Wednesday, July 2, 2025 7/2/2025

Elucidating the relationship between lipid droplets, lipid metabolism, and lipotoxicity

Award Number: R01GM112948
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: 12/01/2014
PERIOD OF PERFORMANCE END DATE: 11/30/2024

Group Awards By:

View Award Description

Elucidating the relationship between lipid droplets, lipid metabolism, and lipotoxicity - Ferroptosis is a regulated form of lipotoxic cell death that involves iron-dependent generation of reactive oxygen species (ROS) and the accumulation of oxidatively damaged lipids (e.g. lipid peroxides). Ferroptosis has been implicated in the etiology of degenerative diseases, such as neurodegeneration associated with iron accumulation. Cells contain a protective pathway in which the glutathione-dependent peroxidase GPX4 repairs lipid peroxides and blocks cell death. Targeted induction of ferroptosis by inhibiting GPX4 has proven to be an efficacious treatment in in vitro and in vivo models of cancer, including drug-resistant forms of cancer. Despite the excitement from these recent findings, our understanding of the mechanisms underlying ferroptosis remains limited. Furthermore, many cancer cells are resistant to ferroptosis and the mechanisms of ferroptosis resistance in cancer remains mostly unknown. To overcome this critical gap in knowledge, we performed a synthetic lethal, whole-genome CRISPR screen to identify factors that protect cancer cells from ferroptosis. Our findings identify the lipid droplet oxidoreductase AIFM2 as a key factor that promotes ferroptosis resistance in cancer. Deletion of AIFM2 dramatically sensitizes cells to ferroptosis and AIFM2 levels correlate with cancer resistance across hundreds of cancer lines, indicating that AIFM2 is a biomarker of ferroptosis resistance and suggesting that it is broadly involved in ferroptosis resistance across many types of cancer. Our proposed research builds on our discovery and employs a combination of functional genomic, cell biology, and biochemistry strategies to achieve the following goals: 1) elucidate the mechanism by which AIFM2 prevents lipid damage and ferroptosis, 2) define the relationship between lipid droplets, fatty acid metabolism, and ferroptosis, and 3) identify new factors involved in protecting cancer cells from ferroptosis. These goals are potentially transformative because they focus on new mechanisms of ferroptosis resistance in cancer cells that act in parallel to the canonical glutathione-based protective system.


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 = -$12 )
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	10	4/16/2025	NON-COMPETING CONTINUATION	-$12
														Subtotal = -$12

Issue Date FY: 2024 ( Subtotal = $318,505 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	001	10	6/25/2024	NON-COMPETING CONTINUATION	$31,851
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	10	11/17/2023	NON-COMPETING CONTINUATION	$286,654
														Subtotal = $318,505

Issue Date FY: 2023 ( Subtotal = $318,595 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	001	9	2/16/2023	NON-COMPETING CONTINUATION	$31,860
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	9	11/18/2022	NON-COMPETING CONTINUATION	$286,735
														Subtotal = $318,595

Issue Date FY: 2022 ( Subtotal = $318,638 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	8	11/23/2021	NON-COMPETING CONTINUATION	$286,774
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	001	8	8/2/2022	NON-COMPETING CONTINUATION	$31,864
														Subtotal = $318,638

Issue Date FY: 2021 ( Subtotal = $317,038 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	7	10/28/2020	NON-COMPETING CONTINUATION	$285,333
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	001	7	2/23/2021	NON-COMPETING CONTINUATION	$31,705
														Subtotal = $317,038

Issue Date FY: 2020 ( Subtotal = $313,586 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	6	12/10/2019	COMPETING CONTINUATION	$313,586
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	002	6	8/30/2020	COMPETING CONTINUATION	$8
2020	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	001	5	8/30/2020	NON-COMPETING CONTINUATION	-$8
														Subtotal = $313,586

Issue Date FY: 2019 ( Subtotal = $292,071 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Biomedical Research and Research Training	000	5	11/19/2018	NON-COMPETING CONTINUATION	$292,071
														Subtotal = $292,071

Issue Date FY: 2018 ( Subtotal = $292,994 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Biomedical Research and Research Training	000	4	11/7/2017	NON-COMPETING CONTINUATION	$263,694
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Biomedical Research and Research Training	001	4	5/24/2018	NON-COMPETING CONTINUATION	$29,300
														Subtotal = $292,994

Issue Date FY: 2017 ( Subtotal = $293,833 )
2017	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Biomedical Research and Research Training	000	3	11/8/2016	NON-COMPETING CONTINUATION	$264,449
2017	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Biomedical Research and Research Training	001	3	8/11/2017	NON-COMPETING CONTINUATION	$29,384
														Subtotal = $293,833

Issue Date FY: 2016 ( Subtotal = $294,596 )
2016	2016	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Biomedical Research and Research Training	000	2	11/10/2015	NON-COMPETING CONTINUATION	$265,136
2016	2016	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Biomedical Research and Research Training	001	2	2/22/2016	NON-COMPETING CONTINUATION	$29,460
														Subtotal = $294,596

Issue Date FY: 2015 ( Subtotal = $294,764 )
2015	2015	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Biomedical Research and Research Training	000	1	11/19/2014	NEW	$294,764
														Subtotal = $294,764

Grand Total All Awards = $3,054,608

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Elucidating the relationship between lipid droplets, lipid metabolism, and lipotoxicity

Award Number: R01GM112948

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: 12/01/2014

PERIOD OF PERFORMANCE END DATE: 11/30/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer