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

The role of Gasdermin D in the bone marrow microenvironment during clonal hematopoiesis progression

Award Number: R00CA289959
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2025
PERIOD OF PERFORMANCE END DATE: 01/31/2029

Group Awards By:

View Award Description

The role of Gasdermin D in the bone marrow microenvironment during clonal hematopoiesis progression - PROJECT SUMMARY Clonal hematopoiesis (CH) is a pre-malignant condition characterized by the clonal expansion of the mutated hematopoietic stem and progenitor cells (HSPCs). CH represents a significant public health concern, over 10% of individuals aged 70 and above carry CH mutations. This blood disorder predominantly affects older adults and elevates the risk of hematologic malignancies nearly 13 folds. As the US population projected to be markedly aged in the next three decades, the implications of CH will become increasingly significant. First being recognized as a distinct category of precursor myeloid disease state by WHO in 2022, there is not yet any FDA approved treatment toward CH, highlighting an urgent medical need. This project aims to investigate how inflammation, especially that originating form the non-hematopoietic cells within the bone marrow microenvironment, contributes to the CH progression. We have found Gasdermin D (GSDMD) loss-of-function in the non-hematopoietic stromal cells significantly mitigated the CH progression in mice. To further translate our findings from mice to humans, we have developed a novel human bone marrow organoid model. This model autonomously generates multi-lineage hematopoietic cells and non-hematopoietic stromal cells within a 3D vascular network, closely resembling the human bone marrow microenvironment. Notably, we generated GSDMD-/- organoids and engrafted them with patient-derived HSPCs carrying TET2 mutations, we observed a significant reduction in myeloid-biased hematopoiesis of the engrafted HSPCs with in GSDMD-/- organoids compared to WT organoids. Moving forward, we will employ spatial transcriptomic analysis coupled with single-cell RNA sequencing to uncover the mechanisms by which GSDMD influences cell-cell interactions in both mouse models and human organoid models. Ultimately, we plan to create a novel patient-derived xenograft mouse model by implanting the organoid into NSG immunodeficient mice, further advancing our ability to model human CH in vivo. The successful completion of this project will provide critical insights into the cellular and molecular mechanisms of the protective effect of GSDMD deficiency in the bone marrow microenvironment. It will lay the groundwork for potential therapeutic strategies targeting dysregulated inflammation in non- hematopoietic cells, serving as a stepping stone for my transition to independent investigations as a PI.


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 = $249,000 )
2026	2026	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	000	2	4/1/2026	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $249,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The role of Gasdermin D in the bone marrow microenvironment during clonal hematopoiesis progression

Award Number: R00CA289959

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2025

PERIOD OF PERFORMANCE END DATE: 01/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer