# Dissecting microbiota-driven lymphangiogenesis in immune health and disease

> **NIH NIH DP2** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $467,159

## Abstract

Project Summary
The goal of this proposal is to investigate the role of the gut microbiota and microbiota-specific
immune responses in health and disease. The gut microbiota has been associated with a
number of immune-based diseases, including cancer, autoimmunity, IBD and infections;
however, specific mechanisms remain unclear.
Our recent findings have shown that select members of the gut microbiota drive lymphatic
development and formation of tertiary lymphoid structures. Specifically, addition of an adherent
colonic-residing bacteria, Helicobacter hepaticus, supports lymphangiogenesis and tertiary
lymphoid structure formation within the colon of colorectal tumor-bearing mice. Ultimately, this
led to an increase in immune infiltration by T cells into the tumor core.
However, how select colonic bacteria drive lymphangiogenesis and support tertiary lymphoid
structure formation and maturation remains unknown. Project 1 of this proposal will identify the
key signals responsible for bacteria-drive lymphangiogenesis using spatio-temporal analysis.
Part 2 will investigate the cell subsets responsible for tertiary lymphoid structure formation due
to lymphangiogenesis and Part 3 will assess the direct and indirect roles of gut microbes in
lymphangiogenesis in health and disease. Our overall hypothesis is that colonization with
Helicobacter hepaticus drives lymphangiogenesis and tertiary lymphoid structure maturation
through upregulation of VEGF-driven reprogrammed Lyve1+ macrophages. Completion of these
aims will lead to a completely new field of study and understanding of lymphangiogenesis in the
adult host and will also establish the necessary foundation for my career as an independent
investigator.

## Key facts

- **NIH application ID:** 10907807
- **Project number:** 5DP2AI177967-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Abigail E Overacre-Delgoffe
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $467,159
- **Award type:** 5
- **Project period:** 2023-08-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907807

## Citation

> US National Institutes of Health, RePORTER application 10907807, Dissecting microbiota-driven lymphangiogenesis in immune health and disease (5DP2AI177967-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10907807. Licensed CC0.

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