2012 Progress Report: Great Lakes Air Center for Integrative Environmental Research (GLACIER)

EPA Grant Number: R834797
Center: Great Lakes Air Center for Integrative Environmental Research
Center Director: Harkema, Jack
Title: Great Lakes Air Center for Integrative Environmental Research (GLACIER)
Investigators:
Current Investigators: Brooks, Robert P. , Araujo, Jesus , Kaplan, Marianna J. , Oral, Elif
Institution: Michigan State University , The Ohio State University - Main Campus , University of California - Los Angeles , University of Michigan - Ann Arbor
EPA Project Officer: Ilacqua, Vito
Project Period: January 1, 2011 through December 31, 2015 (Extended to December 31, 2016)
Project Period Covered by this Report: January 1, 2012 through December 31,2012
Project Amount: $7,999,875
RFA: Clean Air Research Centers (2009) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

Exposure Characterization Core (University of Michigan)

PI: J. Timothy Dvonch, Ph.D.

The GLACIER Air Pollution Center includes three projects to assess the impacts of air pollution exposure at field study locations with specific types of air pollution emission source impacts. Our Center’s overall hypothesis is that primary air pollutants, fine particulate matter (PM2.5) and ozone (O3), are (1) capable of causing important adverse health effects that are (2) dependent on the local combinations of air pollutants, (3) a person’s pre-existing health condition, and (4) the interactive adverse effects of exposure to both PM2.5 and O3. As part of GLACIER, our Exposure Characterization Core (ECC) coordinates with and supports GLACIER Projects 1-3 to provide measurements of air pollutant exposure. Our previous work in human population studies, as well as human and animal studies of exposure to concentrated ambient particles (CAP) and ozone have demonstrated the critical importance of complete exposure characterization. Several of these studies have identified adverse health effects related to metabolic syndrome such as development of high blood pressure due to specific components of air pollution, as well as specific sources of air pollution. Because ambient PM is currently regulated on a mass basis, assuming all particles equally impact health, it is clear that in order to determine the most effective way in which to regulate PM and ensure that reductions in PM do in fact improve human health, additional studies are required. The proposed ECC is designed to investigate the components and sources of air pollution prominent across the Great Lakes region that are responsible for adverse health effects. The ECC is highly innovative in design by virtue of the use of mobile ambient particle concentrators coupled with mobile toxicological laboratories to evaluate the acute health effects of air pollution dominated by different chemical components and sources. These mobile labs will be stationed in three communities in Michigan (Detroit, Dearborn, and Dexter) for short-term exposure studies conducted in Projects 1 and 2, as well as two locations in Columbus, OH, for long-term exposure studies in Project 3. The ECC will specifically utilize these five exposure sites in Michigan and Ohio primarily impacted by (1) near-roadway motor vehicle emissions (two sites), (2) industrial point sources (one site), and (3) regionally transported air pollution (no local emission sources, two sites). The primary objectives of the ECC are to: characterize the chemical components of air pollution exposure, identify the sources of air pollution exposure, and assess the air pollution components and sources responsible for the adverse cardiometabolic responses observed for each of Projects 1-3.

Biostatistics and Data Management Core (University of Michigan)

PIs: Bhramar Mukherjee, Ph.D., and Cathie Spino, Sc.D.

The overarching thesis of the EPA Great Lakes Air Center for Integrated Environmental Research (GLACIER) is that the primary air pollutants, fine particulate matter (PM2.5) and ozone (O3), cause cardiometabolic health effects that are dependent on 1) the local multipollutant atmospheric milieu, 2) the individual’s pre-existing cardiovascular and metabolic condition, and 3) the interactive toxicity of PM2.5 and O3 coexposure. The objectives of the GLACIER Biostatistics and Data Management Core (BDMC) are to provide guidance for the statistical design and analysis of studies and data management services that allow for the integration of the data into a single platform that facilitates timely analysis for GLACIER investigators and projects. In the modern era of environmental sciences research, research investigators are generating a vast amount of data on multiple pollutants, health outcomes with the goal of studying the health effects caused by an ensemble of pollutants. Although our understanding of the mechanisms in which multipollutant mixtures cause/affect/mediate chronic diseases remains in its infancy, a major goal of this core is to equip the investigators of GLACIER to face the challenges in exploring the intricacies of statistical modeling for mixtures of pollutants. The Core, consisting of biostatisticians, experienced with working on problems relevant to environmental health sciences, will equip the investigator with state of the art statistical modeling techniques to understand the generated data.

