Current Research


The coordination of cell proliferation and differentiation during development, and in response to a changing environment, requires extensive communication between cells. To gain insight into how failure to appropriately coordinate these processes leads to abnormal or diseased states, it is necessary to understand the mechanisms by which transcription factors enter and exit the cell nucleus, in response to extracellular signals. Nuclear receptors, such as the thyroid hormone receptor (TR), are transcription factors that directly transduce extracellular signals, resulting in altered gene activity. Numerous studies have indicated that transcriptional silencing mediated by nuclear receptors is important in differentiation and development; for example, aberrant TR variants are associated with a variety of endocrine and neoplastic diseases. Research in my lab investigates molecular mechanisms regulating nuclear localization of TR variants; including v-ErbA, the product of a viral oncogene. v-ErbA is a mutated version of TR which does not respond to thyroid hormone and interferes with the actions of TR. Factors regulating subcellular localization are being characterized by analysis of the trafficking of native and green fluorescent protein (GFP)-tagged receptors in mammalian cells. Elucidation of differences in the way in which TR and variants interact with components of the nuclear transport machinery will aid in understanding the complex pattern of regulation of the cellular response to thyroid hormone, and how misregulation of traffic control may lead to cancer and endocrine disorders.

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