Andrea Baccarelli

Harvard University, Cambridge, Massachusetts, United States

Are you Andrea Baccarelli?

Claim your profile

Publications (312)1496.02 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Air pollution exposure has been linked to impaired cognitive aging, but little is known about biomarkers modifying this association. MicroRNAs (miRNAs) control gene expression and neuronal programming. miRNA levels vary due to single nucleotide polymorphisms (SNPs) in genes processing miRNAs from precursor molecules. Objectives: To investigate whether SNPs in miRNA-processing genes are associated with cognition and modify the relationship between black carbon (BC), marker of traffic-related pollution, and cognitive functions. Methods: 533 Normative Aging Study men (mean±SD 72±7years) were tested ≤4 times (mean=1.7 times) using seven cognitive tests between 1995 and 2007. We tested interactions of 16 miRNA-related SNPs with 1-year average BC from a validated land-use-regression model. We used covariate-adjusted logistic regression for low (≤25) Mini-Mental tate Examination (MMSE) and mixed-effect regression for a global cognitive score combining six other tests. Results: Global cognition was negatively associated with the homozygous minor variant of rs595961 AGO1 (-0.42SD; 95%CI: (-0.71, -0.13)) relative to the major variant. BC-MMSE association was stronger in heterozygous carriers of rs11077 XPO5 (OR=1.99; 95%CI: (1.39, 2.85)) and minor variant carriers of GEMIN4 rs2740348 (OR=1.34; 95%CI: (1.05, 1.7)), compared to their major variant. The BC-global-cognition association was stronger in heterozygous carriers of GEMIN4 rs4968104 (-0.10SD; 95%CI: (-0.18, -0.02)), and GEMIN4 rs910924 (-0.09SD; 95%CI: (-0.17, -0.02)) relative to the major variant. Blood miRNA expression analyses showed associations only of XPO5 rs11077 with miR-9 and miR-96. Conclusions: Carriers of particular miRNA-processing SNPs had higher susceptibility to BC in BC-cognition associations, possibly due to influences on miRNA expression.
    No preview · Article · Mar 2016 · Environment international
  • Source
    Jia Zhong · Golareh Agha · Andrea A. Baccarelli

    Full-text · Article · Jan 2016 · Circulation Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Epidemiological studies have reported associations between particulate matter (PM) concentrations and cancer, respiratory, and cardiovascular diseases. DNA methylation has been identified as a possible link but so far it has only been analyzed in candidate sites. Objectives: To study the association between DNA methylation and short- and mid-term air pollution exposure using genome-wide data, and identify potential biological pathways for additional investigation. Methods: We collected whole blood samples from three independent studies, KORA F3 (2004-05) and F4 (2006-08) from Germany and Normative Aging Study (1999-2007) from the US, and measured genome-wide DNA methylation proportions with the Illumina 450k BeadChip. PM concentration was measured daily at fixed monitoring stations and three different trailing averages were considered and regressed against DNA methylation: 2-day, 7-day and 28-day. Meta-analysis was performed to pool the study-specific results. Results: Random-effect meta-analysis revealed 12 CpG (cytosine-guanine dinucleotide) sites as associated with PM concentration (one for 2-day average, one for 7-day and ten for 28-day) at a genome-wide Bonferroni significance level (p<=7.5E-8); 9 out of these 12 sites expressed increased methylation. Through estimation of I-squared statistics for homogeneity assessment across the studies, four of these sites (annotated in NSMAF, C1orf212, MSGN1, NXN) showed p>0.05 and I(2)<0.5: the site from the 7-day average results and 3 for the 28-day average. Applying False Discovery Rate, p-value<0.05 was observed in 8 and 1819 additional CpGs at 7- and 28-day average PM2.5 exposure respectively. Conclusion: The PM-related CpG sites found in our study suggest novel plausible systemic pathways linking ambient particulate matter exposure to adverse health effect through variations in DNA methylation.
