# The Role of Macrophages in Hepatobiliary Development

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $587,584

## Abstract

Project Summary - The role of macrophages in hepatobiliary development
The liver is a vital metabolic organ, involved in nutrient metabolism and detoxification of
endogenous and exogenous products. To manage exposure to antigens and microbes, the liver
harbors ~80% of the body’s residential macrophages. The role of macrophages in liver
development is completely unknown. In our preliminary work we demonstrate that genetic or
induced loss of macrophages severely affects hepatobiliary development, reducing biliary tree
branching and affecting hepatocyte polarization. The objective in our proposed work is to employ
macrophage-deficient zebrafish and transgenic reporter strains combined with high-resolution
confocal imaging and novel image analysis methods to determine the importance of macrophages
for liver development. Our central hypothesis is that macrophages are attracted to the developing
liver bud by a temporal and location-specific expression of TNFα, and that macrophages mediate
their effect on hepatobiliary development through modulation of TGFβ signaling. Two Specific
Aims are proposed to define the role of macrophages for normal hepatobiliary development
development. In Specific Aim 1 we will identify the exact periods during development when
macrophages interact with the liver, and how their loss affects normal development and function.
Specific Aim2 will define the molecular signals by which macrophages are attracted to the
developing liver, and how macrophage-derived TGFβ signaling affects liver development. Our
proposed work will provide critical new mechanistic insight into the contribution of macrophages
to normal hepatobiliary development, and further elucidate the pathogenesis of developmental
biliary defects in childhood.

## Key facts

- **NIH application ID:** 10829466
- **Project number:** 5R01DK135270-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Wolfram Goessling
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $587,584
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829466

## Citation

> US National Institutes of Health, RePORTER application 10829466, The Role of Macrophages in Hepatobiliary Development (5R01DK135270-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10829466. Licensed CC0.

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