Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

A Pathway of Tumor Suppression

Award Number: R01CA047296
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/1988
PERIOD OF PERFORMANCE END DATE: 04/30/2027

Group Awards By:

View Award Description

A Pathway of Tumor Suppression - Abstract The p53 tumor suppressor is a DNA damage/stress response protein that functions as a transcription factor to regulate a large repertoire of genes that prevent proliferation of damaged cells via initiation of cell cycle arrest and senescent programs or via apoptosis and other mechanisms of cell death. However, the molecular, morphological, and physiological consequences of this transcriptional program remain poorly understood in vivo. We have defined the physiological p53 transcriptional program using the mouse as a model system. Global p53 activation causes anomalies in the pancreas (an acinar to ductal metaplasia), intestine (crypt atrophy) and kidney (dilated tubules), and directly activates hundreds of genes many in a tissue-specific manner. Seven genes, however, are universally expressed in the five tissues (pancreas, intestine, kidney, ovary, heart) examined and represent a pan-tissue p53 transcriptional signature which includes Mdm2 (which encodes a potent p53 inhibitor) but not p21 (a cell cycle inhibitor and first identified p53 target gene). The pan-tissue p53 transcriptional signature includes three other genes with central functions in cell survival or cell death for which little is known. Eda2r is a transmembrane receptor and member of the TNF family with the ability to induce apoptosis. Significantly reduced expression of EDA2R is observed in mutant p53 breast, colorectal, and lung cancers and in pancreatic ductal adenocarcinoma and glioblastoma. Gtse1 encodes a cytoplasmic protein that migrates to the nucleus upon DNA damage, and binds and inhibits p53 activity in cells in culture. A review of cancer sequencing data indicates that amplification of GTSE1 is mutually exclusive with TP53 alterations in angiosarcomas further implicating it as an inhibitor of p53 function. Polκ is an error prone DNA polymerase that allows replication of damaged DNA and ensures cell survival, but contributes to an increased mutation burden. We hypothesize that these three transcriptional targets are key effectors of the p53 pathway and functionally contribute to ensure cell survival (via cell cycle arrest or senescence) or initiate cell death. In addition, two of these effectors have opposing properties: Eda2r induces apoptosis, while Gtse1 inhibits p53 activity and ensures cell survival. Single cell analysis in the pancreas upon p53 activation, either by deletion of Mdm2 or inflammation, will be performed to understand the cell-specific and dynamic nature of the p53 transcriptional program. The specific aims are: 1) to determine the roles of Eda2r in p53-dependent processes in vivo; 2) To determine the importance of Gtse1 in inhibiting p53 activity in vivo; 3) To determine the functional significance of p53 regulation of Polκ in homeostasis, inflammation and cancer; and 4) To determine the specificity of the p53 response using single cell analyses of the pancreas. A deep fundamental knowledge of the physiological p53 transcriptional program and individual cellular outcomes is essential to maximize the efficacy of p53 activation therapies and may reveal novel therapeutic strategies.


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 = $466,560 )
2026	2026	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	38	3/26/2026	NON-COMPETING CONTINUATION	$466,560
														Subtotal = $466,560

Issue Date FY: 2025 ( Subtotal = $466,560 )
2025	2025	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	37	4/2/2025	NON-COMPETING CONTINUATION	$419,904
2025	2025	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	37	5/23/2025	NON-COMPETING CONTINUATION	$46,656
														Subtotal = $466,560

Issue Date FY: 2024 ( Subtotal = $443,233 )
2024	2024	THE UNIVERISTY OF TEXAS MD ANDERSON CANCER CENTER, A COMPONENT OF THE UNIVERISTY OF TEXAS SYSTEM	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	36	4/8/2024	NON-COMPETING CONTINUATION	$443,233
														Subtotal = $443,233

Issue Date FY: 2023 ( Subtotal = $466,560 )
2023	2023	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	002	35	5/1/2023	NON-COMPETING CONTINUATION	$466,560
2023	2022	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	34	4/26/2023	COMPETING CONTINUATION	$162,579
2023	2021	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	33	4/26/2023	NON-COMPETING CONTINUATION	-$162,579
														Subtotal = $466,560

Issue Date FY: 2022 ( Subtotal = $466,560 )
2022	2022	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	34	6/21/2022	COMPETING CONTINUATION	$466,560
2022	2021	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	33	6/13/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $466,560

Issue Date FY: 2021 ( Subtotal = $366,000 )
2021	2021	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	33	2/5/2021	NON-COMPETING CONTINUATION	$18,301
2021	2021	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	33	11/13/2020	NON-COMPETING CONTINUATION	$347,699
														Subtotal = $366,000

Issue Date FY: 2020 ( Subtotal = $366,000 )
2020	2020	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	32	1/13/2020	NON-COMPETING CONTINUATION	$36,600
2020	2020	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	32	11/6/2019	NON-COMPETING CONTINUATION	$329,400
														Subtotal = $366,000

Issue Date FY: 2019 ( Subtotal = $355,019 )
2019	2019	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	31	11/19/2018	NON-COMPETING CONTINUATION	$355,019
														Subtotal = $355,019

Issue Date FY: 2018 ( Subtotal = $366,000 )
2018	2018	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	30	5/23/2018	NON-COMPETING CONTINUATION	$36,600
2018	2018	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	30	11/21/2017	NON-COMPETING CONTINUATION	$329,400
														Subtotal = $366,000

Issue Date FY: 2017 ( Subtotal = $366,000 )
2017	2017	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	29	12/22/2016	COMPETING CONTINUATION	$366,000
2017	2016	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	28	3/31/2017	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $366,000

Issue Date FY: 2016 ( Subtotal = $249,580 )
2016	2016	UNIV OF TEXAS SYS CANCER CTR, M D ANDERSON HOSP/TUM INS	1515 HOLCOMBE BLVD, ROOM 202	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	28	2/17/2016	EXTENSION WITH OR WITHOUT FUNDS	$24,959
2016	2016	UNIV OF TEXAS SYS CANCER CTR, M D ANDERSON HOSP/TUM INS	1515 HOLCOMBE BLVD, ROOM 202	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	28	11/12/2015	EXTENSION WITH OR WITHOUT FUNDS	$224,621
														Subtotal = $249,580

Issue Date FY: 2015 ( Subtotal = $249,580 )
2015	2015	UNIV OF TEXAS SYS CANCER CTR, M D ANDERSON HOSP/TUM INS	1515 HOLCOMBE BLVD, ROOM 202	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	27	11/12/2014	NON-COMPETING CONTINUATION	$224,621
2015	2015	UNIV OF TEXAS SYS CANCER CTR, M D ANDERSON HOSP/TUM INS	1515 HOLCOMBE BLVD, ROOM 202	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	27	1/23/2015	NON-COMPETING CONTINUATION	$24,959
														Subtotal = $249,580

Issue Date FY: 2014 ( Subtotal = $242,092 )
2014	2014	UNIV OF TEXAS SYS CANCER CTR, M D ANDERSON HOSP/TUM INS	1515 HOLCOMBE BLVD, ROOM 202	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	26	11/8/2013	NON-COMPETING CONTINUATION	$224,622
2014	2014	UNIV OF TEXAS SYS CANCER CTR, M D ANDERSON HOSP/TUM INS	1515 HOLCOMBE BLVD, ROOM 202	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	26	4/16/2014	NON-COMPETING CONTINUATION	$17,470
														Subtotal = $242,092

Issue Date FY: 2013 ( Subtotal = $234,605 )
2013	2013	UNIV OF TEXAS SYS CANCER CTR, M D ANDERSON HOSP/TUM INS	1515 HOLCOMBE BLVD, ROOM 202	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	25	5/13/2013	NON-COMPETING CONTINUATION	$109,815
2013	2013	UNIV OF TEXAS SYS CANCER CTR, M D ANDERSON HOSP/TUM INS	1515 HOLCOMBE BLVD, ROOM 202	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	25	11/20/2012	NON-COMPETING CONTINUATION	$124,790
														Subtotal = $234,605

Issue Date FY: 2012 ( Subtotal = $249,580 )
2012	2012	UNIV OF TEXAS SYS CANCER CTR, M D ANDERSON HOSP/TUM INS	1515 HOLCOMBE BLVD, ROOM 202	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	24	4/30/2012	COMPETING CONTINUATION	$49,915
2012	2012	UNIV OF TEXAS SYS CANCER CTR, M D ANDERSON HOSP/TUM INS	1515 HOLCOMBE BLVD, ROOM 202	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	24	12/13/2011	COMPETING CONTINUATION	$199,665
														Subtotal = $249,580

Issue Date FY: 2010 ( Subtotal = $236,943 )
2010	2010	UNIV OF TEXAS SYS CANCER CTR, M D ANDERSON HOSP/TUM INS	1515 HOLCOMBE BLVD, ROOM 202	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	23	5/4/2010	NON-COMPETING CONTINUATION	$236,943
														Subtotal = $236,943

Issue Date FY: 2009 ( Subtotal = $236,943 )
2009	2009	UNIV OF TEXAS SYS CANCER CTR, M D ANDERSON HOSP/TUM INS	1515 HOLCOMBE BLVD, ROOM 202	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	22	5/6/2009	NON-COMPETING CONTINUATION	$236,943
														Subtotal = $236,943

Issue Date FY: 2008 ( Subtotal = $236,943 )
2008	2008	UNIV OF TEXAS SYS CANCER CTR, M D ANDERSON HOSP/TUM INS	1515 HOLCOMBE BLVD, ROOM 202	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	21	5/30/2008	NON-COMPETING CONTINUATION	$236,943
														Subtotal = $236,943

Issue Date FY: 2007 ( Subtotal = $236,943 ) (Continued on the next page)
Grand Total All Awards = $8,496,044

Page 1 of 2 (69 items)12

Top

All Categories

About

Search

Reports

Data Submission

Award Information

A Pathway of Tumor Suppression

Award Number: R01CA047296

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/1988

PERIOD OF PERFORMANCE END DATE: 04/30/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer