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Mouse models to discover new drivers of medulloblastoma

Award Number: R01CA159859
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Medulloblastoma (MB) is the most common malignant brain tumor in children. Although aggressive treatments have improved outcomes, many MB patients still die of their disease, and survivors suffer severe long-term side effects from the therapy. Thus, an increased understanding of the disease and improved therapeutic approaches are critical. MB is comprised of four subgroups – WNT, Sonic hedgehog (SHH), Group 3 and Group 4 – that differ in terms of genetics, epigenetics, clinical characteristics and outcomes. Although we have some mechanistic understanding of WNT, SHH and Group 3 tumors, the genes and pathways that underlie Group 4, the most prevalent form of the disease, remain a mystery. Identifying oncogenic drivers and using them to create animal models of Group 4 MB is critical for development and testing of new therapies. Our analysis of the genome and epigenome of >400 human Group 4 MBs has identified single nucleotide variants (SNVs) as well as chromosomal copy number alterations (CNAs). While these studies have generated lists of candidate drivers, none of these has been tested or proven necessary or sufficient to initiate tumor growth. We hypothesize that perturbing expression of candidate genes or CNAs in neural progenitors will generate models of Group 4 MB, thereby validating their functional importance. To test this hypothesis, we propose to knock out or overexpress genes in murine and human (iPS-derived) neural progenitors and evaluate tumorigenic potential in vivo. These studies will create robust models of Group 4 MB that can be used to study tumor biology and to identify novel approaches to therapy.


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: 2023 ( Subtotal = $706,017 )
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Cause and Prevention Research	003	13	9/15/2023	NON-COMPETING CONTINUATION	$14,121
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Cause and Prevention Research	002	13	9/1/2023	NON-COMPETING CONTINUATION	$691,896
2023	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Cause and Prevention Research	001	12	5/17/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$643,914
2023	2022	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	11	5/17/2023	COMPETING CONTINUATION	-$643,914
														Subtotal = $706,017

Issue Date FY: 2022 ( Subtotal = $803,132 )
2022	2022	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	001	11	9/1/2022	COMPETING CONTINUATION	$803,132
2022	2021	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	10	6/7/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $803,132

Issue Date FY: 2021 ( Subtotal = $746,845 )
2021	2021	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	10	1/26/2021	NON-COMPETING CONTINUATION	$746,845
														Subtotal = $746,845

Issue Date FY: 2020 ( Subtotal = $746,845 )
2020	2020	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	9	1/16/2020	NON-COMPETING CONTINUATION	$746,845
														Subtotal = $746,845

Issue Date FY: 2019 ( Subtotal = $724,440 )
2019	2019	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	8	2/4/2019	NON-COMPETING CONTINUATION	$724,440
														Subtotal = $724,440

Issue Date FY: 2018 ( Subtotal = $746,845 )
2018	2018	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	001	7	5/23/2018	NON-COMPETING CONTINUATION	$74,684
2018	2018	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	7	1/16/2018	NON-COMPETING CONTINUATION	$672,161
														Subtotal = $746,845

Issue Date FY: 2017 ( Subtotal = $794,344 )
2017	2017	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	001	6	3/2/2017	COMPETING CONTINUATION	$153,750
2017	2017	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	6	1/30/2017	COMPETING CONTINUATION	$640,594
														Subtotal = $794,344

Issue Date FY: 2015 ( Subtotal = $617,747 )
2015	2015	SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE	10901 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	5	3/11/2015	NON-COMPETING CONTINUATION	$617,747
														Subtotal = $617,747

Issue Date FY: 2014 ( Subtotal = $599,474 )
2014	2014	SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE	10901 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	4	5/6/2014	NON-COMPETING CONTINUATION	$599,474
														Subtotal = $599,474

Issue Date FY: 2013 ( Subtotal = $581,217 )
2013	2013	SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE	10901 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	001	3	7/3/2013	NON-COMPETING CONTINUATION	$302,975
2013	2013	SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE	10901 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	3	3/12/2013	NON-COMPETING CONTINUATION	$278,242
														Subtotal = $581,217

Issue Date FY: 2012 ( Subtotal = $618,678 )
2012	2012	SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE	10901 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	2	4/4/2012	NON-COMPETING CONTINUATION	$618,678
														Subtotal = $618,678

Issue Date FY: 2011 ( Subtotal = $640,572 )
2011	2011	SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE	10901 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Cause and Prevention Research	000	1	4/4/2011	NEW	$640,572
														Subtotal = $640,572

Grand Total All Awards = $8,326,156

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Mouse models to discover new drivers of medulloblastoma

Award Number: R01CA159859

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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