Bryce M. Paschal, PhD, University of Virginia

The Paschal laboratory studies how nuclear transport and signal transduction control the compartmentalization and activity of transcription factors, particularly in the context of prostate cancer. A major focus of these studies is the androgen receptor (AR), a steroid hormone receptor that is critical for prostate cell growth. Translocation of AR through the nuclear pore complex (NPC) relies on features common to most nuclear transport pathways: (i) the use of nuclear import or export signals; (ii) the recognition of these signals by receptors that mediate translocation through the NPC; and (iii) RanGTPase-dependent assembly and disassembly of transport complexes. The signals that specify nuclear import and export of AR, the receptors that mediate AR translocation, and the role of the RanGTPase in AR transport are all under investigation in my laboratory. Nuclear export would be expected to provide an effective mechanism for terminating the transcriptional response to androgen, however, we have recently found that AR translocation to the cytoplasm is important for its activity in the nucleus. This apparent paradox may reflect an undefined step in AR maturation, or crosstalk between AR and signal transduction pathways in the cytoplasm.

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