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Contaminant Metal Content in Wildfire Smoke and Neuroinflammation

Award Number: R01ES026673
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: 08/01/2016
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Contaminant Metal Content in Wildfire Smoke and Neuroinflammation - SUMMARY Wildland fire disasters raged throughout the western US in recent years, continuing a trend for increasing frequency and severity of such events driven by climate change. Smoke arising from these events covered much of the continent, exposing over 100 million people. Wildland fires in the New Mexico region can cross over regions of legacy mining contamination or nuclear development. Evidence from past fires in Los Alamos, for instance, revealed significant elevations of arsenic, nickel, and cadmium in the urine from first responders. We have further identified that wood obtained near abandoned uranium mine sites that have elevated uranium, chromium, nickel and vanadium. Our recent studies with naturally-occurring wildland fire smoke (WFS) exposures from the California October 2020 wildfires demonstrate clear neuroinflammatory outcomes in otherwise healthy mice. Interestingly, however, after 20 days of exposure, cerebrovascular endothelial cells exhibited an evolving phenotype, with signs of reduced inflammation, signifying an adaptation to the relatively acute circulating inflammatory stimulus. There is a significant gap in knowledge regarding how environmental stressors like WFS promote cerebrovascular inflammation, and even less appreciation for mechanisms governing neuroinflammatory resolution. In the present renewal proposal, we will take what we have learned from extensive field work on uranium mine sites in Laguna Pueblo and Navajo Nation, and return to more precise, laboratory-based exposure systems to address pulmonary and neuroinflammatory risks of wood smoke from metals-contaminated biomass obtained from these regions. Thus, in Aim 1, we will determine the toxic influence of metals in biomass combustion inhalation. We hypothesize that wood obtained near abandoned uranium mine sites, enriched with several metal contaminants, has a greater potency than similar biomass fuels from non-impacted sites. In the 2nd Aim we will elucidate the role of endothelial adhesion molecules in driving neuroinflammatory consequences of wood smoke inhalation. We hypothesize that neuroinflammatory outcomes of woodsmoke are dependent on cerebrovascular expression of adhesion molecules (e.g., ICAM-1, VCAM-1), induced by circulating factors following inhalation exposure. Lastly in Aim 3 we propose to delineate and accelerate the resolution of neuroinflammation after WFS exposures. We hypothesize that neuroinflammatory resolution following woodsmoke exposure, from the standpoint of activated microglia, is actually dependent on the effective recruitment of peripheral immune cells through the neurovascular unit. We will thus ascertain mechanisms underlying the progression of neurovascular tolerance to wood smoke inhalation, thereby identifying potential molecular foundations of vulnerability to long-term consequences of repeated exposure. Furthermore, we will assess the value of pro-resolving lipid mediators in accelerating the resolution, as a potential dietary or therapeutic strategy for acute WFS exposure.


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 = $590,673 )
2026	2026	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Environmental Health	000	9	12/30/2025	NON-COMPETING CONTINUATION	$590,673
														Subtotal = $590,673

Issue Date FY: 2025 ( Subtotal = $590,769 )
2025	2025	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Environmental Health	000	8	2/17/2025	NON-COMPETING CONTINUATION	$590,769
														Subtotal = $590,769

Issue Date FY: 2024 ( Subtotal = $592,021 )
2024	2024	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Environmental Health	000	7	1/16/2024	NON-COMPETING CONTINUATION	$592,021
														Subtotal = $592,021

Issue Date FY: 2023 ( Subtotal = $606,397 )
2023	2023	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Environmental Health	001	6	4/10/2023	COMPETING CONTINUATION	$606,398
2023	2020	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Environmental Health	000	5	3/18/2023	NON-COMPETING CONTINUATION	-$1
														Subtotal = $606,397

Issue Date FY: 2020 ( Subtotal = $470,664 )
2020	2020	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Environmental Health	000	5	9/8/2020	NON-COMPETING CONTINUATION	$470,664
														Subtotal = $470,664

Issue Date FY: 2019 ( Subtotal = $486,483 )
2019	2019	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Environmental Health	000	4	7/19/2019	NON-COMPETING CONTINUATION	$486,483
														Subtotal = $486,483

Issue Date FY: 2018 ( Subtotal = $481,610 )
2018	2018	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Environmental Health	000	3	7/19/2018	NON-COMPETING CONTINUATION	$481,610
														Subtotal = $481,610

Issue Date FY: 2017 ( Subtotal = $494,241 )
2017	2017	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Environmental Health	000	2	7/24/2017	NON-COMPETING CONTINUATION	$494,241
														Subtotal = $494,241

Issue Date FY: 2016 ( Subtotal = $521,024 )
2016	2016	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Environmental Health	000	1	7/22/2016	NEW	$521,024
														Subtotal = $521,024

Grand Total All Awards = $4,833,882

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Contaminant Metal Content in Wildfire Smoke and Neuroinflammation

Award Number: R01ES026673

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: 08/01/2016

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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