Sunday, August 31, 2025 8/31/2025

Inflammation Phenotypes in Pediatric Sepsis Induced Multiple Organ Failure Renewal

Award Number: R01GM108618
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: 03/01/2014
PERIOD OF PERFORMANCE END DATE: 06/30/2028

Group Awards By:

View Award Description

Inflammation Phenotypes in Pediatric Sepsis Induced Multiple Organ Failure Renewal - Project Abstract Every year over 1 million American adults and children develop overwhelming infection leading to a rotting of their body we call ‘sepsis’, and death in up to 1 of 4 afflicted. We and others have asked the question “why do patients continue to die of organ shutdown?” In the previous funding period we used clinical information and samples already obtained in our R01 funded audit of 401 children with sepsis and took advantage of the wonderful advances made this millenia in computer technology, big data, bioinformatics, and the study of human and virus genetics to understand how too much inflammation and too little immune response lead to organ shutdown. First, we used ‘Watson’ like machine learning at 24 hours to identify a sub-group of children we named PedSep-D who subsequently go on to death with organ shutdown caused by too much inflammation and clotting that we can now reverse with anti-inflammatory and anti-thrombotic therapies. Second, we used an ‘Ancestry.com’-like or ‘23 and me’-like next generation sequencing approach to identify genes in individual children that were related to too much inflammation and too little ability to kill infection which we can now treat on an individual basis using ‘precision medicine’ therapies. Third, we used molecular biology testing approaches to identify Latent Epstein Barr Virus infection as an asymptomatic preexisting high- risk condition that is associated with death when children develop sepsis. Disordered inflammation and immunity are closely related to altered metabolism. We previously linked all three to organ shutdown and death in pediatric sepsis. In the next funding period we will investigate toxic ‘metabolism’ as a cause of organ shutdown by measuring plasma metabolomics in these same 401 child samples. In Specific Aim 1 we test the hypothesis that PedSep D patients have a shift to aerobic glycolysis that drives toxic macrophage activation that can potentially be reversed with glucose restriction and / or Metformin treatment. In Specific Aim 2 we test the hypothesis that gene variants related to Inborn Errors of Metabolism contribute to organ shutdown that can be reversed using established Precision Medicine metabolic therapies. In Specific Aim 3 we test the hypothesis that Epstein Barr Virus latent infection is causally associated with organ shutdown because it induces Immuno-Metabolic reprogramming of the host response in sepsis towards aerobic glycolysis that is potentially reversed with repurposed drugs such as Metformin. We also examine methylation epigenetics in these children to begin to understand the molecular basis for this host pathogen response. Our long-term objective is to plan ‘precision’ medicine and ‘individualized’ medicine clinical trials testing therapies that address Inflammation-Immune-Metabolism dysregulation on an individual patient basis in order to further reduce death from sepsis induced organ shutdown in children.


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 = $970,912 )
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Biomedical Research and Research Training	002	10	7/23/2025	NON-COMPETING CONTINUATION	$485,456
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Biomedical Research and Research Training	001	9	3/20/2025	COMPETING CONTINUATION	$485,456
2025	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Biomedical Research and Research Training	001	9	3/20/2025	COMPETING CONTINUATION	$350
2025	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Biomedical Research and Research Training	000	8	3/20/2025	NON-COMPETING CONTINUATION	-$350
														Subtotal = $970,912

Issue Date FY: 2024 ( Subtotal = $524,648 )
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Biomedical Research and Research Training	000	9	9/4/2024	COMPETING CONTINUATION	$524,648
														Subtotal = $524,648

Issue Date FY: 2022 ( Subtotal = $416,211 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Biomedical Research and Research Training	001	8	6/22/2022	NON-COMPETING CONTINUATION	$416,211
2022	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Biomedical Research and Research Training	000	7	10/27/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $416,211

Issue Date FY: 2021 ( Subtotal = $416,211 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Biomedical Research and Research Training	000	7	7/29/2021	NON-COMPETING CONTINUATION	$416,211
														Subtotal = $416,211

Issue Date FY: 2020 ( Subtotal = $500,320 )
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	6	7/1/2020	NON-COMPETING CONTINUATION	$500,320
														Subtotal = $500,320

Issue Date FY: 2019 ( Subtotal = $537,181 )
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	5	9/12/2019	COMPETING CONTINUATION	$537,434
2019	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	4	6/10/2019	NON-COMPETING CONTINUATION	-$253
														Subtotal = $537,181

Issue Date FY: 2017 ( Subtotal = $522,850 )
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	4	6/20/2017	NON-COMPETING CONTINUATION	$52,285
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	4	3/15/2017	NON-COMPETING CONTINUATION	$470,565
														Subtotal = $522,850

Issue Date FY: 2016 ( Subtotal = $522,850 )
2016	2016	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	3	2/29/2016	NON-COMPETING CONTINUATION	$522,850
														Subtotal = $522,850

Issue Date FY: 2015 ( Subtotal = $523,542 )
2015	2015	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	2	2/25/2015	NON-COMPETING CONTINUATION	$523,542
														Subtotal = $523,542

Issue Date FY: 2014 ( Subtotal = $549,374 )
2014	2014	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	1	1/29/2014	NEW	$549,374
														Subtotal = $549,374

Grand Total All Awards = $5,484,099

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Inflammation Phenotypes in Pediatric Sepsis Induced Multiple Organ Failure Renewal

Award Number: R01GM108618

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: 03/01/2014

PERIOD OF PERFORMANCE END DATE: 06/30/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer