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Modeling early SARS-CoV-2 pathogenesis in human lung organoids and slice cultures

Award Number: K08AI163369
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/01/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2024

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Modeling early SARS-CoV-2 pathogenesis in human lung organoids and slice cultures - PROJECT SUMMARY COVID-19 remains an ongoing global health crisis, in part due to emerging variants. Fundamental questions remain about the mechanisms by which SARS-CoV-2 infection drives inflammation in the lower lung, in part due to the lack of in vitro infection models. Better understanding of variant biology and the immune pathways involved in early SARS-CoV-2 infection could offer insights for the development of novel therapeutic strategies. The antiviral cytokines type I interferons and their downstream effects have been implicated in COVID-19. SARS-CoV-2 may inhibit or promote interferon effects in some cell types in the lung, and this may differ between viral variants. My preliminary work shows that organoids and lung slice cultures can be used to study these early events in SARS-CoV-2 infection and identifies macrophages as a cell type that activates the interferon pathway in infected cultures. Thus, I propose using quantitative PCR, single-cell RNA sequencing, and flow cytometry to study viral variants and to deeply profile the changes to viral and host gene and protein expression during infection. I will study highly relevant cell types that can interact with each other in a similar fashion to the in vivo lung. I will study the interferon stimulated gene response and identify the cell types in which it is being modulated or would be good targets for therapeutic intervention. This knowledge will be critical to our efforts to combat the COVID-19 pandemic. I am currently a fellow in Dr. Catherine Blish’s lab in the Division of Infectious Diseases at Stanford University and I am in the process of being promoted to a full time Instructor position. Stanford University offers an outstanding scientific environment, where all the resources necessary to the success of this project are made available to me. My long-term goal is to become an independent physician-scientist, with a research focus in respiratory viral pathogenesis. I aim to establish a research program focused on modeling established and emerging infections in primary lung tissue with a goal of developing new treatments. To achieve this goal, I have designed a tailored career development plan that comprises both formal and informal training. This training will enhance my expertise in lung biology, immunology, and sequencing analysis. Informal training in these topics will be provided by my mentor, Dr. Catherine Blish, and by the rest of my advisory committee, Dr. Calvin Kuo, Dr. Mark Krasnow, Dr. Susan Holmes, and Dr. Ben Pinsky. With their guidance, I will complete the proposed project, submit research manuscripts, obtain further funding, and obtain an independent research position.


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 = $192,509 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	5	1/10/2025	NON-COMPETING CONTINUATION	$192,509
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	003	4	2/14/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$50,064
2025	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	002	3	2/14/2025	NON-COMPETING CONTINUATION	-$17,810
2025	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	001	2	2/14/2025	NON-COMPETING CONTINUATION	-$32,254
														Subtotal = $192,509

Issue Date FY: 2024 ( Subtotal = $193,320 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	001	3	4/26/2024	NON-COMPETING CONTINUATION	-$175,510
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	3	1/9/2024	NON-COMPETING CONTINUATION	$193,320
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	002	4	4/26/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$175,510
														Subtotal = $193,320

Issue Date FY: 2023 ( Subtotal = $193,320 )
2023	2023	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	2	1/20/2023	NON-COMPETING CONTINUATION	$193,320
														Subtotal = $193,320

Issue Date FY: 2022 ( Subtotal = $193,320 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	1	1/28/2022	NEW	$193,320
														Subtotal = $193,320

Grand Total All Awards = $772,469

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Modeling early SARS-CoV-2 pathogenesis in human lung organoids and slice cultures

Award Number: K08AI163369

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/01/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2024

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