Thursday, November 21, 2024 11/21/2024

Autophagy-mediated defense against inflammation and cancer

Award Number: R01CA140964
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Mounting evidence from our laboratory and others suggests that a lysosomal degradation pathway, called autophagy, plays a central role in orchestrating inflammation and cancer biology. Recently, our laboratory generated UVRAG (UV irradiation resistance associated gene) mutant mice that show normal levels of basal autophagy but are deficient in stimulus-induced autophagy. With this mouse model, we demonstrate that autophagy dysregulation could exacerbate inflammation and promote spontaneous cancers. However, major gaps still exist in our understanding of intricate relationship between autophagy, inflammation and cancer, including 1) what are the mechanisms by which inadequate autophagy perpetuates inflammasome response and drives inflammation-associated pathologies? and 2) how does basal autophagy suppression affect tissue homeostasis and promote cancer susceptibility? This project will fill these gaps by focusing on two Specific Aims, including 1) investigating molecular mechanism of autophagy dysfunction on inflammatory signaling and inflammation-associated pathologies; and 2) identifying molecular mechanism of autophagy inhibition in Wnt/b- catenin signaling activation and spontaneous tumorigenesis. These aims will be addressed using multidisciplinary innovative approaches that integrate state-of-the-art genetic, biochemistry, single cell analysis, and physiological assays in cells, 3D organoid culture, and mice with targeted mutations in genes related to UVRAG function and autophagy deregulation. Together, we anticipate that these studies will elucidate the mechanisms underlying the intricate dialog between imbalance of autophagy, uncontrolled inflammation, and spontaneous tumorigenesis, thereby providing important new insights into the functional repertoire of autophagy and facilitating the development of much-needed new strategies for the treatment of inflammatory pathologies and cancer, particularly those associated with autophagy defects.


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: 2024 ( Subtotal = $412,961 )
2024	2024	THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	000	15	6/12/2024	NON-COMPETING CONTINUATION	$412,961
														Subtotal = $412,961

Issue Date FY: 2023 ( Subtotal = $434,696 )
2023	2023	THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	000	14	6/13/2023	NON-COMPETING CONTINUATION	$426,002
2023	2023	THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	001	14	9/15/2023	NON-COMPETING CONTINUATION	$8,694
														Subtotal = $434,696

Issue Date FY: 2022 ( Subtotal = $426,002 )
2022	2022	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	002	13	6/22/2022	NON-COMPETING CONTINUATION	$426,002
2022	2021	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	001	12	11/8/2021	COMPETING CONTINUATION	$19,074
2022	2019	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Cause and Prevention Research	000	11	11/8/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$19,074
														Subtotal = $426,002

Issue Date FY: 2021 ( Subtotal = $415,844 )
2021	2021	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	002	12	7/6/2021	COMPETING CONTINUATION	$415,844
2021	2019	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Cause and Prevention Research	000	11	1/11/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2021	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Cancer Cause and Prevention Research	001	10	1/19/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $415,844

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	10	8/31/2020	NON-COMPETING CONTINUATION	-$124,365
2020	2019	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Cause and Prevention Research	001	11	8/31/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$124,365
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $342,106 )
2019	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	10	12/4/2018	NON-COMPETING CONTINUATION	$342,106
														Subtotal = $342,106

Issue Date FY: 2018 ( Subtotal = $399,865 )
2018	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Cancer Cause and Prevention Research	002	9	9/10/2018	NON-COMPETING CONTINUATION	$47,177
2018	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER STREET THIRD FLOOR	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	9	12/18/2017	NON-COMPETING CONTINUATION	$317,419
2018	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER STREET THIRD FLOOR	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Cause and Prevention Research	001	9	5/23/2018	NON-COMPETING CONTINUATION	$35,269
														Subtotal = $399,865

Issue Date FY: 2017 ( Subtotal = $352,688 )
2017	2017	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER STREET THIRD FLOOR	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Cause and Prevention Research	001	8	6/7/2017	NON-COMPETING CONTINUATION	$35,269
2017	2017	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER STREET THIRD FLOOR	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	8	12/12/2016	NON-COMPETING CONTINUATION	$317,419
														Subtotal = $352,688

Issue Date FY: 2016 ( Subtotal = $352,688 )
2016	2016	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Cause and Prevention Research	001	7	2/22/2016	NON-COMPETING CONTINUATION	$35,269
2016	2016	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	7	12/17/2015	NON-COMPETING CONTINUATION	$317,419
														Subtotal = $352,688

Issue Date FY: 2015 ( Subtotal = $319,952 )
2015	2015	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Cause and Prevention Research	002	6	2/27/2015	COMPETING CONTINUATION	$16,840
2015	2015	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Cause and Prevention Research	001	6	12/5/2014	COMPETING CONTINUATION	$303,112
2015	2013	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Biology Research	000	5	11/21/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $319,952

Issue Date FY: 2013 ( Subtotal = $275,852 )
2013	2013	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Biology Research	000	5	7/5/2013	NON-COMPETING CONTINUATION	$275,852
														Subtotal = $275,852

Issue Date FY: 2012 ( Subtotal = $293,460 )
2012	2012	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Biology Research	000	4	7/12/2012	NON-COMPETING CONTINUATION	$293,460
														Subtotal = $293,460

Issue Date FY: 2011 ( Subtotal = $293,460 )
2011	2011	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Biology Research	000	3	7/1/2011	NON-COMPETING CONTINUATION	$293,460
														Subtotal = $293,460

Issue Date FY: 2010 ( Subtotal = $302,535 )
2010	2010	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Biology Research	000	2	7/19/2010	NON-COMPETING CONTINUATION	$302,535
														Subtotal = $302,535

Issue Date FY: 2009 ( Subtotal = $304,092 )
2009	2009	UNIVERSITY OF SOUTHERN CALIFORNIA	3500 SOUTH FIGUEROA STREET 102	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Biology Research	000	1	9/18/2009	NEW	$304,092
														Subtotal = $304,092

Grand Total All Awards = $4,926,201

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Autophagy-mediated defense against inflammation and cancer

Award Number: R01CA140964

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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