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Hematopoietic Stem Cell Dysfunction and Regeneration in Severe Infection

Award Number: R35GM131842
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2019
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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Hematopoietic Stem Cell Dysfunction and Regeneration in Severe Infection - Project Summary Survivors of severe infection often exhibit prolonged immune dysfunction, physical and cognitive decline, and significantly elevated risk of mortality. How to improve long-term outcomes of survivors of severe infection is of major clinical significance and represents an important open question. Here, we will explore the long-term impact of shock-like infection, using models of tick-born infection and sepsis, on hematopoietic stem cell (HSC) function by asking: What are the long-term impacts of severe infection on hematopoiesis and HSC function? Are HSCs primed to produce particular lineages? Can we protect HSCs in severe disease to improve outcomes in survivors? How is the bone marrow microenvironment (or niche), where HSCs reside, impacted by severe disease? Sepsis is a severe systemic infection that causes vascular dysfunction and organ failure, and represents a major cause of mortality in hospitals. Despite advances in understanding of sepsis pathophysiology, treatments are limited, and mortality remains high. At the same time, antibiotic resistance, the spread of vector born pathogens, and the lack of vaccines for emerging infections are important factors in the global increase in infectious disease burden. As serious infections continue to emerge and rates of sepsis have increased, so has the number of survivors. Here, we aim to understand the biological impact of severe, acute infection on the function of HSCs and hematopoiesis during recovery, to provide new insight into the decline in health after serious infection. Continuous and balanced blood production relies on HSCs and progenitors and is essential for life. The process of blood production generates cells of the immune system critical for host defense, as well as all blood components necessary for oxygenation (red blood cells) and vascular hemostasis (platelets). HSCs are positioned at the top of the blood system hierarchy, held in reserve, but can be activated by acute inflammation to produce immune cells. What is unknown is how acute inflammatory insults impact stem cell function in the long-term stages of recovery. In addition to immune cells, blood components (RBCs and platelets) play underappreciated roles in host defense and are important for regeneration and function of all tissue systems. Ultimately, we will test strategies to improve the number and function of stem cells in survivors of severe infectious illness.


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	2023	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE # A34	ALBANY	NY	12208	ALBANY	USA	Biomedical Research and Research Training	000	5	11/5/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $405,000 )
2023	2023	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Biomedical Research and Research Training	000	5	3/16/2023	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2022 ( Subtotal = $405,000 )
2022	2022	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Biomedical Research and Research Training	001	4	6/22/2022	NON-COMPETING CONTINUATION	$40,502
2022	2022	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Biomedical Research and Research Training	000	4	3/30/2022	NON-COMPETING CONTINUATION	$364,498
														Subtotal = $405,000

Issue Date FY: 2021 ( Subtotal = $405,000 )
2021	2021	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Biomedical Research and Research Training	000	3	3/12/2021	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2020 ( Subtotal = $405,000 )
2020	2020	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Biomedical Research and Research Training	000	2	3/5/2020	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2019 ( Subtotal = $405,000 )
2019	2019	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Biomedical Research and Research Training	000	1	3/28/2019	NEW	$405,000
														Subtotal = $405,000

Grand Total All Awards = $2,025,000

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Hematopoietic Stem Cell Dysfunction and Regeneration in Severe Infection

Award Number: R35GM131842

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2019

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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