# The role of HMGB1 in gut antimicrobial defense and the pathophysiology of inflammatory bowel disease

> **NIH NIH K08** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $166,212

## Abstract

PROJECT SUMMARY/ABSTRACT
 This is a K08 Mentored Clinical Scientist Research Career Development Award application for Dr.
Jeannette S. Messer, a Pathway to Independence Instructor in The University of Chicago Department of
Medicine. Her long-term goal is to become an internationally recognized expert and researcher in the field of
host-microbe interactions in human inflammatory diseases. In order to achieve this goal, she will require
training to address four defined gaps in her knowledge: translational research [Gap #1], gnotobiotic mouse
models [Gap #2], microbiology [Gap #3], and bioinformatic techniques to study microbial populations [Gap #4].
Dr. Messer has assembled a multidisciplinary team of expert mentors and scientists with significant experience
in human inflammatory bowel disease, gnotobiotic mouse utilization and management, microbiology, and
bioinformatic approaches to analysis of microbial populations of the gut to close these gaps in knowledge and
remove the identified barriers to her transition to independence and achievement of her long term goal.
 Inflammatory bowel diseases (IBD) are diseases of chronic diarrhea and abdominal pain that affect an
estimated 1.6 million Americans. Bacteria are thought to play an important role in IBD pathophysiology
through activation of mucosal immune responses. However, the mechanisms through which bacteria trigger or
perpetuate mucosal immune responses are still poorly understood. Therefore, there is an urgent unmet need
to determine how bacteria contribute to immune activation and mucosal damage during IBD in order to develop
effective therapies that take the microbial component of the disease into account.
 High mobility group box 1 (HMGB1) is produced in intestinal epithelial cells (IEC) in response microbes.
HMGB1 is decreased in IEC from active IBD lesions and conditional deletion of HMGB1 from IEC exacerbates
colitis in murine models. The colitis seen in mice lacking IEC HMGB1 is characterized by increased IEC death
and in vitro studies have shown that IEC lacking HMGB1 are more susceptible to apoptosis when challenged
with the bacterial cell wall component muramyl dipeptide. HMGB1 is also found in stool and concentrations of
this protein in the stool are increased during active IBD. Dr. Messer has now found that mice conditionally
deficient in IEC HMGB1 also have evidence of dysbiosis and the intestinal barrier between bacteria and host
tissues is compromised. These factors suggest that HMGB1 may have a role in antimicrobial defense in the
intestine. Therefore, experiments in this study will test the hypothesis that HMGB1 plays an essential role in
maintaining gut microbial commensalism and loss of HMGB1-mediated gut antimicrobial defense, in conditions
such as IBD, leads to microbe-induced inflammation and mucosal damage.
 In Aim 1 Dr. Messer will determine mechanisms of HMGB1-mediated gut antimicrobial defense with the
goal of understanding how HMGB1 regulates bacterial colonization a...

## Key facts

- **NIH application ID:** 9957057
- **Project number:** 5K08DK114713-05
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Jeannette Sophia Messer
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $166,212
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957057

## Citation

> US National Institutes of Health, RePORTER application 9957057, The role of HMGB1 in gut antimicrobial defense and the pathophysiology of inflammatory bowel disease (5K08DK114713-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9957057. Licensed CC0.

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