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Research Experiences and Current Project
Working for a chemical company, I have been studying genetic
toxicants and developing new genotoxicity testing assays for
over ten years, using techniques such as cell culture techniques,
in vitro drug metabolism methods and molecular biology approaches.
More recently, I have studied toxic chemicals for their gene
expression pattern using Affymetrix GeneChip technology.
My current interests are focused on toxicogenomics, an approach
to study the toxicity at global gene expression levels. A chemical
is expected to produce a specific gene expression pattern that
reflects pharmacological and toxicological effects on the target
tissue or cells. Thus, one can obtain valuable information on
the mechanism of action of the chemical. Based on the distinct
gene expression pattern of well-known toxicants, we also may
establish screening methods for chemicals eliciting a specific
toxicity.
The research project I am currently involved in is to investigate
gene expression profiles for neurotoxicants. To date, various
types of chemicals are known to induce neurotoxic effects including
neural degeneration, disruption of brain development, and behavioral
and learning impairments. However, the modes of action of neurotoxicants
are poorly understood mainly due to the limitations of in vivo
model systems. The brain is complex consisting of several different
types of cells and it is not possible to investigate chemical
effects on a specific type of cell within the brain. In addition,
it is difficult to examine neurotoxicant effects at specific
stages of brain development using in vivo models.
One possibility to overcome some of these problems is to develop
appropriate in vitro models of neural development. I am currently
using a SV40-transformed human neural-glial cell line in collaboration
with Dr. Trosko (National Food Safety & Toxicology Center,
Department of Pediatrics and Human Development, Michigan State
University), who has found that SVG cells can undergo differentiation
upon cAMP induction. With this model, I am investigating the
global gene expression changes of SVG cells treated with developmental
neurotoxicants, and correlating these gene expression changes
to morphological changes and cellular markers expression.
The goal of this project is to identify genes involved in manifesting
neurotoxicant effects and to elucidate the mechanisms for these
chemicals.
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