The long range objective of the laboratory is to understand the cellular and molecular mechanisms by which signaling pathways and downstream transcription factors coordinate the specification of adrenocortical cells within the adrenal gland. Recent work emphasizes the dysregulated growth of…
more adrenocortical subcapsular stem/progenitor cells in development and cancer. SF-1 is a nuclear receptor that defines the adrenocortical cell and is required for transcriptional programs that regulate both proliferation and differentiation of the gland. The laboratory studies the mitogenic signals that initiate assembly of the SF-1 transcription complex using a combination of biochemical technologies such as ChIP-chip and in vivo work with genetically engineered mice. The role of Wnt ligands in adrenocortical stem/progenitor cell biology and how dysregulated Wnt signaling through beta-catenin contributes to adrenocortical carcinoma in mice and humans has become a burgeoning area of interest. Recent studies reveal that two novel Wnt target genes, Dax-1 and inhibin regulate the multipotency and adrenal-specific differentiation of these cells. Genetic approaches including positional cloning and candidate gene screening have characterized novel genes that direct the adrenal developmental program and contribute to the development of cancer. They have recently cloned the gene responsible for adrenocortical dysplasia (Acd). Acd is a novel telomere binding protein. This has led to an interest in the role of telomere maintenance in adrenocortical stem cell renewal and the development of adrenocortical carcinoma.
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