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Environmental Cadmium and COPD

Award Number: R01ES029981
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: 09/21/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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Environmental Cadmium and COPD - The lung is a major portal for respirable environmental toxicants including heavy metals such as cadmium (Cd), which is recognized to cause chronic obstructive pulmonary disease (COPD). COPD is the third largest cause of mortality in the US. Airway remodeling with loss of the lumen of small airways and airflow obstruction precede airspace enlargement and emphysema. Airway remodeling is associated with a profusion of airway fibroblasts and an increase in extracellular matrix proteins. Vimentin is an intracellular type 3 filament that can trigger peribronchial fibrosis. The prevalence of COPD is twice as high in a zip code where a Superfund site is located in Birmingham, Alabama when compared to a control zip code with similar demographics and smoking prevalence. We postulate that chronic low dose cadmium (Cd) exposure induces alterations in vimentin-mitochondrial dynamics that results in mitochondrial dysfunction and aberrant activation of peribronchiolar fibroblasts leading to bronchiolar luminal narrowing and subsequent COPD. We will examine this hypothesis in the following specific aims: (1) Determine whether exposure to Cd in a cohort of smokers and never-smokers from a Birmingham community predicts susceptibility to airway remodeling and COPD. (2) Determine the mechanisms by which Cd mediates alterations in vimentin-mitochondrial dynamics to regulate fibroblast activation. (3) Determine whether low dose Cd, or pSer39Vim induced airway remodeling and airspace enlargement in a mouse model of COPD is associated with fibroblast invasion, ECM deposition and apoptosis resistance. These studies will directly address a significant gap in our understanding of how cadmium contributes to the pathogenesis of COPD and the role of vimentin filaments in mitochondrial homeostasis. Early biomarkers of COPD in exhaled breath condensate may help us recognize disease susceptibility. Importantly, these studies may provide novel therapeutic strategies in patients with COPD.


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: 2025 ( Subtotal = $0 )
2025	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Environmental Health	000	5	1/3/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $486,082 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Environmental Health	000	5	6/23/2022	NON-COMPETING CONTINUATION	$486,082
														Subtotal = $486,082

Issue Date FY: 2021 ( Subtotal = $508,131 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Environmental Health	000	4	6/15/2021	NON-COMPETING CONTINUATION	$508,131
														Subtotal = $508,131

Issue Date FY: 2020 ( Subtotal = $508,131 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Environmental Health	000	3	6/29/2020	NON-COMPETING CONTINUATION	$508,131
														Subtotal = $508,131

Issue Date FY: 2019 ( Subtotal = $508,131 )
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Environmental Health	001	2	6/24/2019	NON-COMPETING CONTINUATION	$508,131
2019	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Environmental Health	000	1	12/14/2018	NEW	$0
														Subtotal = $508,131

Issue Date FY: 2018 ( Subtotal = $486,083 )
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Environmental Health	000	1	9/20/2018	NEW	$486,083
														Subtotal = $486,083

Grand Total All Awards = $2,496,558

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Environmental Cadmium and COPD

Award Number: R01ES029981

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: 09/21/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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