Epigenetic control of cardiac lineage commitment by QSER1 and TET1

Active Project Grant Awarded Last action

Award ID
F31HL186590
Recipient
Awarding agency
Obligated
$50,114

Award facts

Assistance listing
93.837 Cardiovascular Diseases Research
Completion date 0% complete
Place of performance
New York, NY 10065, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
The precise regulation of gene expression during early development is governed by dynamic epigenetic mechanisms, including DNA methylation and chromatin accessibility. Disruption of these processes can lead to developmental disorders, such as congenital heart disease (CHD), which affects nearly 1% of live births. Recent studies identified QSER1 as a novel methylation regulator that protects developmental genes from hypermethylation in coordination with the 5-methylcytosine dioxygenase TET1. While TET1 is known to play essential roles in cardiac development, the contribution of QSER1 to cardiac lineage commitment remains unknown. This project seeks to understand how QSER1 and TET1 regulate epigenomic remodeling during cardiac lineage specification from human pluripotent stem cells, with the overarching goal of identifying fundamental epigenetic mechanisms underlying heart development. Aim 1 will define the requirement of QSER1 and TET1 for maintaining cardiac epigenome integrity. Genome-wide bisulfite sequencing, atac-SEQ, chip-SEQ, and HI-C will be performed in WT, QSER1 knockout (KO), TET1 KO, and double KO (DKO) hescs during cardiac differentiation to assess how these regulators shape DNA methylation, chromatin accessibility, transcription factor occupancy, and 3D genome architecture. Aim 2 will determine the stage-specific requirement and timing of QSER1-TET1 function during differentiation. Using inducible shrna knockdown of QSER1 and temporal CO-immunoprecipitation, this aim will pinpoint when QSER1 and TET1 function is most critical and whether their interaction is stable or dynamic during the transition from pluripotency to cardiac commitment. Aim 3 will identify QSER1-interacting proteins during cardiac differentiation using rime and IP-MS, followed by targeted validation of interactors involved in chromatin remodeling and enhancer regulation. By uncovering how QSER1 and TET1 coordinate the cardiac epigenomic landscape, this research will advance understanding of lineage specification and molecular mechanisms that can contribute to CHD. Ultimately, we hope these findings may lay the groundwork for innovative strategies in regenerative medicine and epigenetic therapy.

Quick answers

Who received award F31HL186590?

F31HL186590 was awarded to Weill Medical College Of Cornell University by National Heart Lung and Blood Institute (National Institutes of Health) on December 15, 2026.

How much is award F31HL186590 worth?

$50,114 has been obligated on F31HL186590.

On GovTribe

See this award's full record

  • Every transaction and subaward
  • The recipient's other awards and teaming partners
  • Similar grant awards
  • Ask GovTribe AI about this award
Try for free Login