In addition, essential attention to data collection and management activities prior to and during the conduct of studies in a platform that allows collaborative interchange between the scientists at the source of the data and statisticians at the analytic end of the data provides the ability to analyze complex and rich data more fully and efficiently at the close of each study.

Progress Summary:

Exposure Characterization Core (University of Michigan)

PI: J. Timothy Dvonch, Ph.D.

There have been no changes in ECC core investigators. To date in Year 2 of the ECC core, we have successfully completed the human exposures for Project 1 at our rural Dexter, MI site for all subjects (including 2 exposures per subject, coarse CAP and filtered air), and are now working to complete laboratory analysis and data analyses for PM mass and associated components. We are also active now in the transition phase of Project 1, where we are preparing all logistical aspects to move our mobile exposure facility to the urban/industrial Dearborn site, which is expected to take place in September 2012.

We have also completed the first phase of acute animal exposures for Project 2, which took place at the Dearborn site, the field component of which was completed in late August of 2011. Exposure characterization for these exposure studies included operation of the SEAS aerosol slurry sampler mobile laboratory, as well as the EPA collaborative components of GLACIER Year 1: the EPA Chemvol Tox mobile lab and Tisch samplers for organic speciation. Laboratory analysis and data analyses for PM mass and associated components for these exposure studies are ongoing. Last, chronic animal exposures and associated exposure characterization as part of Project 3 began during the latter half of 2011 at the Columbus sites. Data and sample collection and analysis are ongoing as part of these efforts.

Biostatistics and Data Management Core (University of Michigan)

PIs: Bhramar Mukherjee, Ph.D., and Cathie Spino, Sc.D.

The Biostatistics and Data Management Core has collaborated with investigators from Project 2 to QC and analyze the first experiment investigating acute CAP and ozone exposures in rodent models of cardiometabolic syndrome. Analyses resulted in an abstract and presentation at the Society of Toxicology 51st Annual Meeting, March 11–15, 2012, in San Francisco, CA. The Core also re-assessed the sample size considerations for the first experiment of Project 1, supporting a reduction in the sample size. Finally, Drs. Mukherjee and Spino participated in the CLARC Biostatistics Workshop in Boston in June 2012.

In addition to statistical activities, the Core has enhanced and maintained the public access website (http://greatlakesairresearchcenter.org/ Exit ), collaborating with Dr. Jack Harkema and other project investigators. It provides information about GLACIER, its Projects and Cores, a directory of key personnel for each project, information on the Mobile Labs, and links to Clean Air Centers and other EPA links. There is a link to future publications that will arise from this research. Effort began this reporting period to build the GLACIER intranet, with user accounts created. In addition, standard formatting of study information including study design, codebooks, descriptive statistics (both tabular and graphical) and analysis datasets were created and implemented for the first GLACIER studies from Project 2. Discussions with Project 1 and the Exposure Core were held to provide input into data structures and prepare for expedient analysis of Project 1 and incorporation of Exposure Core data into analyses of cardiometabolic parameters.

Design consultation on each project is being provided by Dr. Bhramar Mukherjee (Project 1), Dr. Brisa Sanchez (Project 2) and Dr Lu Wang (Project 3).

Future Activities:

Exposure Characterization Core (University of Michigan)

PI: J. Timothy Dvonch, Ph.D.

Exposure characterization in support of human exposures for Project 1 will transition from the rural Dexter site to the urban/industrial Dearborn site in September 2012. These human exposures at the Dearborn site will continue through Year 3 of the project. The next phase of exposure characterization activities in support of animal exposures for Project 2 are scheduled to be conducted at the rural Dexter site in late 2012/early 2013, with associated lab activities continuing through Year 3 of the project. Chronic animal exposures and associated exposure characterization as part of Project 3 are ongoing at the Columbus sites, and will continue through 2012 and into Year 3 of the project. Data and sample collection and analysis are ongoing as part of these efforts and will continue as scheduled through Year 1 and into Year 2 of the study. Exposure characterization in support of Project 2 at the urban Dearborn site will also continue according to schedule through summer of Year 1, and again during summer of Year 2. Years 1 and 2 of ECC Core activities are heavily focused on carrying out the logistics of site preparation and installation for field-based exposure studies. In the current Year 2 and more so into Year 3, the large lab-based analytical effort currently underway with specific focus on chemical characterization of collected exposure samples and associated data processing and QA will develop into drafting of additional conference presentations and associated publications.

Biostatistics and Data Management Core (University of Michigan)

PIs: Bhramar Mukherjee, Ph.D., and Cathie Spino, Sc.D.

