Award
National Institute of Diabetes and Digestive and Kidney Diseases 5R01DK135089-03
Why do Down Syndrome patients have high risk of Hirschsprung disease?
Recipient
New York University School of Medicine
Award Amount
$845,991.00
Ceiling
$845,991.00
Awarded
July 17, 2026
Identifier
5R01DK135089-03
The award funds research to uncover genetic mechanisms linking chromosome 21 dosage in Down Syndrome to increased risk of Hirschsprung disease, using human genetics, stem cell models, and mouse models.
Description
This project investigates the genetic mechanisms by which increased chromosome 21 dosage leads to associations of specific diseases in Down Syndrome (DS), specifically Hirschsprung disease (HSCR). It focuses on how RET enhancer variants that decrease its expression are further compromised by increased dosage of chromosome 21, likely through SOD1 and other chromosome 21 genes. The research involves human genetics, functional genomics in engineered pluripotent stem cells (iPSC), and mouse models of HSA21 genes and RET to understand mechanisms leading to HSCR-associated DS.