# Extracellular vesicles in Environmental Epidemiology Studies of Aging

> **NIH NIH R35** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $958,370

## Abstract

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...

## Key facts

- **NIH application ID:** 10198224
- **Project number:** 1R35ES031688-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Andrea Baccarelli
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $958,370
- **Award type:** 1
- **Project period:** 2021-07-05 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198224

## Citation

> US National Institutes of Health, RePORTER application 10198224, Extracellular vesicles in Environmental Epidemiology Studies of Aging (1R35ES031688-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10198224. Licensed CC0.

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