In the next reporting period, additional analyses will be run to finalize interpretation of the first experiments for Project 2, as well as completion of analyses for the second and third experiments for Project 2. Analyses will commence for the randomized controlled experiment for Project 1, beginning with QC efforts and descriptive statistics. In addition, maintenance of the GLACIER public website and enhancement and further development of the GLACIER intranet will take continue. Project 3 data and Exposure Core data will be transferred to the GLACIER intranet. Research methods development on high-resolution temporal data being generated in Project 1 using multi-scale models will remain a primary focus in Year 2.


Journal Articles: 71 Displayed | Download in RIS Format

Other center views: All 147 publications 71 publications in selected types All 71 journal articles
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Journal Article Balasubramanian P, Sirivelu MP, Weiss KA, Wagner JG, Harkema JR, Morishita M, Mohankumar PS, Mohankumar SM. Differential effects of inhalation exposure to PM 2.5 on hypothalamic monoamines and corticotrophin releasing hormone in lean and obese rats. NeuroToxicology 2013;36:106-111. R834797 (2013)
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  • Journal Article Blazek A, Rutsky J, Osei K, Maiseyeu A, Rajagopalan S. Exercise-mediated changes in high-density lipoprotein: impact on form and function. American Heart Journal 2013;166(3):392-400. R834797 (2013)
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  • Journal Article Brandenberger C, Li N, Jackson-Humbles DN, Rockwell CE, Wagner JG, Harkema JR. Enhanced allergic airway disease in old mice is associated with a Th17 response. Clinical & Experimental Allergy 2014;44(10):1282-1292. R834797 (2014)
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  • Journal Article Brook RD, Rajagopalan S, Pope III CA, Brook JR, Bhatnagar A, Diez-Roux AV, Holguin F, Hong Y, Luepker RV, Mittleman MA, Peters A, Siscovick D, Smith SC, Whitsel L, Kaufman JD. Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation 2010;121(21):2331-2378. R834797 (2016)
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  • Journal Article Brook RD, Rajagopalan S. Can what you breathe trigger a stroke within hours? Comment on "ambient air pollution and the risk of acute ischemic stroke". Archives of Internal Medicine 2012;172(3):235-236. R834797 (2014)
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  • Journal Article Brook RD, Bard RL, Kaplan MJ, Yalavarthi S, Morishita M, Dvonch JT, Wang L, Yang H-Y, Spino C, Mukherjee B, Oral EA, Sun Q, Brook JR, Harkema J, Rajagopalan S. The effect of acute exposure to coarse particulate matter air pollution in a rural location on circulating endothelial progenitor cells: results from a randomized controlled study. Inhalation Toxicology 2013;25(10):587-592. R834797 (2013)
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  • Journal Article Brook RD, Xu X, Bard RL, Dvonch JT, Morishita M, Kaciroti N, Sun Q, Harkema J, Rajagopalan S. Reduced metabolic insulin sensitivity following sub-acute exposures to low levels of ambient fine particulate matter air pollution. The Science of the Total Environment 2013;448:66-71. R834797 (2012)
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  • Journal Article Brook RD, Bard RL, Morishita M, Dvonch JT, Wang L, Yang HY, Spino C, Mukherjee B, Kaplan MJ, Yalavarthi S, Oral EA, Ajluni N, Sun Q, Brook JR, Harkema J, Rajagopalan S. Hemodynamic, autonomic, and vascular effects of exposure to coarse particulate matter air pollution from a rural location. Environmental Health Perspectives 2014;122(6):624-630. R834797 (2013)
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  • Journal Article Byrd JB, Morishita M, Bard RL, Das R, Wang L, Sun Z, Spino C, Harkema J, Dvonch JT, Rajagopalan S, Brook RD. Acute increase in blood pressure during inhalation of coarse particulate matter air pollution from an urban location. Journal of the American Society of Hypertension 2016;10(2):133-139. R834797 (2016)
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  • Journal Article Carey SA, Ballinger CA, Plopper CG, McDonald RJ, Bartolucci AA, Postlethwait EM, Harkema JR. Persistent rhinitis and epithelial remodeling induced by cyclic ozone exposure in the nasal airways of infant monkeys. American Journal of Physiology:Lung Cellular and Molecular Physiology 2011;300(2):L242-L254. R834797 (2014)
