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Elucidating the roles of alveolar macrophage inflammation and self renewal during influenza infection

Award Number: R01AG069264
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2020
PERIOD OF PERFORMANCE END DATE: 04/30/2030

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Elucidating the roles of alveolar macrophage inflammation and self renewal during influenza infection - Summary Respiratory viral infections, such as influenza and SARS-CoV-2, pose significant public health challenges, particularly affecting older adults with severe outcomes and long-term health issues like Post-Acute Sequelae of SARS-CoV-2 (PASC). Alveolar macrophages (AMs), the primary macrophage population in the lungs, play crucial roles in lung defense and tissue repair, but can become pro-inflammatory during infections, leading to tissue damage. Our previous studies identified that TCF4 and β-catenin, key transcription factors in WNT signaling, have opposing effects on AM responses: TCF4 supports AM stem- like self-renewal, while β-catenin enhances inflammatory responses. Additionally, AMs from aged mice and humans exhibit senescence-like characteristics, likely contributing to adverse outcomes in the respiratory tract during aging. The aims of this grant are to elucidate the reciprocal regulation of TCF4 and β-catenin in dictating AM fate and function, and to investigate the roles of AM senescence, controlled by TCF4, in lung health and virus-associated acute and chronic diseases during aging. Furthermore, we aim to develop therapeutic strategies targeting TCF4 to treat age-related acute and chronic conditions following respiratory viral infections. The successful completion of this application will shed light on the molecular basis underlying the age-associated defects in host response to viral infection and could open the door for novel therapeutics for severe acute diseases and/or chronic lung sequelae after viral infection in aged individuals.


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: 2026 ( Subtotal = $584,156 )
2026	2026	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	001	8	4/21/2026	NON-COMPETING CONTINUATION	$584,156
2026	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	000	6	1/22/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $584,156

Issue Date FY: 2025 ( Subtotal = $614,905 )
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	001	7	6/12/2025	COMPETING CONTINUATION	$614,905
2025	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	000	6	6/4/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $614,905

Issue Date FY: 2024 ( Subtotal = $451,719 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	000	6	5/2/2024	NON-COMPETING CONTINUATION	$451,719
														Subtotal = $451,719

Issue Date FY: 2023 ( Subtotal = $451,719 )
2023	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	000	5	4/21/2023	NON-COMPETING CONTINUATION	$451,719
														Subtotal = $451,719

Issue Date FY: 2022 ( Subtotal = $463,182 )
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	004	4	6/23/2022	NON-COMPETING CONTINUATION	$463,182
2022	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	001	3	4/28/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$270,729
2022	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	2	4/28/2022	NON-COMPETING CONTINUATION	-$270,729
2022	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	003	3	5/26/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$95,364
2022	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	002	2	5/26/2022	NON-COMPETING CONTINUATION	-$95,364
														Subtotal = $463,182

Issue Date FY: 2021 ( Subtotal = $456,012 )
2021	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	2	6/9/2021	NON-COMPETING CONTINUATION	$456,012
														Subtotal = $456,012

Issue Date FY: 2020 ( Subtotal = $456,012 )
2020	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	1	8/11/2020	NEW	$456,012
														Subtotal = $456,012

Grand Total All Awards = $3,477,705

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Elucidating the roles of alveolar macrophage inflammation and self renewal during influenza infection

Award Number: R01AG069264

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2020

PERIOD OF PERFORMANCE END DATE: 04/30/2030

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