Grantee Research Project Results

2009 Progress Report: Development of Molecular Biomarkers to Measure Environmentally Induced Immune Responses

EPA Grant Number: R832947
Title: Development of Molecular Biomarkers to Measure Environmentally Induced Immune Responses
Investigators: Miller, Lisa A. , Gern, James , Joad, Jesse
Current Investigators: Miller, Lisa A. , Gilliland, Frank D. , Abel, Kristina , Margolis, Helene , Gern, James , Joad, Jesse
Institution: University of California - Davis
EPA Project Officer: Callan, Richard
Project Period: June 15, 2006 through June 14, 2009 (Extended to December 14, 2011)
Project Period Covered by this Report: June 15, 2009 through June 14,2010
Project Amount: $712,423
RFA: Early Indicators of Environmentally Induced Disease (2004) RFA Text | Recipients Lists
Research Category: Human Health

Objective:

The objective of this study is to establish a panel of immune biomarkers that will be used to detect environmentally induced disease in humans, focusing on parameters of allergy and asthma. The panel of immune biomarkers will be developed by completion of the following two specific aims:

Develop a high-throughput quantitative RT-PCR assay for leukocyte cluster of differentiation markers to measure key immune cell populations associated with allergy and asthma in small biological samples.
Develop a high-throughput quantitative RT-PCR assay for key cytokine markers associated with allergy and asthma to measure immune cell function in small biological samples.

Progress Summary:

A goal for Year 04 was to complete mRNA analysis of infant rhesus monkey peripheral blood samples, using the 26 immune biomarkers that have been designed and tested in our laboratory. We have thus far completed the analysis of 10 immune biomarkers for one set of 24 animals, and have expanded our analysis to a second cohort of 12 animals in a comparative fashion. This alternative plan was taken in order to address important questions related to susceptible windows for immune development, and is expected to provide a secondary data set that will yield a separate publication from our original analysis. In light of recent studies in the area of toll-like receptors, we have also generated a reagent for toll-like receptor 4 and plan to add toll-like receptor 3 and toll-like receptor 5 in this current funding year.

Overall, our findings in this reporting period continue show age and exposure dependent effects on immune biomarker expression in peripheral blood. Our preliminary findings also demonstrate that there is a narrow developmental window of susceptibility with regards to impact of exposure on immune biomarkers. We will continue to evaluate our peripheral blood samples for modulation of additional immune biomarkers by allergen and air pollutant exposure, using reagents designed during the course of this project.

Future Activities:

In the no-cost extension period of this project, we will continue to focus our efforts on completing immune biomarker expression analysis on infant rhesus monkey peripheral blood samples, such that all of the targets are evaluated in the context of exposure and age. The overall goal will be to determine which immune markers are most susceptible to exposure, and also identify specific windows of development that exhibit the most change. With the addition of more data, we have resubmitted the manuscript from our previous progress report to a different journal for review. Our goal is to complete at least two manuscripts during this time period.

Journal Articles on this Report : 1 Displayed | Download in RIS Format

Publications Views
Other project views:	All 6 publications	4 publications in selected types	All 4 journal articles

Publications
Type	Citation	Project	Document Sources
Journal Article	Chou DL, Gerriets JE, Schelegle ES, Hyde DM, Miller LA. Increased CCL24/eotaxin-2 with postnatal ozone exposure in allergen-sensitized infant monkeys is not associated with recruitment of eosinophils to airway mucosa. Toxicology and Applied Pharmacology 2011;257(3):309-318.	R832947 (2007) R832947 (2009) R832947 (Final)	Abstract from PubMed Full-text: Science Direct - Full text HTML Exit Abstract: Science Direct -Abstract Exit Other: Science Direct PDF Exit

Supplemental Keywords:

immunology, ozone, indoor air, health effects, susceptibility, RFA, Health, Air, Scientific Discipline, PHYSICAL ASPECTS, HUMAN HEALTH, Susceptibility/Sensitive Population/Genetic Susceptibility, Health Risk Assessment, Physical Processes, Risk Assessments, particulate matter, genetic susceptability, Environmental Chemistry, Allergens/Asthma, Health Effects, Environmental Monitoring, sensitive populations, health risks, chemical characteristics, airway inflammation, asthma indices, asthma triggers, asthma, aerosol composition, airborne particulate matter, human exposure, ambient air monitoring, environmental risks, second hand smoke, atmospheric particles, atmospheric aerosol particles, particulates, exposure, atmospheric particulate matter, airborne pollutants, allergic response, ambient air quality, air pollution, human health risk, human susceptibility, air toxics, inhalation, airway disease

Progress and Final Reports:

Original Abstract

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.