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  • Journal Article Deiuliis JA, Kampfrath T, Zhong J, Oghumu S, Maiseyeu A, Chen LC, Sun Q, Satoskar AR, Rajagopalan S. Pulmonary T cell activation in response to chronic particulate air pollution. American Journal of Physiology:Lung Cellular and Molecular Physiology 2012;302(4):L399-L409. R834797 (2014)
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  • Journal Article Fonken LK, Xu X, Weil ZM, Chen G, Sun Q, Rajagopalan S, Nelson RJ. Air pollution impairs cognition, provokes depressive-like behaviors and alters hippocampal cytokine expression and morphology. Molecular Psychiatry 2011;16(10):987-995. R834797 (2014)
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  • Journal Article Giorgini P, Rubenfire M, Das R, Gracik T, Wang L, Morishita M, Bard RL, Jackson EA, Fitzner CA, Ferri C, Brook RD. Higher fine particulate matter and temperature levels impair exercise capacity in cardiac patients. Heart 2015;101(16):1293-1301. R834797 (2014)
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  • Journal Article Giorgini P, Rubenfire M, Das R, Gracik T, Wang L, Morishita M, Bard RL, Jackson EA, Fitzner CA, Ferri C, Brook RD. Particulate matter air pollution and ambient temperature: opposing effects on blood pressure in high-risk cardiac patients. Journal of Hypertension 2015;33(10):2032-2038. R834797 (2014)
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  • Journal Article Gong Jr. H, Linn WS, Terrell SL, Clark KW, Geller MD, Anderson KR, Cascio WE, Sioutas C. Altered heart-rate variability in asthmatic and healthy volunteers exposed to concentrated ambient coarse particles. Inhalation Toxicology 2004;16(6-7):335-343. R834797 (2016)
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  • Journal Article Huang W, Wang L, Li J, Liu M, Xu H, Liu S, Chen J, Zhang Y, Morishita M, Bard RL, Harkema JR, Rajagopalan S, Brook RD. Short-term blood pressure responses to ambient fine particulate matter exposures at the extremes of global air pollution concentrations. American Journal of Hypertension 2018;31(5):590-599. R834797 (Final)
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  • Journal Article Hubbs AF, Mercer RR, Benkovic SA, Harkema J, Sriram K, Schwegler-Berry D, Goravanahally MP, Nurkiewicz TR, Castranova V, Sargent LM. Nanotoxicology--a pathologist's perspective. Toxicologic Pathology 2011;39(2):301-324. R834797 (2014)
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  • Journal Article Kamal AS, Rohr AC, Mukherjee B, Morishita M, Keeler GJ, Harkema JR, Wagner JG. PM2.5-induced changes in cardiac function of hypertensive rats depend on wind direction and specific sources in Steubenville, Ohio. Inhalation Toxicology 2011;23(7):417-430. R834797 (2014)
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  • Journal Article Liu C, Ying Z, Harkema J, Sun Q, Rajagopalan S. Epidemiological and experimental links between air pollution and type 2 diabetes. Toxicologic Pathology 2013;41(2):361-373. R834797 (2013)
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  • Journal Article Liu C, Xu X, Bai Y, Wang TY, Rao X, Wang A, Sun L, Ying Z, Gushchina L, Maiseyeu A, Morishita M, Sun Q, Harkema JR, Rajagopalan S. Air pollution-mediated susceptibility to inflammation and insulin resistance:influence of CCR2 pathways in mice. Environmental Health Perspectives 2014;122(1):17-26. R834797 (2013)
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  • Journal Article Liu C, Bai Y, Xu X, Sun L, Wang A, Wang TY, Maurya SK, Periasamy M, Morishita M, Harkema J, Ying Z, Sun Q, Rajagopalan S. Exaggerated effects of particulate matter air pollution in genetic type II diabetes mellitus. Particle and Fibre Toxicology 2014;11:27. R834797 (2014)
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  • Journal Article Liu C, Fonken LK, Wang A, Maiseyeu A, Bai Y, Wang T-Y, Maurya S, Ko Y-A, Periasamy M, Dvonch T, Morishita M, Brook RD, Harkema J, Ying Z, Mukherjee B, Sun Q, Nelson RJ, Rajagopalan S. Central IKKβ inhibition prevents air pollution mediated peripheral inflammation and exaggeration of type II diabetes. Particle and Fibre Toxicology 2014;11:53. R834797 (2014)
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  • Journal Article Maiseyeu A, Yang H-Y, Ramanathan G, Yin F, Bard RL, Morishita M, Dvonch JT, Wang L, Spino C, Mukherjee B, Badgeley MA, Barajas-Espinosa A, Sun Q, Harkema J, Rajagopalan S, Araujo JA, Brook RD. No effect of acute exposure to coarse particulate matter air pollution in a rural location on high-density lipoprotein function. Inhalation Toxicology 2014;26(1):23-29. R834797 (2014)
