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Mechanistic Elucidation of Class Switch Recombination and Somatic Hypermutation

Award Number: R01AI072194
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT Upon encountering antigens, mature B cells express activation induced cytidine deaminase (AID) and undergo immunoglobulin heavy chain (Igh) class switch recombination (CSR) and somatic hypermutation (SHM). CSR proceeds through the obligate generation of DNA double strand breaks (DSBs), which constitute one of the most toxic lesions that can occur in a cell. A single unrepaired DSB can cause cell death or potentiate chromosomal translocations that are hallmarks of many types of cancer, including lymphomas. Thus, mechanisms that promote generation of DSBs and facilitate DSB repair are intergral to both immunity and preservation of genomic integrity. In this proposal we test the notion that single proteins can coordinate both DSB formation and mediate end-joining to efficiently generate and repair DSBs. We test the hypothesis that the nucleosomal remodeling protein CHD4 co-ordinates generation and repair of Igh DSBs (aim 1) and the C- terminus of AID mediates efficient DNA repair of Igh DSBs (aim 2). Successful completion of the experiments will have far reaching implications in our understanding of both B cell immunity and B cell lymphomas.


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 = $515,070 )
2025	2025	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	15	12/23/2024	NON-COMPETING CONTINUATION	$515,070
														Subtotal = $515,070

Issue Date FY: 2024 ( Subtotal = $531,000 )
2024	2024	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	14	1/5/2024	NON-COMPETING CONTINUATION	$477,900
2024	2024	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	001	14	5/24/2024	NON-COMPETING CONTINUATION	$53,100
														Subtotal = $531,000

Issue Date FY: 2023 ( Subtotal = $531,000 )
2023	2023	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	13	1/24/2023	NON-COMPETING CONTINUATION	$531,000
														Subtotal = $531,000

Issue Date FY: 2022 ( Subtotal = $531,000 )
2022	2022	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	12	1/14/2022	NON-COMPETING CONTINUATION	$531,000
														Subtotal = $531,000

Issue Date FY: 2021 ( Subtotal = $267,272 )
2021	2021	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	11	2/10/2021	COMPETING CONTINUATION	$267,272
2021	2019	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	001	10	7/19/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $267,272

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	10	8/16/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $439,750 )
2019	2019	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	10	10/24/2018	NON-COMPETING CONTINUATION	$439,750
														Subtotal = $439,750

Issue Date FY: 2018 ( Subtotal = $439,750 )
2018	2018	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	9	10/23/2017	NON-COMPETING CONTINUATION	$439,750
														Subtotal = $439,750

Issue Date FY: 2017 ( Subtotal = $439,750 )
2017	2017	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	8	10/25/2016	NON-COMPETING CONTINUATION	$439,750
														Subtotal = $439,750

Issue Date FY: 2016 ( Subtotal = $439,750 )
2016	2016	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	7	10/28/2015	NON-COMPETING CONTINUATION	$439,750
														Subtotal = $439,750

Issue Date FY: 2015 ( Subtotal = $438,958 )
2015	2015	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	001	6	11/4/2014	COMPETING CONTINUATION	$438,958
2015	2013	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10021	NEW YORK	USA	Allergy and Infectious Diseases Research	000	5	11/1/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $438,958

Issue Date FY: 2013 ( Subtotal = $436,694 )
2013	2013	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	5	8/1/2013	NON-COMPETING CONTINUATION	$436,694
														Subtotal = $436,694

Issue Date FY: 2012 ( Subtotal = $464,567 )
2012	2012	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	4	6/28/2012	NON-COMPETING CONTINUATION	$464,567
														Subtotal = $464,567

Issue Date FY: 2011 ( Subtotal = $464,567 )
2011	2011	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	3	6/16/2011	NON-COMPETING CONTINUATION	$464,567
														Subtotal = $464,567

Issue Date FY: 2010 ( Subtotal = $469,260 )
2010	2010	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	2	6/25/2010	NON-COMPETING CONTINUATION	$469,260
														Subtotal = $469,260

Issue Date FY: 2009 ( Subtotal = $474,000 )
2009	2009	SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	6/11/2009	NEW	$474,000
														Subtotal = $474,000

Grand Total All Awards = $6,882,388

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Mechanistic Elucidation of Class Switch Recombination and Somatic Hypermutation

Award Number: R01AI072194

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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