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Hematopoietic Stem Cell engraftment in the injured niche

Award Number: R01HL162649
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2024

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Hematopoietic Stem Cell engraftment in the injured niche - Abstract: Hematopoietic stem cell transplantation remains the only curative treatment for many patients with hematological disease. A lack of understanding of how hematopoietic stem cells and progenitors engraft in the regenerating marrow hampers the development of new therapies to improve transplantation efficiency, especially when donor stem cells are limiting. A major limitation for progress was the lack of tools to examine differentiation in situ. We have developed methods to image and fate map virtually all steps of blood cell production in situ. The objective of this proposal is to generate an atlas of hematopoietic cell engraftment and determine how the local microenvironment promotes engraftment. We have found that different subsets of sinusoids and megakaryocytes identify physically distinct regions of high or poor donor cell engraftment. We hypothesize that regions of high donor cell engraftment represent progenitor niches that selectively promote short-term engraftment. In contrast areas of low donor cell engraftment represent stem cells niches that promote clonal stem cell renewal and long-term engraftment. We will test this hypothesis in two aims. In Aim 1 we will generate an imaging atlas of regenerative hematopoiesis and test the hypothesis that progenitors and stem cells differentially localize to different bone marrow regions. In Aim 2 we will investigate the mechanisms through which unique niches in the regenerating microenvironment support regenerative hematopoiesis.


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 = $0 )
2025	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Blood Diseases and Resources Research	001	3	4/29/2025	NON-COMPETING CONTINUATION	$0
2025	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Blood Diseases and Resources Research	000	3	12/31/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $515,739 )
2024	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Blood Diseases and Resources Research	001	3	6/21/2024	NON-COMPETING CONTINUATION	$42,100
2024	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Blood Diseases and Resources Research	000	3	2/15/2024	NON-COMPETING CONTINUATION	$473,639
														Subtotal = $515,739

Issue Date FY: 2023 ( Subtotal = $526,265 )
2023	2023	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Blood Diseases and Resources Research	000	2	2/14/2023	NON-COMPETING CONTINUATION	$526,265
														Subtotal = $526,265

Issue Date FY: 2022 ( Subtotal = $526,265 )
2022	2022	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Blood Diseases and Resources Research	000	1	3/1/2022	NEW	$526,265
														Subtotal = $526,265

Grand Total All Awards = $1,568,269

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Hematopoietic Stem Cell engraftment in the injured niche

Award Number: R01HL162649

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2024

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