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Characterizing the Regulation of Ferroptosis

Award Number: R01GM122923
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: 09/05/2017
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Characterizing the Regulation of Ferroptosis - Project Summary/Abstract Ferroptosis is a non-apoptotic cell death process that can suppress tumor formation and contribute to disease pathology. The long-term objective of this research is to understand the molecular regulation of ferroptosis. Ferroptosis is thought to occur through a stereotypical and invariant lipid-dependent mechanism. However, in new preliminary studies we have uncovered evidence for two different forms of ferroptosis defined by unique genetic regulation and metabolic alterations. We find that ferroptosis triggered by direct inactivation of the enzyme GPX4 requires the function of the lipid metabolic enzyme ACSL4. A second sub-type of ferroptosis, triggered by cystine deprivation, does not require ACSL4 or related lipid metabolic enzymes and instead relies on a novel set of genes. Guided by these new preliminary data, our central hypothesis is that ferroptosis can be executed by two fundamentally distinct mechanisms. We will test this hypothesis by pursuing three specific aims: (i) defining the role of ACSL4 and related lipid metabolic enzymes in promoting ferroptosis in response to direct GPX4 inhibition, (ii) identifying cellular and molecular features that distinguish the two ferroptosis mechanisms in vitro and in vivo, and (iii) defining genes and processes that regulate ACSL4-independent ferroptosis in response to cystine deprivation. These studies will be carried out using cutting-edge chemical, genetic, functional genomic, lipidomic, and imaging tools and methods. This research will advance our fundamental understanding of ferroptosis, with the ultimate goal of improving human health.


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: 2026 ( Subtotal = $340,452 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	9	2/12/2026	NON-COMPETING CONTINUATION	$340,452
														Subtotal = $340,452

Issue Date FY: 2025 ( Subtotal = $340,452 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	8	4/11/2025	NON-COMPETING CONTINUATION	$340,452
														Subtotal = $340,452

Issue Date FY: 2024 ( Subtotal = $435,703 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	004	7	6/25/2024	NON-COMPETING CONTINUATION	$33,643
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	003	7	1/30/2024	NON-COMPETING CONTINUATION	$302,780
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	005	7	9/6/2024	SUPPLEMENT FOR EXPANSION	$99,280
2024	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	002	6	12/5/2023	COMPETING CONTINUATION	$34,442
2024	2021	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	001	5	12/5/2023	SUPPLEMENT FOR EXPANSION	-$13,410
2024	2021	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	5	12/5/2023	NON-COMPETING CONTINUATION	-$21,032
														Subtotal = $435,703

Issue Date FY: 2023 ( Subtotal = $337,295 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	001	6	4/3/2023	COMPETING CONTINUATION	$337,295
2023	2021	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	5	3/24/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $337,295

Issue Date FY: 2021 ( Subtotal = $539,921 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	4	12/23/2020	SUPPLEMENT FOR EXPANSION	$84,185
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	001	5	9/2/2021	NON-COMPETING CONTINUATION	$329,700
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	002	5	9/3/2021	SUPPLEMENT FOR EXPANSION	$126,036
														Subtotal = $539,921

Issue Date FY: 2020 ( Subtotal = $329,267 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	4	8/19/2020	NON-COMPETING CONTINUATION	$329,267
														Subtotal = $329,267

Issue Date FY: 2019 ( Subtotal = $328,671 )
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	3	8/14/2019	NON-COMPETING CONTINUATION	$328,671
														Subtotal = $328,671

Issue Date FY: 2018 ( Subtotal = $390,291 )
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	001	2	9/6/2018	SUPPLEMENT FOR EXPANSION	$62,200
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	2	8/31/2018	NON-COMPETING CONTINUATION	$328,091
														Subtotal = $390,291

Issue Date FY: 2017 ( Subtotal = $327,529 )
2017	2017	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	1	9/5/2017	NEW	$327,529
														Subtotal = $327,529

Grand Total All Awards = $3,369,581

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Characterizing the Regulation of Ferroptosis

Award Number: R01GM122923

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: 09/05/2017

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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