Monday, June 30, 2025 6/30/2025

Protein Glycosylation in the Coagulopathy and Inflammation of Sepsis

Award Number: P01HL131474
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2016
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Protein Glycosylation in the Coagulopathy and Inflammation of Sepsis - SUMMARY Sepsis is life-threatening syndrome caused by the presence of harmful microorganisms in the blood and tissues and resulting in host inflammation, coagulopathy and organ dysfunction. As the leading cause of death in non-cardiac intensive care units, the incidence of sepsis continues to increase while no new effective therapies have been developed in decades. Among patients, mortality averages 25%, while many survivors experience long-term disabilities caused by thrombosis, hypoperfusion, and hyperinﬂammation. Globally, sepsis is more prevalent than cancer with millions of patients and billions of dollars of health care costs annually. Lack of molecular information of the pathophysiology of sepsis has primarily contributed to the paucity of new and more effective treatments. This program project renewal proposal continues to address this problem with novel approaches to advance the knowledge of sepsis from a descriptive to a more molecular basis. The program retains the expertise of scientists and clinicians whom together are making transformative discoveries of disease mechanisms and protective strategies targeted by the pathogen and the host in the onset and progression of sepsis. The proposed program renewal leverages comparative models of experimental sepsis applied to the discovery of disease mechanisms that rapidly remodel and regulate host blood and vascular components. Remodeling includes glycosidic and proteolytic processes that cause profound changes to the half-lives, localization, abundance, and functions of circulating and cell surface glycoproteins and platelets, linked to the coagulopathy, inflammation, and lethality of sepsis. The program is integrated by the overall hypothesis that Protein glycosylation and glycoprotein remodeling alter the coagulopathy and inflammation of sepsis. The three projects and four core facilities proposed will address this hypothesis with synergistic, interdisciplinary, and state-of-the-art approaches. Aims of the projects and cores encompass comparative molecular investigations of coagulation factors, tissue thrombosis, inflammation, serology, and pathogen burden and virulence among blood, urine, and tissue proteomes. Findings thus far have identified mechanisms that differentially identify and alter sepsis in the context of discrete pathogens including changes in pathogen virulence, supporting the emerging view that sepsis does not arise from a singular disease mechanism and may be stratified to achieve diagnostic and therapeutic benefits. Comparative analyses of experimental and human sepsis will continue as findings thus far have indicated conserved markers of disease mechanisms linked to stratification by pathogen and patient prognosis. The rationale for the aims of this program are derived from extensive supporting data and recent peer-reviewed publications. Additional discoveries that this program is poised to make will enable further advances in the mechanistic understanding of the life-threatening changes to host blood and vascular systems during sepsis and generate significant insights needed to develop more effective diagnostics and therapeutics.


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 = $2,674,150 )
2025	2025	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Blood Diseases and Resources Research	000	10	6/6/2025	NON-COMPETING CONTINUATION	$2,674,150
														Subtotal = $2,674,150

Issue Date FY: 2024 ( Subtotal = $2,622,490 )
2024	2024	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Blood Diseases and Resources Research	000	9	6/7/2024	NON-COMPETING CONTINUATION	$2,622,490
														Subtotal = $2,622,490

Issue Date FY: 2023 ( Subtotal = $2,676,393 )
2023	2023	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Blood Diseases and Resources Research	000	8	5/26/2023	NON-COMPETING CONTINUATION	$2,676,393
														Subtotal = $2,676,393

Issue Date FY: 2022 ( Subtotal = $2,677,013 )
2022	2022	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Blood Diseases and Resources Research	002	7	6/9/2022	NON-COMPETING CONTINUATION	$2,677,013
2022	2021	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Blood Diseases and Resources Research	001	6	4/5/2022	COMPETING CONTINUATION	$184,957
2022	2020	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Blood Diseases and Resources Research	000	5	4/5/2022	NON-COMPETING CONTINUATION	-$184,957
														Subtotal = $2,677,013

Issue Date FY: 2021 ( Subtotal = $2,749,234 )
2021	2021	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Blood Diseases and Resources Research	001	6	8/26/2021	COMPETING CONTINUATION	$2,749,234
2021	2020	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Blood Diseases and Resources Research	000	5	8/20/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,749,234

Issue Date FY: 2020 ( Subtotal = $2,543,485 )
2020	2020	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Blood Diseases and Resources Research	000	5	5/8/2020	NON-COMPETING CONTINUATION	$2,543,485
														Subtotal = $2,543,485

Issue Date FY: 2019 ( Subtotal = $2,543,485 )
2019	2019	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Blood Diseases and Resources Research	000	4	4/16/2019	NON-COMPETING CONTINUATION	$2,543,485
														Subtotal = $2,543,485

Issue Date FY: 2018 ( Subtotal = $2,543,485 )
2018	2018	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Blood Diseases and Resources Research	000	3	4/12/2018	NON-COMPETING CONTINUATION	$2,543,485
														Subtotal = $2,543,485

Issue Date FY: 2017 ( Subtotal = $2,543,894 )
2017	2017	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Blood Diseases and Resources Research	000	2	4/28/2017	NON-COMPETING CONTINUATION	$2,543,894
														Subtotal = $2,543,894

Issue Date FY: 2016 ( Subtotal = $2,622,437 )
2016	2016	SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE	10901 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cardiovascular Diseases Research	000	1	7/13/2016	NEW	$2,622,437
														Subtotal = $2,622,437

Grand Total All Awards = $26,196,066

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Protein Glycosylation in the Coagulopathy and Inflammation of Sepsis

Award Number: P01HL131474

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/15/2016

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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