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  • Journal Article Maniar-Hew K, Postlethwait EM, Fanucchi MV, Ballinger CA, Evans MJ, Harkema JR, Carey SA, McDonald RJ, Bartolucci AA, Miller LA. Postnatal episodic ozone results in persistent attenuation of pulmonary and peripheral blood responses to LPS challenge. American Journal of Physiology:Lung Cellular and Molecular Physiology 2011;300(3):L462-L471. R834797 (2014)
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  • Journal Article Mathew AV, Yu J, Guo Y, Byun J, Chen YE, Wang L, Liu M, Bard RL, Morishita M, Huang W, Li J, Harkema JR, Rajagopalan S, Pennathur S, Brook RD. Effect of ambient fine particulate matter air pollution and colder outdoor temperatures on high-density lipoprotein function. The American Journal of Cardiology 2018;122(4):565-570. R834797 (Final)
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  • Journal Article Mendez R, Zheng Z, Fan Z, Rajagopalan S, Sun Q, Zhang K. Exposure to fine airborne particulate matter induces macrophage infiltration, unfolded protein response, and lipid deposition in white adipose tissue. American Journal of Translational Research 2013;5(2):224-234. R834797 (2016)
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  • Journal Article Morishita M, Keeler GJ, Kamal AS, Wagner JG, Harkema JR, Rohr AC. Source identification of ambient PM2.5 for inhalation exposure studies in Steubenville, Ohio using highly time-resolved measurements. Atmospheric Environment 2011;45(40):7688-7697. R834797 (2014)
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  • Journal Article Morishita M, Keeler GJ, Kamal AS, Wagner JG, Harkema JR, Rohr AC. Identification of ambient PM2.5 sources and analysis of pollution episodes in Detroit, Michigan using highly time-resolved measurements. Atmospheric Environment 2011;45(8):1627-1637. R834797 (2014)
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  • Journal Article Morishita M, Bard RL, Kaciroti N, Fitzner CA, Dvonch T, Harkema JR, Rajagopalan S, Brook RD. Exploration of the composition and sources of urban fine particulate matter associated with same-day cardiovascular health effects in Dearborn, Michigan. Journal of Exposure Science & Environmental Epidemiology 2015;25(2):145-152. R834797 (2014)
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  • Journal Article Morishita M, Bard RL, Wang L, Das R, Dvonch JT, Spino C, Mukherjee B, Sun Q, Harkema JR, Rajagopalan S, Brook RD. The characteristics of coarse particulate matter air pollution associated with alterations in blood pressure and heart rate during controlled exposures. Journal of Exposure Science & Environmental Epidemiology 2015;25(2):153-159. R834797 (2014)
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  • Journal Article Munzel T, Sorensen M, Gori T, Schmidt FP, Rao X, Brook FR, Chen LC, Brook RD, Rajagopalan S. Environmental stressors and cardio-metabolic disease: part II–mechanistic insights. European Heart Journal 2017;38(8):557-564. R834797 (Final)
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  • Journal Article Munzel T, Sorensen M, Gori T, Schmidt FP, Rao X, Brook J, Chen LC, Brook RD, Rajagopalan S. Environmental stressors and cardio-metabolic disease: part I–epidemiologic evidence supporting a role for noise and air pollution and effects of mitigation strategies. European Heart Journal 2017;38(8):550-556. R834797 (Final)
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  • Journal Article Newby DE, Mannucci PM, Tell GS, Baccarelli AA, Brook RD, Donaldson K, Forastiere F, Franchini M, Franco OH, Graham I, Hoek G, Hoffmann B, Hoylaerts MF, Kunzli N, Mills N, Pekkanen J, Peters A, Piepoli MF, Rajagopalan S, Storey RF, ESC Working Group on Thrombosis, European Association for Cardiovascular Prevention and Rehabilitation, ESC Heart Failure Association. Expert position paper on air pollution and cardiovascular disease. European Heart Journal 2015;36(2):83-93b. R834797 (2014)
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  • Journal Article Ong CB, Kumagai K, Brooks PT, Brandenberger C, Lewandowski RP, Jackson-Humbles DN, Nault R, Zacharewski TR, Wagner JG, Harkema JR. Ozone-induced type 2 immunity in nasal airways. Development and lymphoid cell dependence in mice. American Journal of Respiratory Cell and Molecular Biology 2016;54(3):331-340. R834797 (2014)