    No preview · Article · Jan 2016 · Environmental Health Perspectives
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: -Exposure to black carbon (BC), a tracer of vehicular-traffic-pollution, is associated with increased blood pressure (BP). Identifying biological factors that attenuate BC effects on BP can inform prevention. We evaluated the role of mitochondrial abundance, an adaptive mechanism compensating for cellular-redox-imbalance, in the BC-BP relationship. Methods and results: -At one or more visits among 675 older men from the Normative Aging Study (observations=1,252), we assessed daily BP and ambient BC levels from a stationary monitor. To determine blood mitochondrial abundance, we used whole blood to analyze mitochondrial-to-nuclear DNA ratio (mtDNA/nDNA) using quantitative polymerase-chain-reaction. Every standard deviation (SD) increase in 28-day BC moving average (MA) was associated with 1.97 mm Hg (95%CI, 1.23-2.72; P<0.0001) and 3.46 mm Hg (95%CI, 2.06-4.87; P<0.0001) higher diastolic and systolic (SBP) BP, respectively. Positive BC-BP associations existed throughout all time windows. BC MAs (5-day to 28-day) were associated with increased mtDNA/nDNA; every SD increase in 28-day BC MA was associated with 0.12 SD (95%CI, 0.03-0.20; P=0.007) higher mtDNA/nDNA. High mtDNA/nDNA significantly attenuated the BC-SBP association throughout all time windows. The estimated effect of 28-day BC MA on SBP was 1.95-fold larger for individuals at the lowest mtDNA/nDNA quartile midpoint (4.68 mm Hg; 95%CI, 3.03-6.33; P<0.0001), compared to the top quartile midpoint (2.40 mm Hg; 95%CI, 0.81-3.99; P=0.003). Conclusions: -In older adults, short- to moderate-term ambient BC levels were associated with increased BP and blood mitochondrial abundance. Our findings indicate that increased blood mitochondrial abundance is a compensatory response and attenuates the cardiac effects of BC.
    Full-text · Article · Dec 2015 · Circulation
  • Source
    Andrea A Baccarelli · Hyang-Min Byun
    [Show abstract] [Hide abstract]
    ABSTRACT: Platelets are critical in the etiology of cardiovascular disease (CVD), and the mitochondria in these cells serve as an energy source for platelet function. Epigenetic factors, especially DNA methylation, have been employed as markers of CVD. Unlike nuclear DNA methylation, mitochondrial DNA (mtDNA) methylation has not been widely studied, in part, due to debate about its existence and role. In this study, we examined platelet mtDNA methylation in relation to CVD. We measured mtDNA methylation in platelets by bisulfite-PCR pyrosequencing and examined associations of CVD with methylation in mitochondrial genes; cytochrome c oxidase (MT-CO1, MT-CO2, and MT-CO3); tRNA leucine 1 (MT-TL1); ATP synthase (MT-ATP6 and MT-ATP8); and NADH dehydrogenase (MT-MD5). We report that CVD patients have significantly higher mtDNA methylation than healthy controls in MT-CO1 (18.53%, P < 0.0001), MT-CO2 (3.33%, P = 0.0001), MT-CO3 (0.92%, P < 0.0001), and MT-TL1 (1.67%, P = 0.0001), which are involved in ATP synthesis. Platelet mtDNA methylation was not related with age, BMI, and race in this study. Our results suggest that platelet mtDNA methylation, which could serve as non-invasive and easy-to-obtain markers, may be implicated in the etiology of CVD.
    Full-text · Article · Dec 2015 · Clinical Epigenetics
  • [Show abstract] [Hide abstract]
    ABSTRACT: Exposure to arsenic early in life has been associated with increased risk of several chronic diseases and is believed to alter epigenetic programming in utero. In the present study, we evaluate the epigenome-wide association of arsenic exposure in utero and DNA methylation in placenta (n = 37), umbilical artery (n = 45) and human umbilical vein endothelial cells (HUVEC) (n = 52) in a birth cohort using the Infinium HumanMethylation450 BeadChip array. Unadjusted and cell mixture adjusted associations for each tissue were examined along with enrichment analyses relative to CpG island location and omnibus permutation tests of association among biological pathways. One CpG in artery (cg26587014) and 4 CpGs in placenta (cg12825509; cg20554753; cg23439277; cg21055948) reached a Bonferroni adjusted level of significance. Several CpGs were differentially methylated in artery and placenta when controlling the false discovery rate (q-value<0.05), but none in HUVEC. Enrichment of hypomethylated CpG islands was observed for artery while hypermethylation of open sea regions were present in placenta relative to prenatal arsenic exposure. The melanogenesis pathway was differentially methylated in artery (Max F P < 0.001), placenta (Max F P < 0.001), and HUVEC (Max F P = 0.02). Similarly, the insulin-signaling pathway was differentially methylated in artery (Max F P = 0.02), placenta (Max F P = 0.02), and HUVEC (Max F P = 0.02). Our results show that prenatal arsenic exposure can alter DNA methylation in artery and placenta but not in HUVEC. Further studies are needed to determine if these alterations in DNA methylation mediate the effect of prenatal arsenic exposure and health outcomes later in life.
    No preview · Article · Nov 2015 · Epigenetics
  • Heather H Burris · Andrea A Baccarelli · Robert O Wright · Rosalind J Wright
    [Show abstract] [Hide abstract]
    ABSTRACT: Preterm birth remains a leading cause of infant mortality and morbidity. Despite decades of research, marked racial and socioeconomic disparities in preterm birth persist. In the US, more than 16% of African American infants are born before 37 weeks of gestation compared to less than 11% of white infants. While income and education differences predict a portion of these racial disparities, income and education are proxies of the underlying causes rather than the true cause. How these differences lead to the pathophysiology remains unknown. Beyond tobacco smoke exposure, most preterm birth investigators overlook environment exposures that often correlate with poverty. Environmental exposures to industrial contaminants track along both socioeconomic and racial/ethnic lines due to cultural variation in personal product use, diet and residential geographical separation. Emerging evidence suggests that environmental exposure to as metals and plasticizers contribute to preterm birth and epigenetic modifications. The extent to which disparities in preterm birth result from interactions between the social and physical environments that produce epigenetic modifications remains unclear. In this review, we highlight studies that report associations between environmental exposures and preterm birth as well as perinatal epigenetic sensitivity to environmental contaminants and socioeconomic stressors.Pediatric Research (2015); doi:10.1038/pr.2015.191.
    No preview · Article · Oct 2015 · Pediatric Research
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The development of the Infinium HumanMethylation450 BeadChip enables epigenome-wide association studies at a reduced cost. One observation of the 450K data is that many CpG sites the beadchip interrogates have very large measurement errors. Including these noisy CpGs will decrease the statistical power of detecting relevant associations due to multiple testing correction. We propose to use intra-class correlation coefficient (ICC), which characterizes the relative contribution of the biological variability to the total variability, to filter CpGs when technical replicates are available. We estimate the ICC based on a linear mixed effects model by pooling all the samples instead of using the technical replicates only. An ultra-fast algorithm has been developed to address the computational complexity and CpG filtering can be completed in minutes on a desktop computer for a 450K data set of over 1000 samples. Our method is very flexible and can accommodate any replicate design. Simulations and a real data application demonstrate that our whole-sample ICC method performs better than replicate-sample ICC or variance-based method. Availability and implementation: CpGFilter is implemented in R and publicly available under CRAN via the R package ‘CpGFilter’. Contact: chen.jun2{at}mayo.edu or xlin{at}hsph.harvard.edu Supplementary information: Supplementary data are available at Bioinformatics online.
    Full-text · Article · Oct 2015 · Bioinformatics
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim: Toxic metals including lead and mercury are associated with adverse pregnancy outcomes. This study aimed to assess the association between miRNA expression in the cervix during pregnancy with lead and mercury levels. Materials & methods: We obtained cervical swabs from pregnant women (n = 60) and quantified cervical miRNA expression. Women's blood lead, bone lead and toenail mercury levels were analyzed. We performed linear regression to examine the association between metal levels and expression of 74 miRNAs adjusting for covariates. Results: Seventeen miRNAs were negatively associated with toenail mercury levels, and tibial bone lead levels were associated with decreased expression of miR-575 and miR-4286. Conclusion: The findings highlight miRNAs in the human cervix as novel responders to maternal chemical exposure during pregnancy.
    Full-text · Article · Sep 2015 · Epigenomics
  • Source

    Full-text · Dataset · Sep 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Current studies of environmental health suggest a link between air pollution components, such as particulate matter (PM), and various diseases. However, the specific genes and regulatory mechanisms implicated in PM-induced diseases remain largely unknown. Epigenetic systems such as covalent modification of histones in chromatin may mediate environmental factors in gene regulation. Investigating the relationships between PM exposure and histone modification status may help understand the mechanisms underlying environment-associated health conditions. Methods: In this study, we obtained genome-wide profiles of H3K27ac (histone 3 lysine 27 acetylation), known to be an active gene regulatory histone modification marker, in blood samples collected from four Chinese individuals exposed to high or low PM2.5 (particles with diameters up to 2.5 μm). Results: The genome-wide chromatin immunoprecipitation sequencing (ChIP-Seq) data indicated a comprehensive differential H3K27ac landscape across the individual genomes, which was associated with high PM2.5. Moreover, a substantial number of these PM2.5-associated differential H3K27ac markers were in genes involved in immune cell activation, potentially linking these epigenetic changes with air pollution-induced immune and inflammatory responses. Conclusions: Our study provides the first genome-wide characterization of H3K27ac profiles in individuals subjected to different exposure levels of PM2.5. Future systematic investigations of the relationships between air pollutants and histone modifications in large population samples are warranted to elucidate the contributions of histone modifications to environment-associated diseases.
    Full-text · Article · Aug 2015 · Environmental Health
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic inflammation plays a key role in cancer etiology. DNA methylation modification, one of the epigenetic mechanisms regulating gene expression, is considered a hallmark of cancer. Human and animal models have identified numerous links between DNA methylation and inflammatory biomarkers. Our objective was to prospectively and longitudinally examine associations between methylation of four inflammatory genes and cancer risk. We included 795 Normative Aging Study participants with blood drawn 1-4 times from 1999-2012 (median follow up 10.6 years). Promoter DNA methylation of IL-6, ICAM-1, IFN, and TLR2 in blood leukocytes was measured using pyrosequencing at multiple CpG sites and averaged by gene for data analysis. We used Cox regression models to examine prospective associations of baseline and time-dependent methylation with cancer risk, and compared mean methylation differences over time between cancer cases and cancer-free participants. Baseline IFN hypermethylation was associated with all-cancer (HR=1.49, p=0.04) and prostate cancer incidence (HR=1.69, p=0.02). Baseline ICAM-1 and IL-6 hypermethylation were associated with prostate cancer incidence (HR=1.43, p=0.02; HR=0.70, p=0.03 respectively). In our time-dependent analyses, IFN hypermethylation was associated with all-cancer (HR=1.79, p=0.007) and prostate cancer (HR=1.57, p=0.03) incidence; and ICAM-1 and IL-6 hypermethylation were associated with prostate cancer incidence (HR=1.39, p=0.02; HR=0.69, p=0.03 respectively). We detected significant ICAM-1 hypermethylation in cancer cases (p=0.0003) 10-13 years pre-diagnosis. Hypermethylation of IFN and ICAM-1 may play important roles in early carcinogenesis, particularly that of prostate cancer. These methylation changes could inform the development of early detection biomarkers and potential treatments of inflammation-related carcinogenesis. Copyright © 2015, American Association for Cancer Research.
    Full-text · Article · Aug 2015 · Cancer Epidemiology Biomarkers & Prevention
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prenatal smoke exposure, maternal obesity, aberrant fetal growth, and preterm birth are all risk factors for offspring metabolic syndrome. Cord blood aryl-hydrocarbon receptor repressor (AHRR) DNA methylation is responsive to maternal smoking during pregnancy. AHRR serves not only to inhibit aryl-hydrocarbon receptor (AHR) transcription, which is involved in mediating xenobiotic metabolism, but it is also involved in cell growth and differentiation. Other than maternal smoking, other predictors of offspring AHRR DNA methylation status remain unknown; we sought to identify them among newborns. We enrolled pregnant women in the PROGRESS birth cohort in Mexico City. Using pyrosequencing, we analyzed DNA methylation of three CpG sites within the AHRR gene promoter from the umbilical cord blood of 531 infants. We used generalized estimating equations to account for the correlation of DNA methylation between CpG sites. Multivariable models were used to adjust for maternal age, BMI, education, parity, smoke-exposure, infant sex, gestational age, and birth weight-for-gestational age. AHRR DNA methylation was positively associated with maternal BMI (P=0.0009) and negatively associated with the length of gestation (P<0.0001) and birth weight-for-gestational age (P<0.0001). AHRR DNA methylation was 2.1% higher in offspring of obese vs. normal weight mothers and 3.1 higher in preterm vs. term infants, representing a third and a half standard deviation differences in methylation. In conclusion, offspring AHRR DNA methylation was associated with maternal obesity during pregnancy as well as infant gestational age and birth weight-for-gestational age. Further work to discover the health impacts of altered AHRR DNA methylation is warranted.
