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Decoding innate immune signaling in normal and myelodysplastic hematopoiesis

Award Number: R35HL166430
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2029

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Decoding innate immune signaling in normal and myelodysplastic hematopoiesis - Abstract Myelodysplastic Syndromes (MDS) are heterogenous and poorly understood hematopoietic stem cell (HSC) failure syndromes common in individuals >60 years of age. With increased life expectancies, the incidence of MDS continues to rise, and will soon be the most prevalent hematologic disorder in elderly. There are no effective treatments for MDS patients, due to an insufficient understanding of the underlying pathobiology and a lack of faithful mouse models. Our research program is focused on filling these gaps, and then leveraging the resulting knowledge and tools to develop effective drug therapies. Already, we have discovered genetically-driven aberrant activation of innate immune pathways in MDS HSCs. We have also identified a critical function of innate immune pathways in normal HSCs, which has implications for chronic immune-related disorders, cardiovascular diseases, and hematopoiesis. We hypothesize that dysregulated innate immune signaling is a major contributor to the initiation and development of MDS, and is a feasible therapeutic target. Herein, we propose to test this hypothesis by carrying out the following complimentary 3-part research program: (1) Dissect the genetic and cellular underpinnings of MDS HSCs, with an emphasis on cell-intrinsic and cell-extrinsic immune-inflammatory factors. (2) Identify and characterize novel signaling pathways driving MDS phenotype in HSCs. (3) Develop novel therapeutic strategies for the treatment of MDS. The results of our research program will advance our paradigm-shifting model of the initiation, progression, and treatment of MDS.


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 = $981,728 )
2025	2025	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Blood Diseases and Resources Research	000	3	12/11/2024	NON-COMPETING CONTINUATION	$981,728
														Subtotal = $981,728

Issue Date FY: 2024 ( Subtotal = $1,080,025 )
2024	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Blood Diseases and Resources Research	001	2	6/12/2024	NON-COMPETING CONTINUATION	$88,166
2024	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Blood Diseases and Resources Research	000	2	12/20/2023	NON-COMPETING CONTINUATION	$991,859
														Subtotal = $1,080,025

Issue Date FY: 2023 ( Subtotal = $1,113,000 )
2023	2023	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Blood Diseases and Resources Research	000	1	12/26/2022	NEW	$1,113,000
														Subtotal = $1,113,000

Grand Total All Awards = $3,174,753

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Decoding innate immune signaling in normal and myelodysplastic hematopoiesis

Award Number: R35HL166430

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2029

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