# Genetic Analysis of Hirschsprung Disease - Renewal

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $633,354

## Abstract

ABSTRACT:
Hirschsprung disease (HSCR), or congenital aganglionosis, results from defects in enteric neural crest cell
precursor (ENCC) development in a sex-biased manner. Through human genetic studies we have identified
and/or analyzed 35 genes and loci with multiple pathogenic alleles that explain ~62% of the population
attributable risk, with the greatest effects from mutations within the RET-EDNRB gene regulatory network
(GRN). In this proposal, we use our gene discoveries to conduct genomic, cellular and developmental analyses
in patients and mouse models, and investigate how genetic defects in RET and EDNRB signaling, and other
genetic defects, produce the cellular changes across development that can lead to aganglionosis. We propose
studies to improve HSCR risk prediction from patient genome sequence, advance the mechanistic
understanding of HSCR at the genetic and cellular levels, and identify the rate-limiting genetic steps suitable
for therapeutics. Our goals are to provide a genetic paradigm for uncovering the pathophysiology of a sex-
biased complex multifactorial disorder.

## Key facts

- **NIH application ID:** 10902082
- **Project number:** 5R01HD028088-31
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** ARAVINDA CHAKRAVARTI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $633,354
- **Award type:** 5
- **Project period:** 1991-04-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10902082

## Citation

> US National Institutes of Health, RePORTER application 10902082, Genetic Analysis of Hirschsprung Disease - Renewal (5R01HD028088-31). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10902082. Licensed CC0.

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