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  • Journal Article Pancras JP, Landis MS, Norris GA, Vedantham R, Dvonch JT. Source apportionment of ambient fine particulate matter in Dearborn, Michigan, using hourly resolved PM chemical composition data. The Science of the Total Environment 2013;448:2-13. R834797 (2013)
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  • Journal Article Rajagopalan S, Brook RD. Personalizing your airspace and your health. Journal of the American College of Cardiology 2015;65(21):2288-2290. R834797 (2014)
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  • Journal Article Rao X, Zhong J, Maiseyeu A, Gopalakrishnan B, Villamena FA, Chen LC, Harkema JR, Sun Q, Rajagopalan S. CD36-dependent 7-ketocholesterol accumulation in macrophages mediates progression of atherosclerosis in response to chronic air pollution exposure. Circulation Research 2014;115(9):770-780. R834797 (2014)
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  • Journal Article Rao X, Patel P, Puett R, Rajagopalan S. Air pollution as a risk factor for type 2 diabetes. Toxicological Sciences 2015;143(2):231-241. R834797 (2014)
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  • Journal Article Rao X, Montresor-Lopez J, Puett R, Rajagopalan S, Brook RD. Ambient air pollution:an emerging risk factor for diabetes mellitus. Current Diabetes Reports 2015;15(6):603. R834797 (2014)
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  • Journal Article Rohr AC, Kamal A, Morishita M, Mukherjee B, Keeler GJ, Harkema JR, Wagner JG. Altered heart rate variability in spontaneously hypertensive rats is associated with specific particulate matter components in Detroit, Michigan. Environmental Health Perspectives 2011;119(4):474-480. R834797 (2014)
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  • Journal Article Sun L, Liu C, Xu X, Ying Z, Maiseyeu A, Wang A, Allen K, Lewandowski RP, Bramble LA, Morishita M, Wagner JG, Dvonch JT, Sun Z, Yan X, Brook RD, Rajagopalan S, Harkema JR, Sun Q, Fan Z. Ambient fine particulate matter and ozone exposures induce inflammation in epicardial and perirenal adipose tissues in rats fed a high fructose diet. Particle and Fibre Toxicology 2013;10:43. R834797 (2013)
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  • Journal Article Vital M, Harkema JR, Rizzo M, Tiedje J, Brandenberger C. Alterations of the murine gut microbiome with age and allergic airway disease. Journal of Immunology Research 2015;2015:892568 (8 pp.). R834797 (2015)
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  • Journal Article Wagner JG, Morishita M, Keeler GJ, Harkema JR. Divergent effects of urban particulate air pollution on allergic airway responses in experimental asthma:a comparison of field exposure studies. Environmental Health 2012;11:45 (13 pp.). R834797 (2014)
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  • Journal Article Wagner JG, Allen K, Yang HY, Nan B, Morishita M, Mukherjee B, Dvonch JT, Spino C, Fink GD, Rajagopalan S, Sun Q, Brook RD, Harkema JR. Cardiovascular depression in rats exposed to inhaled particulate matter and ozone: effects of diet-induced metabolic syndrome. Environmental Health Perspectives 2014;122(1):27-33. R834797 (2013)
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  • Journal Article Wagner JG, Kamal AS, Morishita M, Dvonch JT, Harkema JR, Rohr AC. PM2.5-induced cardiovascular dysregulation in rats is associated with elemental carbon and temperature-resolved carbon subfractions. Particle and Fibre Toxicology 2014;11:25 (10 pp.). R834797 (2014)
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  • Journal Article Wang Y, Eliot MN, Kuchel GA, Schwartz J, Coull BA, Mittleman MA, Lipsitz LA, Wellenius GA. Long-term exposure to ambient air pollution and serum leptin in older adults: results from the MOBILIZE Boston Study. Journal of Occupational and Environmental Medicine 2014;56(9):e73-e77. R834797 (2016)
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  • Journal Article Wellenius GA, Boyle LD, Wilker EH, Sorond FA, Coull BA, Koutrakis P, Mittleman MA, Lipsitz LA. Ambient fine particulate matter alters cerebral hemodynamics in the elderly. Stroke 2013;44(6):1532-1536. R834797 (2016)
