Laurie G. Hudson, PhD
Debra MacKenzie, PhD
Esther Erdei, PhD
David Begay, PhD
Erica Dashner-Titus, PhD
Partnering with Native American communities, the UNM Metals Exposure and Toxicity Assessment on Tribal Lands in the Southwest (UNM METALS) team has obtained evidence for community level exposures and health risks associated with more than 1100 abandoned uranium mine (AUM) waste sites on their tribal lands. Biomonitoring results confirm that community members are exposed to uranium and other metals beyond national norms, leading to community concerns about potential impact on health.
This project addresses Native American community concerns about health effects associated with exposure to uranium and co-occurring metals found at legacy uranium mining waste sites. Our studies will investigate the biologic consequences of mixed metals exposure in impacted communities. We will use biomonitoring to assess current exposures to mixed metals and metalloids. Based on preliminary findings and published work, we will test the hypothesis that exposure to the unique mixtures of environmental metals associated with abandoned uranium mines promotes oxidative stress and inflammatory responses, processes known to promote immune dysregulation and development of numerous chronic diseases. Complementary studies in experimental models are designed to identify mechanisms of toxicity that can be targeted for future population-based interventions.
This project is responsive to community concerns and the outcomes are expected to 1) provide insights into biological consequences of understudied toxic metals identified in environmental samples and elevated in biospecimens from the community, 2) expand mechanistic knowledge of the impact of specific metals and metal mixtures as well as the basis for metal interactions in human immune cells, and 3) experimentally test the potential of mechanism-based interventions to confer protection from environmental metal exposures. Our ultimate goal is to leverage mechanistic science toward development of interventional clinical trials to mitigate the health risks of ongoing metals exposures.
Adrian Brearley, PhD
Eliane El Hayek, PhD
Jose Cerrato, PhD
Joseph Galewsky, PhD
Many Native American communities in the Southwest US live in close proximity to numerous abandoned uranium mines (AUMs) that were active in the 1950s through 1980s. These communities are revitalizing agricultural activities on lands adjacent to abandoned mine sites that may have been contaminated by windblown dust during active and post mining activities. Two significant concerns of these tribal communities are: i) potential exposure to windblown, respirable (PM2.5), metals-bearing particulates; and ii) whether agricultural crops grown on tribal lands adjacent to AUMs could represent a potential exposure pathway that is detrimental to human health. Legacy uranium (U) mine sites in semi-arid regions are subject to strong aeolian (wind-related) processes, which influence the dispersion of U-bearing mineral dust, causing concern for human exposures to toxic dust that has potential negative health impacts. Understanding the bioavailability and bioaccessibility of U and co-occurring toxic metals in PM2.5, especially nanoparticulates in arising fugitive mineral dusts from legacy mine sites is important to identify health risks to affected communities.
The ESE PM project focus on the environmental risks of nanoparticle exposure stems from our preliminary results which show that previously unrecognized U-bearing nanoparticles are present in a range of different natural materials related to AUMs. Our research strategy will develop an understanding of: a) the origin, abundance, and physicochemical characteristics of nanoparticulate forms of U and co-occurring metals in mine wastes, soils, and windblown dust on tribal lands; b) their transport and redistribution due to windblown suspension presenting inhalation exposures, as well as contamination of agricultural lands and crops; 3) the relationship between the metals content of agricultural soil and uptake into agricultural crops that are a potential ingestion exposure pathway; and 4) the uptake mechanisms of these toxic metals into agricultural crops via root and foliar systems.
This project will provide data to address the concerns of tribal communities regarding potential exposure pathways from suspended PM (particulate matter) arising from legacy mine sites. Our findings will test the hypothesis that windblown transport of PM2.5 originating from AUMs represents a unique exposure-risk scenario to humans through inhalation and ingestion, based on the complex physicochemical characteristics of metal mixtures contained in the PM. Our results will establish the extent to which the complex metal mixtures in airborne PM released from AUM sites pose a health hazard and will more accurately address risk reduction strategies for these vulnerable populations who live in proximity to AUMs. This information will help to mitigate human exposures to metals mixtures resulting from the inhalation of windblown dust and the consumption of crops on agricultural lands that may have been contaminated by fugitive dust from mine sites both during their active phase of mining and in the present day.
