lethality in the flu model of
viral sepsis. The causative component of food was determined to be glucose. Lethality was independent of the
extent of systemic inflammation or pathogen burden. Findings were recapitulated in sterile models of bacterial
and viral sepsis where therapeutic blockade of glucose metabolism with 2-deoxy glucose in the
lipopolysaccharide model of bacterial sepsis lead to protection from mortality while therapeutic blockade of
glucose metabolism in a Poly I:C model of viral sepsis lead to enhanced mortality, independent of the degree
of inflammation. We hypothesized that different types of inflammation induced different metabolic states in
order to coordinate appropriate activation of cytoprotective responses necessary for tissue protection from
inflammatory damage. This proposal examines the role of ketone biology in mediating protection to bacterial
inflammation and the role of the interferon alpha-mediated glucose-dependent unfolded protein response in
viral inflammation.
This proposal serves as a training vehicle for Dr. Andrew Wang to become an expert in inflammation,
metabolic control, and tissue response to inflammation so that he can apply his expertise to the field of
rheumatic diseases.

## Key facts

- **NIH application ID:** 10077534
- **Project number:** 5K08AI128745-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Andrew Wang
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $163,080
- **Award type:** 5
- **Project period:** 2017-01-17 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077534

## Citation

> US National Institutes of Health, RePORTER application 10077534, Regulation of Metabolic Programs for Host Tolerance to Inflammation (5K08AI128745-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10077534. Licensed CC0.

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