ARB Research Seminar

This page updated June 19, 2013

Mechanism and Modeling for Particle-Induced Inflammation

Henry Jay Forman, Ph.D., School of Natural Sciences, University of California, Merced

May 18, 2010
Cal EPA Headquarters, 1001 "I" Street, Sacramento, CA

Presentation

Overview

Epidemiologists predict that particulate matter in air pollution causes 60,000 deaths per year in the United States.

As frightening a statistic as that is, the number is small compared with the hospitalizations for air pollution-induced pulmonary and cardiovascular problems and lost days from work and school. While epidemiologists, statisticians, toxicologists and economists tell us much of what needs to be addressed to reduced this public health menace, an understanding of the molecular mechanisms by which particles cause lung inflammation and injury would be of great additional benefit in formulating regulation of atmospheric emissions to improve public health.

The goal of our studies is to provide a mechanistic basis for assessing the health threat from particles in air pollution by defining the physico-chemical characteristics of particles that contribute to lung inflammation, their interaction with cells and lung, and the testing of a novel hypothesis for the mechanism underlying the early inflammatory response in lungs to low level particle exposure. Our multidisciplinary team approach, using tools from geochemistry, materials science, biochemistry, molecular biology, pathology, and statistics, will combine mechanistic and translational studies of how the chemistry of particles causes lung inflammation and provide precise scientific evidence that would significantly enhance the scientific basis for regulation of atmospheric emissions and improve public health.

We plan to determine the surface chemistry of particles that causes cell membrane damage and inflammation in cells and lungs and whether this is dependent upon activation of a novel oxidative stress signaling pathway. The predictability of lung pathology from cellular models will be tested using an iterative experimental strategy. We will characterize ambient particles using a variety of spectroscopic and ultramicroscopic methods and then use that information to design well characterized model particles, test how these components activate processes within the cell that result in the production of inflammatory mediators in cells and lungs. Both control and sensitized mice will be exposed to mimic normal versus asthmatic susceptibility to particles. Using drugs already approved for human diseases in our experimental models, we may even be able to provide a rationale for pharmacological prevention of particle-induced inflammation. Nonetheless, our primary goal is obtaining data that will be used to improve public health.

Speaker Biography

Henry Jay Forman, Ph.D, is Founding Faculty and Professor of Biochemistry and Chemistry at the University of California, Merced and Adjunct Professor of Gerontology at the University of Southern California. After obtaining his Ph.D from Columbia University and a post-doctoral fellowship at Duke University, professor Forman held faculty positions in biochemistry, physiology, pathology, pediatrics, molecular pharmacology and toxicology at the University of Pennsylvania, USC, and University of Alabama at Birmingham. At UAB, he was Chairman of Environmental Health Sciences. Dr. Forman is the Governor's appointed scientist on the Governing Board of the San Joaquin Valley Air Pollution Control District. Dr. Forman's expertise is in the areas of oxidative stress and signal transduction, and he has over 200 publications. He has been an invited lecturer at numerous national and international symposia and is currently the Associate Editor for Reviews for Free Radical Biology & Medicine and Treasurer of the Society for Free Radical Research International. Professor Forman did pioneering work on mitochondrial reactive oxygen species production, regulation of antioxidant defenses, and the role of oxidants in cell signaling. For over thirty years, Dr. Forman has focused his studies on the role of oxidants in lung function and disease.


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