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

Signaling dynamics in orchestrating stem cell functions during mammalian tissue regeneration

Award Number: R01AR083920
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2025
PERIOD OF PERFORMANCE END DATE: 04/30/2030

Group Awards By:

View Award Description

Signaling dynamics in orchestrating stem cell functions during mammalian tissue regeneration - Summary Normal tissue structure and function rely on the regenerative capacities of tissue resident stem cells. These stem cells engage in essential activities like proliferation, migration, and differentiation, which must be carefully coordinated through dynamic signaling interactions to ensure effective tissue regeneration. Disruption of this process can give rise to diseases, including cancer. Thus, comprehending how dynamic signaling activations orchestrate stem cell behaviors to regenerate tissue and sustain tissue function is of paramount importance for advancements in regenerative medicine and cancer therapy. The inability to simultaneously track the dynamic signaling changes and stem cell activities in most mammalian tissues has been limiting our knowledge of the signaling mechanism of stem cell coordination. By generating novel signal sensors and employing our intravital imaging approach on a tissue regeneration model, the hair follicle, our previous studies have overcome this challenge and enable us to interrogate the functional significance of signaling dynamics at the single-cell level in orchestrating regenerative cell behaviors. Previous studies in culture systems and simple epithelial models have discovered regulatory roles of the distinct signal dynamics for specific cell behaviors. It remains largely unclear how dynamic signaling activations orchestrate diverse behaviors during complex tissue regeneration. Here, we study this question by using mouse hair follicle regeneration as a model, which requires both epithelial and mesenchymal signals. We hypothesize that stem cell behaviors are directly coordinated by epithelial ERK signal dynamics and indirectly influenced by TGFβ-mediated mesenchymal organization. We will test this hypothesis by defining the dynamics of the epithelial ERK (Aim 1) and mesenchymal TGFβ (Aim 2) signals and assessing the functional implications of those dynamics on stem cell behaviors and functions. We will apply intravital imaging, genetic, optogenetic, and pharmacological manipulations, as well as novel molecular analyses to gain new insights into the mechanisms by which dynamic signals orchestrate different cell behaviors to support effective tissue regeneration and uphold normal tissue architecture. The outcomes of the research will significantly advance our knowledge of the signaling mechanisms that both promote and disrupt tissue regeneration, which will pave the way for the development of innovative strategies to treat various diseases in the future.


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 = $321,141 )
2026	2026	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	4/9/2026	NON-COMPETING CONTINUATION	$321,141
														Subtotal = $321,141

Issue Date FY: 2025 ( Subtotal = $355,938 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	6/25/2025	NEW	$355,938
														Subtotal = $355,938

Grand Total All Awards = $677,079

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Signaling dynamics in orchestrating stem cell functions during mammalian tissue regeneration

Award Number: R01AR083920

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2025

PERIOD OF PERFORMANCE END DATE: 04/30/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer