Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Investigating the role of GATAD2 and the NuRD complex in FOXO/daf-16 regulation of stem cell fate

Award Number: R15GM150082
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2029

Group Awards By:

View Award Description

Investigating the role of GATAD2 and the NuRD complex in FOXO/daf-16 regulation of stem cell fate - In order for stem cells to replenish damaged cells and sustain normal turnover, they must retain multipotency, or the capacity to produce multiple cell types, during periods of quiescence or non - division. The FOXO family of transcription factors is critical for both s tem cell maintenance and quiescence. However, the mechanisms by which FOXO proteins impact developmental pathways to control cell fate are poorly understood and represent a major knowledge gap. The long-term goal of this lab is to elucidate the mechanisms by which developmental pathways are regulated to promote multipotency during quiescence in the tractable C. elegans model system. This powerful system allows the manipulation of genetic pathways and the characterization of stem cell models at single - cell resolution in the context of an intact organism. The single C. elegans FOXO ortholog, DAF-16, is activated during larval development in response to adverse environmental conditions to promote entry into the quiescent and stress-resistant dauer larva stage. Throughout dauer arrest, epidermal seam cells are quiescent and multipotent, serving as an effective stem cell model. During non-dauer larval stages, seam cells undergo self-renewing divisions. Upon reaching adulthood, seam cells differentiate, lose their multipotency, and express adult-specific genes which are useful markers of adult cell fate. We previously showed that FOXO/daf-16 is required to maintain developmental arrest during dauer and prevent precocious adoption of adult cell fate in seam cells. The overall goal of this proposal is to elucidate the upstream and downstream steps of a molecular pathway suggested by our preliminary data. This pathway centers on dcp-66, the ortholog of human GATAD2A and GATAD2B, which encode proteins that are part of the nucleosome remodeling and deacetylase (NuRD) complex. In Aim 1, we will use test the hypothesis that FOXO/daf-16 regulates GATAD2/dcp- 66 activity indirectly via three conserved RNA-binding proteins identified in our prior work. In Aim 2, we will determine the mechanism by which GATAD2/DCP-66 regulates adult cell fate. We will use RNAi and genetic mutants to test the requirement of other NuRD components for regulating adult cell fate during dauer. We will also use qPCR, mRNA-sequencing, and ChIP-sequencing to identify genes that are regulated by dcp-66. The proposed work is significant because it will illuminate how the regulation of developmental pathways is coordinated with the regulation of quiescence in multipotent cells. This foundational knowledge is expected to advance our understanding of the capacity of quiescent stem cells to replenish cells as needed to maintain tissues over time.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $531,680 )
2026	2026	CENTRAL MICHIGAN UNIVERSITY	119 BOVEE UNIVERSITY CTR	MOUNT PLEASANT	MI	48858	ISABELLA	USA	Biomedical Research and Research Training	000	2	5/11/2026	COMPETING CONTINUATION	$531,680
														Subtotal = $531,680

Issue Date FY: 2024 ( Subtotal = $60,571 )
2024	2024	CENTRAL MICHIGAN UNIVERSITY	119 BOVEE UNIVERSITY CTR	MOUNT PLEASANT	MI	48858	ISABELLA	USA	Biomedical Research and Research Training	000	1	5/21/2024	SUPPLEMENT FOR EXPANSION	$60,571
														Subtotal = $60,571

Issue Date FY: 2023 ( Subtotal = $434,505 )
2023	2023	CENTRAL MICHIGAN UNIVERSITY	119 BOVEE UNIVERSITY CTR	MOUNT PLEASANT	MI	48858	ISABELLA	USA	Biomedical Research and Research Training	000	1	4/5/2023	NEW	$434,505
														Subtotal = $434,505

Grand Total All Awards = $1,026,756

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigating the role of GATAD2 and the NuRD complex in FOXO/daf-16 regulation of stem cell fate

Award Number: R15GM150082

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer