PROJECT SUMMARY AND ABSTRACT
From the 1940s-1980s, corporate uranium (U) mines were established in the Southwestern United States,
many on Native American lands. Due to improper reclamation and poor remediation, surrounding residential
homes are subject to residual mixed-metals exposure including arsenic (As), vanadium (V), uranium (U), and
nickel (Ni) via ingestion and inhalation. Inhaled metal-based derived particulate matter (PM) has been
associated with an increase in circulating serum inflammatory potential and subsequent vascular and
neurovascular disease. The full scope of systemic health effects following inhaled mine-site derived PM has
yet to be elucidated and the role of circulating factors, such as small extracellular vesicles (sEVs) in driving
inflammatory impacts is underexplored.
In preliminary studies, we have observed that mine-site PM is more acutely toxic to pulmonary and
vascular systems than regional ‘background’ PM. Furthermore, similar studies of inhaled particulates and
gases demonstrate endothelial dysfunction that can drive vascular dysfunction and inflammatory outcomes.
Therefore, my specific aims will serve three primary objectives 1) mechanistically delineate lung-sEV
biogenesis following PM exposure 2) mechanistically evaluate sEV endocytosis following PM exposures and 3)
assess associations between type of mining dust exposure (U-mining vs. non-U mining) and sEV vascular
biomarkers in an established human cohort of former miners (the MiDUS cohort, Mining Dust in the United
States). This proposal serves as an innovative, five-year research project to understand the mechanistic role of
sEVs in driving toxic responses following PM exposure. We shall leverage the outstanding facilities and
resources at the University of New Mexico – Health Sciences Center, including the Autophagy, Inflammation
and Metabolism (AIM) Center (P20GM121176), the University of New Mexico Center for Metals in Biology and
Medicine (P20GM130422), the UNM Mobile Epidemiology Laboratory (MEL) and our long-standing
collaborations with community partners, including the Miners’ Colfax Medical Center Mobile Outreach.
With global extraction of metal ores surging due to increased demand for batteries, computer chips and
energy, environmental mixed-metals exposure has become an issue of concern in both an occupational and
environmental context. Data from these studies will ultimately lead to essential information pertinent to metal-
exposed populations, as well as governing agencies involved in air-quality regulations.
