using microarrays to monitor gene expression induced by outdoor airborne particulate matter
TRANSCRIPT
IntroductionMethodsResults
Prospects
Using Microarrays to Monitor Gene
Expression Induced by Outdoor Airborne
Particulate Matter
B. Rey de Castro, Sc.D.
WestatRockville, Maryland USA
March 25, 2010
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Outline
1 Introduction
2 Methods
3 Results
4 Prospects
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Outline
1 Introduction
2 Methods
3 Results
4 Prospects
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Genomic Exposure Assessment
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
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?
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Motivation
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Aims
Hypothesis
The organic fraction of PM2.5 alters expression ofgenes related to detoxification, stress response,inflammatory response, apoptosis in normal humanepithelial cells of the small airway
Simple pilot projectObserve gene expression profiles induced by PM2.5collected in BostonIdentify groups of co-expressed genesCorrelate gene expression profiles with season,temperature, dew point, PM mass, PAH concentrationprofile
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Outline
1 Introduction
2 Methods
3 Results
4 Prospects
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
High-Volume Cascade Impactor
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
PUF Sample
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Small Airway Epithelial Cells (SAEC)
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Design Overview
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
DNA Microarray
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Outline
1 Introduction
2 Methods
3 Results
4 Prospects
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Summer vs. Field Blank: SAMs RMA
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Cytochrome P450 Genes
Gene Fold-Change 90 % CICYP1B1 (dioxin-inducible) 4.18 [3.24 : 5.60]CYP1A1 (aromatic-inducible) 3.88 [2.84 : 5.39]CYP2C9 1.36 [1.14 : 1.60]
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Inflammation Genes
Gene Fold-Change 90 % CIinterleukin-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]
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Summary: Gene Expression Response
Scope: 100 genes
Detoxification: strongest
Increased CYP1B1, CYP1A1, CYP2C9
Inflammation: moderate
Increased interleukin-1β, calgranulins A and BIncreased interleukin-1 receptor antagonistDecreased interleukin-8
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Outline
1 Introduction
2 Methods
3 Results
4 Prospects
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Genomic Exposure Assessment
Correlate gene expression with PM exposure
When, WhereSourcesConstituentsOther phenomena
Genes-Environment interactions
Airborne biologic agents?
Surveillance
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Genomic Exposure Assessment
[email protected] Genomic Exposure Assessment @ Gradient
IntroductionMethodsResults
Prospects
Contact
On SlideShare: http://cli.gs/microarrayGradient
B. Rey de Castro, Sc.D.410-929-3583
[email protected] Genomic Exposure Assessment @ Gradient