# Inside-out construction of the biliary system

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $368,422

## Abstract

Project Summary
The intrahepatic biliary tree functions to drain bile from hepatocytic canaliculi away from the liver. Congenital or
acquired abnormalities in the formation and patency of intrahepatic bile ducts have severe, often fatal
consequences. In the developing liver, biliary morphogenesis is a self-organizing process whereby bipotential
hepatoblasts simultaneously adopt a biliary fate and organize into a continuous tubular network without cell
division. Mounting evidence suggests that transdifferentiation of mature hepatocytes can also yield both normal
regenerative biliary morphogenesis and abnormal disease-associated biliary `ductal reactions' in the adult liver.
The mechanisms by which biliary architecture and fate are coordinated to enact this dramatic morphogenetic
program and build a functional biliary tree are largely unknown. Understanding the mechanistic basis of biliary
morphogenesis is necessary to harness the regenerative potential of the liver while avoiding the lethal
consequences of chronic and malignant liver disease. We recently discovered that de novo lumen formation
and expansion initiates biliary morphogenesis and is central to the coordination of biliary architecture and fate.
Our published and preliminary studies suggest a model wherein lumen formation creates a physical signaling
niche that feeds back to reinforce both biliary architecture and fate, thereby creating the biliary system from the
inside out. The long-term goal of this project is to understand how lumen formation and extension guides the
formation of the biliary tubular network. The successful completion of this work will address a key gap in our
understanding of how to safely build this critical organ, and limit or repair it in disease.

## Key facts

- **NIH application ID:** 10319945
- **Project number:** 5R01DK127177-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** ANDREA I MCCLATCHEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $368,422
- **Award type:** 5
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10319945

## Citation

> US National Institutes of Health, RePORTER application 10319945, Inside-out construction of the biliary system (5R01DK127177-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10319945. Licensed CC0.

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