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Regulation of memory CD8 T cell development

Award Number: R37AI066232
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2005
PERIOD OF PERFORMANCE END DATE: 01/31/2023

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Regulation of memory CD8 T cell development - During infection the adaptive immune response has two primary goals, a short-term goal to eradicate the present infection and a long-term goal to establish immunological memory and protect against re- infection. These two goals are fulfilled by generating a heterogeneous pool of activated T and B cells that contain both short-term effector cells and memory cell precursors that persist long-term to seed a + pool of memory cells and provide exceptional protection agianst reinfection. Because cytotoxic CD8 T lymphocyte (CTL) responses are critical for clearing many types of intracellular infections and tumors, the development of many vaccines (e.g., HIV and plasmodium) are aimed at generating protective memory CD8 T cells. The question of how different types of memory T cells form during infection and vaccination and what genetic pathways and epigenetic changes control this process remains paramount. This past decade represents the dawn of a molecular understanding of memory CD8 T cell development, which largely through the use of well-characterized infection models in mice has discovered critical transcription factors and cytokine signaling pathways involved in this process. This work has delivered unprecedented insight into the genetic pathways that control memory T cell differentiation, but we are still in a discovery phase as only a handful of factors (cytokines and transcription factors (TFs)) have been identified that modulate effector and memory CD8 T cell differentiation in vivo during infection. Moreover, it is unclear how such factors cooperate or combat one another activities or to regulate the epigenetic states that specify effector and memory T cell fates. Elucidating these genetic and epigenetic networks is necessary to understand how the effector and memory T cell differentiation is controlled. It is likely that we will only really start to understand how T cell fates are specified and how the inherent heterogeneity and plasticity observed in T cells is controlled through studying the epigenome of T cells. Thus, the overarching goals of this MERIT extension are to elucidate genetic and epigenetic control of effector and memory CD8 T cell differentiation, plasticity and heterogeneity. This proposal will not only provide new insight on novel genetic regulators of effector and memory T cell development, but it will also reveal how effector T cell plasticity or commitment to terminal fates is regulated at the genomic level. RELEVANCE (See instructions):


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 = $0 )
2023	2022	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	18	9/18/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $994,157 )
2022	2022	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	18	7/21/2022	SUPPLEMENT FOR EXPANSION	$416,957
2022	2022	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	18	1/27/2022	NON-COMPETING CONTINUATION	$577,200
														Subtotal = $994,157

Issue Date FY: 2021 ( Subtotal = $577,200 )
2021	2021	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	17	1/5/2021	NON-COMPETING CONTINUATION	$577,200
														Subtotal = $577,200

Issue Date FY: 2020 ( Subtotal = $577,200 )
2020	2020	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	16	1/31/2020	NON-COMPETING CONTINUATION	$577,200
														Subtotal = $577,200

Issue Date FY: 2019 ( Subtotal = $577,200 )
2019	2019	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	15	4/22/2019	NON-COMPETING CONTINUATION	$577,200
														Subtotal = $577,200

Issue Date FY: 2018 ( Subtotal = $577,200 )
2018	2018	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	14	2/16/2018	EXTENSION WITH OR WITHOUT FUNDS	$577,200
2018	2017	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Allergy and Infectious Diseases Research	001	13	7/11/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $577,200

Issue Date FY: 2017 ( Subtotal = $416,250 )
2017	2017	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Allergy and Infectious Diseases Research	000	13	1/18/2017	NON-COMPETING CONTINUATION	$416,250
														Subtotal = $416,250

Issue Date FY: 2016 ( Subtotal = $416,250 )
2016	2016	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Allergy and Infectious Diseases Research	000	12	1/26/2016	EXTENSION WITH OR WITHOUT FUNDS	$416,250
														Subtotal = $416,250

Issue Date FY: 2015 ( Subtotal = $416,250 )
2015	2015	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Allergy and Infectious Diseases Research	000	11	1/22/2015	NON-COMPETING CONTINUATION	$416,250
														Subtotal = $416,250

Issue Date FY: 2014 ( Subtotal = $416,250 )
2014	2014	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Allergy and Infectious Diseases Research	000	10	1/9/2014	NON-COMPETING CONTINUATION	$374,625
2014	2014	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Allergy and Infectious Diseases Research	001	10	6/5/2014	NON-COMPETING CONTINUATION	$41,625
														Subtotal = $416,250

Issue Date FY: 2013 ( Subtotal = $390,785 )
2013	2013	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Allergy and Infectious Diseases Research	001	9	6/11/2013	COMPETING CONTINUATION	$16,629
2013	2013	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Allergy and Infectious Diseases Research	002	9	7/15/2013	COMPETING CONTINUATION	$0
2013	2013	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Allergy and Infectious Diseases Research	000	9	1/22/2013	COMPETING CONTINUATION	$374,156
														Subtotal = $390,785

Grand Total All Awards = $5,358,742

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Regulation of memory CD8 T cell development

Award Number: R37AI066232

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2005

PERIOD OF PERFORMANCE END DATE: 01/31/2023

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