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B.S., University of Minnesota, Minneapolis, MN, 2009
In the United States, one in seven men will be diagnosed with prostate cancer. Prostate cancer is an androgen-dependent disease, and androgen function is controlled by the androgen receptor (AR), a hormone activated transcription factor. Treatments targeting AR are highly effective at inhibiting disease progression. However, therapeutic resistance and emergence of castration resistant prostate cancer is responsible for virtually all prostate cancer mortality. Constitutively active AR splice variants have been implicated as drivers of castration resistant prostate cancer. AR variants consist of the unstructured AR NH2-terminal domain (NTD) and the AR DNA binding domain, but lack the ligand binding domain (LBD), which is targeted by current therapies. While our understanding of proteins that regulate the AR LBD is well developed, there is less known about the regulation of the NTD. This represents a significant gap in knowledge given that the AR NTD is the transcriptional “engine” of the AR and AR variants. To address this, the Dehm Lab used a new technique called RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins) with a pair of isogenic prostate cancer cell lines that express either full-length AR or variant AR. This approach identified a cohort of proteins that interact with and are likely to regulate activity of the AR NTD. The identification of unknown AR regulators signifies a high potential for discovery related to AR function in castration resistant prostate cancer. Using molecular methods and bioinformatics tools, the objective of my research is to identify and characterize unknown AR regulators and their potential roles in prostate cancer development and progression.
Daniel M. and S.M. Dehm. 2016. Lessons from tissue compartment-specific analysis of androgen receptor alterations in prostate cancer. J Steroid Biochem Mol Biol. In press