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Generation of novel histoculture methods for studying human NK cell development

Award Number: R03AI156372
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: 12/01/2020
PERIOD OF PERFORMANCE END DATE: 11/30/2023

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Generation of novel histoculture methods for studying human NK cell development - Human natural killer (NK) cells play a critical role in the control of viral infection, particularly herpesviral infections such as Epstein-Barr virus (EBV). Their primary function of killing of virally infected target cells is mediated by the contact-dependent lysis through directed secretion of perforin and granzymes. Despite the demonstrated importance of their development and function, our understanding of how NK cells interact with other cells within tissue is limited by a lack of satisfying models for studying human immunity live and in situ. Significant challenges arise when trying to visualize cells within tissue, however it is highly relevant to human disease to find ways to better define how particularly innate immune cells migrate and exert their cytotoxic function. Our previous research has used 2D cell culture systems to define the importance of cell migration in human NK cell development. In this application, we propose the adoption of previously methods of secondary lymphoid tissue (tonsil) histoculture as a model to study human NK cell migration and function within an in vivolike tissue microenvironment using fast, low-toxicity imaging. We will combine our expertise in human developmental immunology with our technical skills in cutting-edge microscopy and image analysis to visualize human NK cells within autologous tissue and measure migration in 3 dimensions. We will additionally use multi-parametric imaging mass cytometry to localize cells within tissue (Aim 1). Further, we will extend our model to include infection of the tonsils with EBV, which will allow us to measure differences in cell migration and function between infected and uninfected tissue. By integrating infection of tissue histoculture with human EBV we will enable the study of human NK cells killing physiologically relevant targets within tissue (Aim 2). The generation of this novel model will advance future studies of human immunity and enable unprecedented insight into the behavior of immune cells within their tissue microenvironment.


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 = $0 )
2024	2022	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	000	2	7/24/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
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	Allergy and Infectious Diseases Research	000	2	2/1/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $81,000 )
2022	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	Allergy and Infectious Diseases Research	000	2	11/19/2021	NON-COMPETING CONTINUATION	$81,000
2022	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	Allergy and Infectious Diseases Research	001	2	1/13/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $81,000

Issue Date FY: 2021 ( Subtotal = $81,000 )
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	12/1/2020	NEW	$81,000
														Subtotal = $81,000

Grand Total All Awards = $162,000

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Generation of novel histoculture methods for studying human NK cell development

Award Number: R03AI156372

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: 12/01/2020

PERIOD OF PERFORMANCE END DATE: 11/30/2023

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