    No preview · Article · Aug 2015 · Epigenetics: official journal of the DNA Methylation Society
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Short-term exposure to particulate matter (PM) is associated with increased blood pressure (BP) in epidemiological studies. Understanding the impact of specific PM components on BP is essential in developing effective risk-reduction strategies. We investigated the association between endotoxin and β-1,3-d-Glucan-two major biological PM components-and BP. We also examined whether vascular endothelial growth factor, a vasodilatory inflammatory marker, modified these associations. We conducted a single-blind, randomized, crossover trial of controlled human exposure to concentrated ambient particles with 50 healthy adults. Particle-associated-endotoxin and β-1,3-d-Glucan were sampled using polycarbonate-membrane-filters. Supine resting systolic BP and diastolic BP were measured pre-, 0.5-hour post-, and 20-hour postexposure. Urine vascular endothelial growth factor concentration was determined using enzyme-linked immunosorbant assay and creatinine-corrected. Exposures to endotoxin and β-1,3-d-Glucan for 130 minutes were associated with increases in BPs: at 0.5-hour postexposure, every doubling in endotoxin concentration was associated with 1.73 mm Hg higher systolic BP (95% confidence interval, 0.28, 3.18; P=0.02) and 2.07 mm Hg higher diastolic BP (95% confidence interval, 0.74, 3.39; P=0.003); every doubling in β-1,3-d-Glucan concentration was associated with 0.80 mm Hg higher systolic BP (95% confidence interval, -0.07, 1.67; P=0.07) and 0.88 mm Hg higher diastolic BP (95% confidence interval, 0.09, 1.66; P=0.03). Vascular endothelial growth factor rose after concentrated ambient particle endotoxin exposure and attenuated the association between endotoxin and 0.5-hour postexposure diastolic BP (Pinteraction=0.02). In healthy adults, short-term endotoxin and β-1,3-d-Glucan exposures were associated with increased BP. Our findings suggest that the biological PM components contribute to PM-related cardiovascular outcomes, and postexposure vascular endothelial growth factor elevation might be an adaptive response that attenuates these effects. © 2015 American Heart Association, Inc.
    Full-text · Article · Jun 2015 · Hypertension
  • [Show abstract] [Hide abstract]
    ABSTRACT: Transposable elements (TE) comprise half of the human genome. LINE-1 and ALU are the most common TE, and they have been used to assess changes in the DNA methylation of repetitive elements in response to intrinsic and extrinsic cellular events. Pyrosequencing(®) is a real-time sequencing technology that enables quantitative assessment of TE methylation at single-base resolution. In Pyrosequencing, a region of interest is first amplified from bisulfite-converted DNA by polymerase chain reaction (PCR), before PCR amplicons are rendered single stranded and annealed with the Pyrosequencing primer prior to sequencing. In this chapter, we provide an overview of the analysis of repetitive element DNA methylation by bisulfite Pyrosequencing, and we describe a protocol that can be used for such purposes.
    No preview · Article · Jun 2015 · Methods in molecular biology (Clifton, N.J.)
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To examine the association of maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with anthropometry in the offspring of mothers with gestational diabetes mellitus (GDM). We performed a retrospective cohort study in 1263 GDM mother-child pairs. General linear models and Logistic regression models were used to assess the single and joint associations of maternal pre-pregnancy BMI (normal weight, overweight, and obesity) and GWG (inadequate, adequate and excessive GWG) with anthropometry and overweight status in the offspring from birth to 1-5 years old. Maternal pre-pregnancy BMI and GWG were positively associated with birth weight for gestational age Z score and birth weight for length for gestational age Z score at birth, and weight for age Z score, length/height for age Z score, and weight for length/height Z score at of 1-5 years old offspring. Maternal pre-pregnancy overweight, obesity, and excessive GWG were associated with increased risks of large for gestational age [ORs 95% CIs = 1.87 (1.37-2.55), 2.98 (1.89-4.69), and 2.93 (2.07-4.13), respectively] and macrosomia [ORs 95% CIs = 2.06 (1.50-2.84), 2.89 (1.78-4.70), and 2.84 (1.98-4.06), respectively] at birth and childhood overweight at 1-5 years old [ORs 95% CIs = 1.26 (0.92-1.73), 1.96 (1.24-3.09), and 1.59 (1.15-2.21), respectively]. Offspring born to GDM mothers with pre-pregnancy overweight/obesity or excessive GWG were associated with increased risks of large for gestational age and macrosomia at birth, and childhood overweight at 1-5 years old, compared with those born to GDM mothers with pre-pregnancy normal weight and adequate GWG.
    Full-text · Article · Jun 2015 · PLoS ONE
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aims. We describe a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify and compare simultaneously global methylation and hydroxymethylation in human DNA of different tissues. Materials and Methods. Blood and saliva DNA from fourteen volunteers was processed for epigenetic endpoints using LC-MS/MS and PCR-pyrosequencing technology. Results. Global DNA methylation was significantly lower in saliva (mean 4.61% ± 0.80%), compared to blood samples (5.70% ± 0.22%). In contrast, saliva (0.036% ± 0.011%) revealed significantly higher hydroxymethylation compared to blood samples (mean 0.027% ± 0.004%). Whereas we did not find significant correlations for both epigenetic measures between the tissues, a significant association was observed between global methylation and global hydroxymethylation in saliva DNA. Neither LINE-1 nor Alu elements of blood and saliva correlated, nor were they correlated with the DNA hydroxymethylation of blood or saliva, respectively. Conclusion. Global DNA methylation and hydroxymethylation of cytosine can be quantified simultaneously by LC-MS/MS. Saliva DNA cannot be considered as a surrogate for blood DNA to study epigenetic endpoints.
    Full-text · Article · Jun 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNAs (miRNAs) are post-transcriptional gene suppressors and potential mediators of environmental effects. In addition to human miRNAs, viral miRNAs expressed from latent viral sequences are detectable in human cells. In a highly exposed population in Beijing, China, we evaluated the associations of particulate air pollution exposure on blood miRNA profiles. The Beijing Truck Driver Air Pollution Study (BTDAS) included 60 truck drivers and 60 office workers. We investigated associations of short-term air pollution exposure, using measures of personal PM2.5 and (Elemental Carbon) EC, and ambient PM10, with blood NanoString-nCounter miRNA profiles at two exams separated by one to two weeks. No miRNA was significantly associated with personal PM2.5 at a false discovery rate (FDR) of 20%. Short-term ambient PM10 was associated with the expression of 12 miRNAs in office workers only (FDR <20%). Short-term EC was associated with differential expression of 46 human and seven viral miRNAs, the latter including three and four viral miRNAs in office workers and truck drivers, respectively. EC-associated miRNAs differed between office workers and truck drivers with significant effect modification by occupational group. Functional interaction network analysis suggested enriched cellular proliferation/differentiation pathways in truck drivers and pro-inflammation pathways in office workers. Short-term EC exposure was associated with the expression of human and viral miRNAs that may influence immune responses and other biological pathways. Associations between EC exposure and viral miRNA expression suggest that latent viral miRNAs are potential mediators of air pollution-associated health effects. PM2.5/PM10 exposures showed no consistent relationships with miRNA expression.
