# Forward genetic analysis of biliary system formation

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2024 · $340,032

## Abstract

PROJECT SUMMARY
Malformation of the biliary system could lead to cholestatic liver diseases, including biliary atresia, the most
common infantile liver disease. A developmental anomaly of the biliary system could lead to biliary atresia and
other cholestatic liver diseases. To understand the genetic factors that contribute to the pathogenesis of biliary
atresia, we undertook a forward genetic screen to identify previously unappreciated genes and pathways
responsible for biliary system formation in zebrafish. We have successfully established new 24 zebrafish
mutants, which specifically affect the biliary system. We will investigate the molecular mechanisms underlying
biliary system phenotypes in zebrafish by using our innovative computational algorithms to quantify subtle
differences in three-dimensional biliary branching patterns and utilize machine-learning-based algorithms to
characterize their phenotypes unbiasedly. Building on this work, we will extend our studies to human biliary
atresia and other biliary system disease patient samples to investigate the pathology. Successful execution of
this collaborative scientific endeavor promises to develop important new scientific insights into biliary system
formation. It may have profound implications for our understanding of the pathology of biliary system diseases.

## Key facts

- **NIH application ID:** 10849651
- **Project number:** 5R01DK103637-08
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Takuya Sakaguchi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $340,032
- **Award type:** 5
- **Project period:** 2015-07-25 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10849651

## Citation

> US National Institutes of Health, RePORTER application 10849651, Forward genetic analysis of biliary system formation (5R01DK103637-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10849651. Licensed CC0.

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