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  • Journal Article Wold LE, Ying Z, Hutchinson KR, Velten M, Gorr MW, Velten C, Youtz DJ, Wang A, Lucchesi PA, Sun Q, Rajagopalan S. Cardiovascular remodeling in response to long-term exposure to fine particulate matter air pollution. Circulation:Heart Failure 2012;5(4):452-461. R834797 (2014)
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  • Journal Article Xu X, Liu C, Xu Z, Tzan K, Zhong M, Wang A, Lippmann M, Chen LC, Rajagopalan S, Sun Q. Long-term exposure to ambient fine particulate pollution induces insulin resistance and mitochondrial alteration in adipose tissue. Toxicological Sciences 2011;124(1):88-98. R834797 (2014)
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  • Journal Article Xu X, Liu C, Xu Z, Tzan K, Wang A, Rajagopalan S, Sun Q. Altered adipocyte progenitor population and adipose-related gene profile in adipose tissue by long-term high-fat diet in mice. Life Sciences 2012;90(25-26):1001-1009. R834797 (2014)
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  • Journal Article Xu Z, Xu X, Zhong M, Hotchkiss IP, Lewandowski RP, Wagner JG, Bramble LA, Yang Y, Wang A, Harkema JR, Lippmann M, Rajagopalan S, Chen L-C, Sun Q. Ambient particulate air pollution induces oxidative stress and alterations of mitochondria and gene expression in brown and white adipose tissues. Particle and Fibre Toxicology 2011;8:20 (14 pp.). R834797 (2014)
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  • Journal Article Ying Z, Xu X, Chen M, Liu D, Zhong M, Chen L-C, Sun Q, Rajagopalan S. A synergistic vascular effect of airborne particulate matter and nickel in a mouse model. Toxicological Sciences 2013;135(1):72-80. R834797 (2013)
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  • Journal Article Ying Z, Xu X, Bai Y, Zhong J, Chen M, Liang Y, Zhao J, Liu D, Morishita M, Sun Q, Spino C, Brook RD, Harkema JR, Rajagopalan S. Long-term exposure to concentrated ambient PM2.5 increases mouse blood pressure through abnormal activation of sympathetic nervous system:a role for hypothalamic inflammation. Environmental Health Perspectives 2014;122(1):79-86. R834797 (2013)
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  • Journal Article Yue W, Stolzel M, Cyrys J, Pitz M, Heinrich J, Kreyling WG, Wichmann H-E, Peters A, Wang S, Hopke PK. Source apportionment of ambient fine particle size distribution using positive matrix factorization in Erfurt, Germany. Science of the Total Environment 2008;398(1-3):133-144. R834797 (2016)
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  • Journal Article Zheng Z, Xu X, Zhang X, Wang A, Zhang C, Huttemann M, Grossman LI, Chen LC, Rajagopalan S, Sun Q, Zhang K. Exposure to ambient particulate matter induces a NASH-like phenotype and impairs hepatic glucose metabolism in an animal model. Journal of Hepatology 2013;58(1):148-154. R834797 (2014)
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  • Journal Article Zhong J, Allen K, Rao X, Ying Z, Braunstein Z, Kankanala SR, Xia C, Wang X, Bramble LA, Wagner JG, Lewandowski R, Sun Q, Harkema JR, Rajagopalan S. (2016) Repeated ozone exposure exacerbates insulin resistance and activates innate immune response in genetically susceptible mice. Inhalation Toxicology 2016;28(9):383-392. R834797 (Final)
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  • Journal Article Kumagai K, Lewandowski R, Jackson-Humbles DN, Li N, Van Dyken SJ, Wagner JG, Harkema JR (2016). Ozone-Induced Nasal Type 2 Immunity in Mice Is Dependent on Innate Lymphoid Cells. American Journal of Respiratory Cell and Molecular Biology 2016;54(6):782-791. R834797 (Final)
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  • Journal Article Ong CB, Kumagai K, Brooks PT, Brandenberger C, Lewandowski RP, Jackson-HumblesDN, Nault R, Zacharewski TR, Wagner JG, Harkema JR. (2016) Ozone-Induced Type 2 Immunity in Nasal Airways: Development and Lymphoid Cell Dependence in Mice. American Journal of Respiratory Cell and Molecular Biology 2016;54(3):331-340. R834797 (Final)
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  • Journal Article Ying Z, Allen K, Zhong J, Chen M, Williams KM, Wagner JG, Lewandowski R, Sun Q, Rajagopalan S, Harkema JR. Subacute inhalation exposure to ozone induces systemic inflammation but not insulin resistance in a diabetic mouse model. Inhalation Toxicology 2016;28(4):155-163. R834797 (Final)
