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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Molecular mechanisms of androgen action

Awarded: NOK 6.2 mill.

Androgens are essential for a wide range of important biological processes. These include the development and maintenance of male reproductive organs, hair cycle and skeletal muscle, as well as regulation of lipid metabolism and bone remodelling. Androgen s are implicated in pathological processes, such as prostate cancer, spinal and bulbar muscular atrophy, and androgen-insensitivity syndrome. Androgen action is mediated by the androgen receptor (AR), a ligand-modulated transcription factor of the nuclear receptor superfamily. Although there has been a significant increase in our knowledge of how AR functions, its dynamic interactions with chromatin in living cells remain largely unexplored. In addition, there is limited information on the AR target gene s and their functional roles under normal or pathopysiological conditions. Furthermore, AR signalling is known to interact with other signalling pathways in the cell with important implications for which limited information is available. The goal of this research project is to uncover some of the molecular details of AR action. To that end, AR-chromatin interactions in living cells will be studied by a recently established unique cell culture system in our laboratory. Furthermore, functional characteriza tion of several AR target genes that have been cloned in our laboratory and implicated in prostate cancer and metabolic disease will be carried out. By better understanding of how AR functions, we will have a better understanding of how a simple hormone can give rise to such dramatic effects on a cell, under both normal and pathophysiological conditions. This information can then be potentially used in devising better diagnostic, prognostic, and therapeutic approaches for diseases such as prostate cancer and metabolic disease.

Funding scheme:

FRIMEDBIO-Fri prosj.st. med.,helse,biol

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