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Extracellular vesicles in Environmental Epidemiology Studies of Aging

Award Number: R35ES031688
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/06/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2030

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Extracellular vesicles in Environmental Epidemiology Studies of Aging - SUMMARY Through this RIVER proposal, I seek support to characterize and understand early biological responses that anticipate age-related disease, which typically develops from exposures that occurred much earlier in life. My primary focus will be on the effects of air pollution on accelerated brain aging, a major interest of my lab. Ambient air particulate pollution has been shown to hasten cognitive aging by as much as 5 years. Because of the strong age dependence of dementia, merely delaying its onset could have a dramatic impact. For effectively preventing such effects, we need to develop biomarkers that reflect not only adverse exposures, but also preclinical effects on cognitive function and brain health deterioration. That is, we need to find easy-to-use tools to detect the impact of air pollution and the beginnings of cognitive decline before they manifest fully. To address this urgent clinical and public health need, I propose a series of coordinated human and in vitro studies of an underappreciated cellular communication system enabled by extracellular vesicles (EVs). EVs are nano-sized (0.05–1 μm) membrane-bound vesicles released by human cells into the bloodstream that contain cargo, such as microRNAs, that can be integrated into recipient cells and modify their biology. We have built capacity to isolate circulating EVs based on their source cell type (SCT) using surface markers that EVs derive from the cells that released them. These new methods will enable my lab to identify signals from the precise cell types and organs affected by the exposures. We will apply these new methods to large cohort studies with existing blood samples and clinical data collected longitudinally at multiple time points over decades of follow-up to identify specific communication routes mediating the adverse effects of air pollution on the brain. Based on preliminary evidence and pilot data, my hypothesis is that circulating EVs released by the lung in response to air pollution carry signals, including microRNAs, that can that reach the brain and accelerate brain aging. In parallel, we will conduct in vitro studies investigating how EVs released by the lung in response to air pollution affect brain function using human bronchial epithelial cell cultures and cultured 3D brain organoids—a novel model that can be used to study the neurodegenerative processes underlying age- related brain health deterioration. Further, I will apply current data science techniques to identify patterns activated by environmental exposures and predictive of future health outcomes. I am confident that I can successfully lead this program. Over the last 10 years, I served as (M)PI on 16 NIH- funded awards. My work has produced >450 publications, and I was recently recognized as one of the highest cited, most influential investigators of the past decade. I have demonstrated a broad vision and made seminal contributions to the understanding of molecular mechanisms, including EVs, that are part of homeostatic alterations caused by environmental exposures. The flexible and sustained RIVER support will help continue a highly successful record of innovation and leadership in environmental health sciences.


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 = $815,932 )
2026	2026	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Environmental Health	000	5	7/3/2026	NON-COMPETING CONTINUATION	$815,932
														Subtotal = $815,932

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Environmental Health	001	4	9/18/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2023	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Environmental Health	000	3	2/20/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $826,656 )
2024	2024	HARVARD COLLEGE PRESIDENT & FELLOWS OF	677 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Environmental Health	001	4	8/5/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$826,656
2024	2023	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Environmental Health	000	3	8/5/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $826,656

Issue Date FY: 2023 ( Subtotal = $996,221 )
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Environmental Health	000	3	6/8/2023	NON-COMPETING CONTINUATION	$934,140
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Environmental Health	001	3	6/9/2023	SUPPLEMENT FOR EXPANSION	$62,081
														Subtotal = $996,221

Issue Date FY: 2022 ( Subtotal = $1,027,227 )
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	Environmental Health	001	2	7/4/2022	SUPPLEMENT FOR EXPANSION	$62,081
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	Environmental Health	000	2	6/27/2022	NON-COMPETING CONTINUATION	$965,146
														Subtotal = $1,027,227

Issue Date FY: 2021 ( Subtotal = $958,370 )
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	Environmental Health	000	1	7/5/2021	NEW	$958,370
														Subtotal = $958,370

Grand Total All Awards = $4,624,406

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Extracellular vesicles in Environmental Epidemiology Studies of Aging

Award Number: R35ES031688

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/06/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2030

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