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  • Journal Article Harkema JR, Hotchkiss LA, Vetter NA, Jackson-Humbles DN, Lewandowski RP, Wagner JG. Strain Differences in a Murine Model of Air Pollutant-induced Nonatopic Asthma and Rhinitis. Toxicologic Pathology 2017;45(1):161-171. R834797 (Final)
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  • Journal Article Rajagopalan S, Brook RD. (2012) Air Pollution and Type II Diabetes:Mechanistic Insights Diabetes. 2012 Dec;61(12):3037-45. PMCID:PMC3501850. R834797C003 (Final)
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    Journal Article Münzel T, Sørensen M, Gori T, Schmidt FP, Rao X, Brook J, Chen LC, Brook RD, Rajagopalan S. (2016) Environmental stressors and cardio-metabolic disease:part I-epidemiologic evidence supporting a role for noise and air pollution and effects of mitigation strategies. Eur Heart J. 2016 Jul 26. pii:ehw269. PMID:27460892. R834797C003 (Final)
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    Journal Article Münzel T, Sørensen M, Gori T, Schmidt FP, Rao X, Brook FR, Chen LC, Brook RD, Rajagopalan S. (2016) Environmental stressors and cardio-metabolic disease:part II-mechanistic insights.Eur Heart J. 2016 Jul 26. pii:ehw294. [Epub ahead of print] PMID:27460891. R834797C003 (Final)
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    Journal Article Ying Z, Allen K, Zhong J, Chen M, Williams KM, Wagner JG, Lewandowski R, Sun Q, Rajagopalan S, Harkema JR. (2016) Subacute inhalation exposure to ozone induces systemic inflammation but not insulin resistance in a diabetic mouse model. Inhal Toxicol. 2016;28(4):155-63. PMCID:PMC4836866. R834797C003 (Final)
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    Journal Article Carll, A.P., Crespo, S.M., Filho, M.S., Zati, D.H., Coull, B.A., Diaz, E.A., Raimundo, R.D., Jaeger, T.N.G., Ricci-Vitor, A.L., Papapostolou, V., Lawrence, J.E., Garner, D.M., Perry, B.S., Harkema, J.R., and Godleski, J.J. (2017). Inhaled Ambient-level Traffic-derived Particulates Decrease Cardiac Vagal Influence and Baroreflexes and Increase Arrhythmia in a Rat Model of Metabolic Syndrome. Particle and Fibre Toxicology 14, 16. R834797C002 (Final)
    not available
    Journal Article Zhong J, Allen K, Rao X, Ying Z, Braunstein Z, Kankanala SR, Xia C, Wang X, Bramble LA, Wagner JG, Lewandowski R, Sun Q, Harkema JR, Rajagopalan S (2016). Repeated ozone exposure exacerbates insulin resistance and activates innate immune response in genetically susceptible mice. Inhal Toxicol. 28(9):383-92. PubMed PMID:27240593. R834797C002 (2016)
    R834797C002 (Final)
    not available
    Journal Article Subacute inhalation exposure to ozone induces systemic inflammation but not insulin resistance in a diabetic mouse model. Ying Z, Allen K, Zhong J, Chen M, Williams KM, Wagner JG, Lewandowski R, Sun Q, Rajagopalan S, Harkema JR. Inhal Toxicol. 2016;28(4):155-63. R834797C003 (2016)
    R834797C003 (Final)
    not available
    Journal Article Repeated ozone exposure exacerbates insulin resistance and activates innate immune response in genetically susceptible mice. Zhong J, Allen K, Rao X, Ying Z, Braunstein Z, Kankanala SR, Xia C, Wang X, Bramble LA, Wagner JG, Lewandowski R, Sun Q, Harkema JR, Rajagopalan S. Inhal Toxicol. 2016 Aug;28(9):383-92. R834797C003 (2016)
    R834797C003 (Final)
    not available

    Supplemental Keywords:

    Air toxics, metals exposure, SEAS, biostatistics, data management, modeling of multipollutant mixtures, high dimensional correlated data;, Scientific Discipline, Air, ENVIRONMENTAL MANAGEMENT, HUMAN HEALTH, air toxics, Exposure, Health Risk Assessment, Biochemistry, Biology, Risk Assessment, ambient air quality, particulate matter, aerosol particles, susceptible populations, acute cardiovascualr effects, human exposure, physiology, cardiopulmonary, cardiotoxicity, acute exposure

    Relevant Websites:

    http://greatlakesairresearchcenter.org/ Exit

    Progress and Final Reports:

    Original Abstract
  • 2011 Progress Report
  • 2013 Progress Report
  • 2014 Progress Report
  • 2015 Progress Report
  • Final Report
  • Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R834797C001 Cardiometabolic Effects of Exposure to Differing Mixtures and Concentrations of PM2.5 in Obese and Lean Adults
    R834797C002 Cardiometabolic, Autonomic, and Airway Toxicity of Acute Exposures to PM2.5 from Multipollutant Atmospheres in the Great Lakes Region
    R834797C003 Long Term Metabolic Consequences of Exposures to Multipollutant Atmospheres in the Great Lakes Region