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Early myeloid lineage specification mechanisms at the top of the hematopoietic hierarchy

Award Number: R56DK139218
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2025
PERIOD OF PERFORMANCE END DATE: 08/14/2026

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Early myeloid lineage specification mechanisms at the top of the hematopoietic hierarchy - Elucidating how lineage specification occurs at the top of the hematopoietic hierarchy has tremendous implications for treating impaired blood production. The critical contribution of lineage-biased multipotent progenitors (MPPs) to steady-state hematopoiesis emphasizes the importance of uncovering the mechanisms underlying lineage-biased MPP production from hematopoietic stem cells (HSCs) and the lineage specification mechanisms at the MPP population. Despite its potential clinical significance to efficiently modulate myeloid cell production, how initial myeloid lineage specification occurs at the adult HSCs and MPP populations remain poorly understood. Our recent discoveries of distinct subsets within a granulocyte/macrophage (G/M)-biased MPP, MPP3 and their differential lineage potentials indicate the bifurcation point for G/M versus erythroid lineage at the MPP3. Based on those findings, this proposal aims to establish signaling pathways that control G/M versus erythroid cell production at the HSC and MPP levels. In Aim 1, we will investigate the role of Notch2 signaling in the production of erythroid lineage cells using old mice and Notch2 gain-of-function mice. In Aim 2, we will interrogate the function of unfolded protein response (UPR) signaling in the production of myeloid cells in vivo using chemical activators and inhibitors. Collectively, these studies will verify the function of Notch2 and UPR signaling in the production of erythroid and myeloid cell production in vivo, respectively.


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: 2025 ( Subtotal = $86,856 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/11/2025	NEW	$86,856
														Subtotal = $86,856

Grand Total All Awards = $86,856

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Early myeloid lineage specification mechanisms at the top of the hematopoietic hierarchy

Award Number: R56DK139218

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/15/2025

PERIOD OF PERFORMANCE END DATE: 08/14/2026

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