Biological Assessment of the Toxicity of PM and PM Components

EPA Grant Number: R832417C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R832417
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Johns Hopkins Particulate Matter Research Center
Center Director: Samet, Jonathan M.
Title: Biological Assessment of the Toxicity of PM and PM Components
Investigators: Spannhake, Ernst , DeCastro, Rey , Garcia, Joe , Irizarry, Rafael , Natarajan, Viswanathan
Current Investigators: Spannhake, Ernst , DeCastro, Rey , Garcia, Joe , Irizarry, Rafael , Natarajan, Viswanathan , Vinasco, Liliana Moreno , Wang, Ting
Institution: The Johns Hopkins University , University of Chicago
EPA Project Officer: Hunt, Sherri
Project Period: October 1, 2005 through September 30, 2010
Project Amount: Refer to main center abstract for funding details.
RFA: Particulate Matter Research Centers (2004) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

This project will complement the epidemiologic analyses and state-of the art characterization of US city-specific PM and other pollutants by defining the comparative pathobiologic cardiopulmonary responses to inhaled PM exposure.

Approach:

We will utilize standard toxicologic assessment and high through-put toxicogenomic approaches, to gauge the relative toxicity of PM collected in regions where particles have greater and lesser effects on health outcomes. Project 3 will address potential limitations by integrating state-of-the-art genomic technologies with traditional and complementary toxicologic assessment. To exploit comparisons of pathobiologic cardiopulmonary responses to respirable airborne PM, in Phase I, we will optimize a battery of well-developed in vitro (human) and in vivo (murine) bioassays including multiple cytokines, indicators of reactive oxygen/nitrogen species burden (ROS/RNS), and biomarkers of vascular and cardiac dysfunction for assessing particle toxicity. For this purpose, we will use a set of particles having differing characteristics: standard NIOSH urban PM, Baltimore tunnel PM, ambient Baltimore air PM, New York City air PM. We will use oligonucleotide-based microarrays to address the hypothesis that gene expression profiles in human lung epithelium, murine lung and cardiac tissues, induced by respirable PM, are dependent on the fraction of pollutants bound to the respirable PM. In Phase II, we will survey PM fractions from a number of US sites with this battery, selected according to the sampling plan developed in Project 1, and apply the screening methodologies optimized in Phase I to identify sites with the greatest pathobiologic effects and relate these responses to observed adverse human health effects. Phase III will focus on a smaller number of sites showing the greatest PM toxicity and initiate mechanistic studies using transgenic prototypes, in vitro molecular dissection of signal transduction pathways, and extensive gene profiling.

Expected Results:

The multidisciplinary integration of approaches in Project 3 will lend insight into the interpretation of what constitutes an adverse effect, and accelerate our understanding of the characteristics of PM that determine their toxicity.

Publications and Presentations:

Publications have been submitted on this subproject: View all 12 publications for this subprojectView all 69 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 4 journal articles for this subprojectView all 44 journal articles for this center

Supplemental Keywords:

toxicogenomics, expression profiling, reactive oxygen species, cytokines,, RFA, Health, Scientific Discipline, Air, particulate matter, Health Risk Assessment, Epidemiology, Risk Assessments, atmospheric particulate matter, acute cardiovascular effects, long term exposure, atmospheric particles, toxicogenomic approaches, airway disease, ambient particle health effects, human exposure, ultrafine particulate matter, atmospheric aerosol particles, toxicologic assessment, PM, aersol particles, cardiovascular disease

Progress and Final Reports:

2006 Progress Report
2007 Progress Report
2008 Progress Report
2009 Progress Report
Final Report


Main Center Abstract and Reports:

R832417    Johns Hopkins Particulate Matter Research Center

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832417C001 Estimation of the Risks to Human Health of PM and PM Components
R832417C002 PM Characterization and Exposure Assessment (Project 2)
R832417C003 Biological Assessment of the Toxicity of PM and PM Components