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Molecular Carcinogenesis and Toxicology
The long term goals of the Molecular Toxicology & Carcinogenesis Division are to elucidate the mechanisms of environmental agents that exert adverse effects on human health and to provide molecular rationales for the development of effective strategies for cancer prevention and intervention. Major focuses of the Division are to understand the genetic and epigenetic changes elicited by environmental exposure including life styles and ageing process by a combination of biochemical, molecular and genetic approaches. Molecular carcinogenesis is a complex process in which the interactions between genetics and environmental factors result in a condition that is more or less favorable for transformation and the subsequent development and progression of cancer. It is well known that a major proportion of human cancers are attributable to environmental factors and to genetic susceptibility to those factors. Therefore, it is imperative to gain a better understanding of the cellular and molecular mechanisms underlying the environmental origins of malignant transformation, as well as genetic and epigenetic factors affecting susceptibility of individuals to environmental toxicants or carcinogens.
The Molecular Toxicology & Carcinogenesis Division is comprised of independent research laboratories with principal investigators who have strong expertise in biochemistry, cell biology, molecular biology, immunology, and/or oncology. Scientists in the Division is actively engaged in studying in the following areas of research including cell signaling and DNA damage & repair in response to environmental exposure, chromatin structures and epigenetics on gene expression, and mechanisms suppressing genomic instability, and molecular mode of actions that control cell division and cell death. The Division is particularly strong in metal carcinogenesis studies with an emphasis on inorganic compounds, such as arsenic, nickel, chromium and cadmium. The molecular toxicological effects of these metals and other agents are studied by examining their functional interactions with DNA and gene products. The biochemistry of metal-mediated active oxygen species and the biological consequences that result from such reactive radicals is of great interest to many members of this Division. Chronic and acute exposure to metal toxicants and other environmental factors interferes with the normal control mechanisms that regulate the levels of tissue-specific receptors, signal transducers and effector molecules. Thus, a major focus is on the identification of critical molecular circuits that are switched on/off by the exposure to a particular environmental agent, resulting in the modulation in cell proliferation and/or differentiation. Given that components of the cellular machinery that respond to the environmental factors are not only genetically determined but are also greatly influenced by the epigenetic mechanisms, several scientists of the Division also attempt to understand the mode of actions of many metal toxicants on the modification of chromatic structures, as well as other epigenetic factors, that cause individual variations in susceptibility or resistance to particular environmental agents.
Scientists in the Division use a wide range of contemporary cellular and molecular approaches to elucidate the mechanisms that suppress genomic instability and tumorigenesis in normal cells. Methodologies include genomics including ChIP on Chip, DNA-Seq and RNA-Seq, proteomics, bioinformatics, and transgenic and recombinant inbred rodent models, as well as routine cellular and molecular biological approaches.