# Interactions of Intestinal Epithelial Cells, The Innate Immune System and Gut Microbiota During Dysbiosis

> **NIH NIH K01** · UNIVERSITY OF COLORADO DENVER · 2020 · $53,559

## Abstract

PROJECT SUMMARY/ABSTRACT
Candidate: The applicant is an instructor in the Allergy and Clinical Immunology Division at the University of
Colorado Anschutz Medical Campus. The applicant’s thesis work under the mentorship of Dr. Ramesh Akkina
at Colorado State University focused on translational research utilizing humanized mice to develop novel
therapies against HIV infection. During his Post-doctoral training, Dr. Neff developed methods to characterize
the im pact of the fecal m icrobiom e on adaptive im m une cells, found regulatory T cell inducing products in bacteria
and characterized the impact of HIV infection on immune cells in the lung.
Environment: At the University of Colorado, the applicant has a mentoring team with immunology, mucosal
immunology, inflammation and microbiome expertise in primary mentor Dr. Brent Palmer, and co-mentors Drs.
Catherine Lozupone, Sean Colgan, and Laurel Lenz. The applicant will continue close collaboration with Drs.
Nichole Reisdorph and Timothy Bushnell who will serve as technical advisors for UPLC, mass spectrometry and
CyTOF. The applicant’s training plan during the award includes bioinformatics, immunology, biostatistics,
responsible conduct of research, and programs in grant writing and career development.
Research: Chronic immune activation is a hallmark of HIV infection and recently, changes in the composition of
the enteric microbiome have been implicated as a driving factor. However, the mechanisms of host:microbiome
interactions are poorly understood. We showed that the fecal microbiome from those with HIV has inflammatory
properties not seen in taxonomically similar healthy subjects. Using this HIV-associated microbiome as a model
present a unique opportunity to identify causal bacteria and the mechanisms in which they lead to cell activation.
The applicant’s long-term goal is to develop a deeper understanding of the bacterial products that drive chronic
immune activation as a means to advance treatment strategies for inflammatory gastrointestinal diseases. This
proposal will evaluate the mechanisms of microbiota:host interactions. Based on previous findings, which
indicated peptidoglycan (PGN) and lipopollysaccharide (LPS) as drivers of infammatory responses, this proposal
will also investigate if specific variants of PGN and LPS differentally induce aberrant activation. The central
hypothesis is that specific PGN and LPS forms found with bacteria increased during HIV convey differential
inflammatory properties. The first aim will characterize the interactions of epithelial cells, subsets of innate
immune cells and the microbiome during HIV dysbiosis in order to determine rare bacteria that cause
inflammation. The second aim will focus on purifying PGN and LPS to determine if strain specific forms of these
bacterial products are responsible for inducing aberrant cell activation. The findings here could have global
implications of the treatment of chronic immune activation seen in multiple disease...

## Key facts

- **NIH application ID:** 10200990
- **Project number:** 3K01DK121864-02S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Charles Preston Neff
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $53,559
- **Award type:** 3
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200990

## Citation

> US National Institutes of Health, RePORTER application 10200990, Interactions of Intestinal Epithelial Cells, The Innate Immune System and Gut Microbiota During Dysbiosis (3K01DK121864-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10200990. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*