Dr. Shu Chien will provide a DNA microarray technology core for the screening of the effects of various environmental toxins studied in the Superfund application. The DNA microarray system, which was developed by Dr. Konan Peck of the Institute of Biomedical Sciences of Academia Sinica in Taiwan, involves the use of filters that can accommodate up to 9,600 EST probes. Dr. Chien has performed preliminary studies in collaboration with Dr. Peck on the effects of mechanical shear stress on gene expression using this system. The results indicate the selective up-regulation of a number of DNA damage and repair genes and genes encoding for cytokines and transcription factors. Dr, Chien has set up such a system for his research activities. It is proposed that, under this Superfund grant, we will set up two dedicated microarray systems (including spotting machines) for the identification of genes that respond to various toxicants studied in the research projects. In this Core, DNA microarrays will be developed for several species, including human, mouse, fission yeast and Arabidopsis, as well as other plants or microorganisms that can serve as candidate species for remediation. The microarrays will be configured to emphasize environmentally sensitive genes. A unique feature of the Core is the ability to customize the service according to the needs of the investigators in this program. Dr. Chien's laboratory in the Department of Bioengineering is interested in the molecular mechanisms by which various types of stresses induce signal transduction and gene expression in cells. The types of stresses being studied involve mechanical forces, ultraviolet irradiation, and high temperature. The types of cells being investigated include vascular endothelial cells and smooth muscle cells, osteoblasts, chondrocytes, etc. Several signaling mechanisms are being studied, e.g., the mitogen activated protein kinase pathways (including the ERK, JNK, and p38) as well as the upstream sensors (e.g., receptor tyrosine kinases and integrins) and the downstream genes (e.g., those involved in cell adhesion, proliferation, and apoptosis). The expertise on signaling mechanisms and gene regulation will provide an intellectual basis for interaction between Core A and the various research projects in this program.
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