Eliseo F. Castillo, PhD, Division of Gastroenterology & Hepatology, Department of Internal Medicine, UNM HSC
Julie G. In, PhD, Division of Gastroenterology & Hepatology, Department of Internal Medicine, UNM HSC
Abandoned uranium mines (AUMs) are concentrated in the Southwestern United States, with many on tribal lands. The Native American communities surrounding AUMs have voiced their concerns that uranium (U) and arsenic (As) exposures arising from AUM sites have increased the prevalence of chronic and systemic diseases, including immune dysfunction and cancer. Our previous research on environmental metal exposure focused on cardiovascular and pulmonary effects; however, realizing that inhalation intake strongly contributes to gut exposure through contaminated mucus ingestion, we are interested in gastrointestinal (GI) health. Additionally, the GI tract is also readily exposed to environmental metals through contaminated food and water sources. Thus, the ultimate goal of these studies is to address community concerns regarding exposure to mixed metals from AUM waste and other hard metal mines leading to potential immunologic changes and diseases originating from the GI tract.
The researchers for BP Gut are experts in gut biology and immunology and intend to determine how these environmental metals affect three aspects of the gut. There is a tripartite interaction involving the microbiota (microorganisms living in our gut), the immune system, and the intestinal epithelium which maintains the balance between intestinal homeostasis and inflammation. Dysfunction in one of these components can have profound effects on the other two systems as well as systemic health. Therefore, we will utilize animal models and human intestinal organoids to decipher how gut exposures to environmental pollutants disrupts GI health.
Chronic exposure to metal mixtures from AUM wastes have been linked to increased risk for diseases including hypertension, diabetes, autoimmunity, and kidney disease in adult studies. This disproportionally affects Native American communities in the Southwestern United States. Our work will provide critical mechanistic insights into the potential immunotoxicity of U and As in GI physiology and disease pathophysiology.
Alicia Bolt, PhD
Sarah Blossom, PhD
Katherine Zychowski, PhD
Inhalation of mine site dust is a potential route of human exposure to metal mixtures that poses a significant health concern for tribal communities living near abandoned uranium and hard rock mine sites in the four-corners region of the Southwestern United States. Persistent lung inflammation is associated with multiple immune-mediated inflammatory disorders including autoimmune disease. However, the contribution and extent of inhaled mine site-derived metal particles to immune dysregulation and the development of autoimmunity is unknown.
One hypothesis of this project is that mine site dust containing metal particles drives lung and systemic immune dysregulation and autoimmunity through the hyperactivation of neutrophils. Our initial studies, using autoimmune prone mice, suggest that inhalation exposure to mine site dust leads to the hyperactivation of neutrophils resulting in the formation of neutrophil extracellular traps (NETosis), which is an important driver of pulmonary inflammation. Using advanced cell and mouse models, as well as health studies in exposed populations, our research team is investigating the role of activated neutrophils and NETosis in the development of lung and systemic immune dysregulation following mine site dust exposure.
Information gained from this project will provide novel insight into the potential risks associated with exposure to airborne metals and their role in metal-mediated immune modulation and disease.
Anjali Mulchandani, PhD
Jennifer Rudgers, PhD
Eliane El Hayek, PhD
Jose Cerrato, PhD
Previous studies of the UNM METALS Superfund Research Center report the co-occurrence of mixtures of uranium (U), arsenic (As), and vanadium (V) in waters and soils in sites affected by mining legacies in our partner communities in the Pueblo of Laguna and Navajo Nation. The burden of mining activities has affected various Superfund sites in the U.S., causing multigenerational metal exposures in our partner communities. Various sites affected by mining legacy in the US have not been adequately reclaimed or remediated.
The proposed research will contribute novel mechanistic insights that will enable the development of bioreactors catalyzed by plant-fungal symbiosis coupled with absorption and precipitation using natural minerals for sustainable bioremediation of metal mixtures. Calcium-minerals are naturally abundant in our partner communities, and we intend to further evaluate how these minerals react with phosphate to immobilize uranium and arsenic. We will also use fungi isolates obtained from sites located in our partner communities to identify relevant temperature stress gradients, water chemistry, and other environmental conditions in the Southwestern US influencing the uptake of metal mixtures by plant-fungal symbiosis. We will engineer bioreactors to identify environmental conditions that best promote metal uptake, mineral adsorption, and chemical precipitation by plant-associated fungi, informing predictions on bioremediation potential induced by future climate change.
This project will develop novel technologies for bioremediation by harnessing plant-fungal symbioses to immobilize metal mixtures through mineral absorption and precipitation. The co-occurrence of mixtures of uranium (U), arsenic (As), and vanadium (V) has been reported in waters and soils in natural geologic deposits and Superfund sites affected by mining legacies. However, few studies examine the reactivity of metal mixtures in environmentally relevant conditions. The integration of physicochemical and biological processes provides invaluable opportunities to gain new insights essential to risk assessment and to the advancement of novel bioremediation technologies.