    Full-text · Article · Jun 2015 · Environmental Health Perspectives
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent advances in estimating fine particle (PM2.5) ambient concentrations use daily satellite measurements of aerosol optical depth (AOD) for spatially and temporally resolved exposure estimates. Mexico City is a dense megacity that differs from other previously modeled regions in several ways: it has bright land surfaces, a distinctive climatological cycle, and an elevated semi-enclosed air basin with a unique planetary boundary layer dynamic. We extend our previous satellite methodology to the Mexico City area, a region with higher PM2.5 than most US and European urban areas. Using a novel 1 km resolution AOD product from the MODIS instrument, we constructed daily predictions across the greater Mexico City area for 2004-2014. We calibrated the association of AOD to PM2.5 daily using municipal ground monitors, land use, and meteorological features. Predictions used spatial and temporal smoothing to estimate AOD when satellite data were missing. Our model performed well, resulting in an out-of-sample cross validation R2 of 0.724. Cross-validated root mean squared prediction error (RMSPE) of the model was 5.55 μg/m3. This novel model reconstructs long- and short-term spatially resolved exposure to PM2.5 for epidemiological studies in Mexico City.
    Full-text · Article · Jun 2015 · Environmental Science & Technology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recurrent, rapidly growing nasal polyps are hallmarks of aspirin-exacerbated respiratory disease (AERD), though the mechanisms of polyp growth have not been identified. Fibroblasts are intimately involved in tissue remodeling, and the growth of fibroblasts is suppressed by prostaglandin E2 (PGE2), which elicits antiproliferative effects mediated through the E Prostanoid (EP)2 receptor. We now report that cultured fibroblasts from the nasal polyps of subjects with AERD resist this antiproliferative effect. Fibroblasts from polyps of AERD subjects resisted the antiproliferative actions of PGE2 and a selective EP2 agonist (P<0.0001 at 1µM) compared with nasal fibroblasts from aspirin tolerant control subjects undergoing polypectomy or from healthy control subjects undergoing concha bullosa resections. Cell surface expression of the EP2 receptor protein was lower in fibroblasts from AERD subjects than in fibroblasts from healthy controls and aspirin-tolerant subjects (P<0.01 for both). Treatment of the fibroblasts with trichostatin A (TSA), a histone deacetylase inhibitor, significantly increased EP2 receptor mRNA in fibroblasts from AERD and aspirin-tolerant subjects, but had no effect on COX-2, EP4 and mPGES1 mRNA levels. Histone acetylation (H3K27ac) at the EP2 promoter correlated strongly with baseline EP2 mRNA (r=0.80, P<0.01). These studies suggest that the EP2 promotor is under epigenetic control and one explanation for PGE2 resistance in AERD is an epigenetically mediated reduction of EP2 receptor expression which could contribute to the refractory nasal polyposis typically observed in this syndrome.
    No preview · Article · Jun 2015 · American Journal of Respiratory Cell and Molecular Biology

Publication Stats

8k Citations
1,496.02 Total Impact Points

Institutions

  • 2008-2015
    • Harvard University
      • Department of Environmental Health
      Cambridge, Massachusetts, United States
    • Ospedale Maggiore Carlo Alberto Pizzardi di Bologna
      Bolonia, Emilia-Romagna, Italy
  • 2007-2015
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2000-2014
    • University of Milan
      • • Department of Occupational and Environmental Health
      • • Department of Medical Sciences
      • • Istituto Di Scienze Endocrine
      Milano, Lombardy, Italy
  • 2013
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
    • Boston University
      Boston, Massachusetts, United States
  • 2012
    • Università degli Studi di Sassari
      Sassari, Sardinia, Italy
    • Boston College, USA
      Boston, Massachusetts, United States
  • 2009
    • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
      • Occupational Medicine 1
      Milano, Lombardy, Italy
  • 2002-2008
    • National Institutes of Health
      • • Division of Cancer Epidemiology and Genetics
      • • Branch of Genetic Epidemiology
      Maryland, United States
  • 2003-2006
    • National Cancer Institute (USA)
      • • Division of Cancer Epidemiology and Genetics
      • • Genetic Epidemiology
      Bethesda, MD, United States
    • Università degli Studi del Sannio
      Benevento, Campania, Italy
  • 2001-2004
    • NCI-Frederick
      Maryland, United States