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Using Microarrays to Monitor Gene Expression Induced by Outdoor Airborne Particulate Matter

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Using Microarrays to Monitor Gene Expression Induced by Outdoor Airborne Particulate Matter

  1. 1. Introduction Methods Results Prospects Using Microarrays to Monitor Gene Expression Induced by Outdoor Airborne Particulate Matter B. Rey de Castro, Sc.D. Westat Rockville, Maryland USA March 25, 2010 reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  2. 2. Introduction Methods Results Prospects Outline 1 Introduction 2 Methods 3 Results 4 Prospects reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  3. 3. Introduction Methods Results Prospects Outline 1 Introduction 2 Methods 3 Results 4 Prospects reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  4. 4. Introduction Methods Results Prospects Genomic Exposure Assessment reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  5. 5. Introduction Methods Results Prospects Particulate Matter PM2.5: ≤ 2.5µm aerodynamic diameter ”Fine” fraction Carbonaceous combustion by-product Deeply respirable Vehicle for adsorbed pollutants Organics, metals Health effects Cause? reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  6. 6. Introduction Methods Results Prospects Motivation reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  7. 7. Introduction Methods Results Prospects Aims Hypothesis The organic fraction of PM2.5 alters expression of genes related to detoxification, stress response, inflammatory response, apoptosis in normal human epithelial cells of the small airway Simple pilot project Observe gene expression profiles induced by PM2.5 collected in Boston Identify groups of co-expressed genes Correlate gene expression profiles with season, temperature, dew point, PM mass, PAH concentration profile reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  8. 8. Introduction Methods Results Prospects Outline 1 Introduction 2 Methods 3 Results 4 Prospects reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  9. 9. Introduction Methods Results Prospects High-Volume Cascade Impactor reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  10. 10. Introduction Methods Results Prospects PUF Sample reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  11. 11. Introduction Methods Results Prospects Small Airway Epithelial Cells (SAEC) reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  12. 12. Introduction Methods Results Prospects Design Overview reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  13. 13. Introduction Methods Results Prospects DNA Microarray reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  14. 14. Introduction Methods Results Prospects Outline 1 Introduction 2 Methods 3 Results 4 Prospects reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  15. 15. Introduction Methods Results Prospects Summer vs. Field Blank: SAMs RMA reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  16. 16. Introduction Methods Results Prospects Cytochrome P450 Genes Gene Fold-Change 90 % CI CYP1B1 (dioxin-inducible) 4.18 [3.24 : 5.60] CYP1A1 (aromatic-inducible) 3.88 [2.84 : 5.39] CYP2C9 1.36 [1.14 : 1.60] reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  17. 17. Introduction Methods Results Prospects Inflammation Genes Gene Fold-Change 90 % CI interleukin-1β 1.63 [1.48 : 1.80] calgranulin A 1.62 [1.28 : 2.08] interleukin-1 receptor antagonist 1.50 [1.34 : 1.70] calgranulin B 1.48 [1.22 : 1.79] interleukin-8 -1.64 [-1.17 : -2.25] reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  18. 18. Introduction Methods Results Prospects Summary: Gene Expression Response Scope: 100 genes Detoxification: strongest Increased CYP1B1, CYP1A1, CYP2C9 Inflammation: moderate Increased interleukin-1β, calgranulins A and B Increased interleukin-1 receptor antagonist Decreased interleukin-8 reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  19. 19. Introduction Methods Results Prospects Outline 1 Introduction 2 Methods 3 Results 4 Prospects reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  20. 20. Introduction Methods Results Prospects Genomic Exposure Assessment Correlate gene expression with PM exposure When, Where Sources Constituents Other phenomena Genes-Environment interactions Airborne biologic agents? Surveillance reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  21. 21. Introduction Methods Results Prospects Genomic Exposure Assessment reyDecastro@westat.com Genomic Exposure Assessment @ Gradient
  22. 22. Introduction Methods Results Prospects Contact On SlideShare: http://cli.gs/microarrayGradient B. Rey de Castro, Sc.D. 410-929-3583 reyDecastro@westat.com Genomic Exposure Assessment @ Gradient

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