The Signal Transduction Core consists of 15 members from five departments at the RWJMS and RU. It brings together individuals with expertise in cellular and molecular toxicology with signal transduction as a theme. Members of the Core conduct research that is supported by over $2 million annually in peer reviewed grants, In addition, approximately $250,000 is received annually for peer- reviewed training and non-peer reviewed research activities. Core II investigators authored over 200 publications during the last five years. As a result of collaborations, members of the core jointly published 42 papers. Starting with Exploratory Research Funds and shared resource support, the Core members generated the data to submit a P01 application to NIEHS. The Center provided additional pilot studies to enhance the data base and the grant (1 P0l ES-06897) which has been funded. This core focuses on areas of investigation related to how xenobiotics modulate or interfere with cellular signal transduction processes. Research areas range from examining the interaction of xenobiotics with cell surface receptors and membrane proteins, to studying receptor-associated protein kinases, transcription factors, and interaction of metabolites with DNA. Specific areas of investigation include the analysis of mechanisms by which: xenobiotics alter membrane receptors (J. Laskin, Gallo), xenobiotic transport/multidrug resistance proteins operate (Hait), oxidants induce alterations in signaling pathways utilizing protein kinases and phosphatases (Toledano, Yurkow, Witz, Goldstein), reactive oxygen and reactive nitrogen intermediates affect cellular signaling (Denhardt, Heck, J. Laskin, D. Laskin, Toledano, Geller), polyamines modulate cellular signaling (Thomas, Gallo), xenobiotics-induce alterations in transcription factors (Denhardt, Yurkow, Heck, Toledano), xenobiotics interact with DNA (Witz, Geller) and xenobiotics alter cell cycle control (Germino, Gallo). Highlights of research with specific chemicals include the findings that chromium is a potent activator of MAP kinase activity in rat hepatocytes (Yurkow), ozone treatment of rats stimulates the formation of pulmonary nitric oxide (D. Laskin and J. Laskin), the chemical photosensitizer psoralen inhibits epidermal growth factor receptor tyrosine kinase activity in skin cells (J. Laskin, Gallo) and the potent environmental toxin dioxin dozen regulates the estrogen receptor (Gallo) and stimulates nitric oxide production (Heck). This core members utilize the Enzymes and Antibodies, Molecular Genetics, Molecular Pathology, Chemical Analysis and Statistical Analysis Facility Cores. This core extensively uses the Analytical Cytometry/Image Analysis Facility Core which provides a broad range of expertise in modem techniques in cell biology. Using techniques in flow cytometry, fluorescence image analysis and confocal microscopy, multi parameter fluorescence analysis, cell sorting, cell cycle analysis, low level light imaging and three dimensional image reconstruction are performed.
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