Research Program: Tumor Biology and Progression Research
Assistant Professor, Department of Laboratory Medicine and Pathology

dehm@umn.edu
612-625-1504—office
612-625-1520—lab
Preferred method of contact: e-mail

Dr. Dehm received his Ph.D. in Biochemistry in 2003 from the University of Saskatchewan, Canada. His graduate research, carried out at the Saskatchewan Cancer Agency under the mentorship of Dr. Keith Bonham, focused on transcriptional regulation of c-Src oncogene expression. Dr. Dehm subsequently pursued postdoctoral training at the Mayo Clinic in the laboratory of Dr. Donald Tindall, where he studied mechanisms of androgen receptor transcriptional activation and prostate cancer therapy resistance. His graduate and postdoctoral training were supported by awards from the National Science and Engineering Research Council of Canada (NSERC) and the National Cancer Institute of Canada (NCIC). Dr. Dehm joined the faculty of the Department of Laboratory Medicine and Pathology at the University of Minnesota in 2008.

Research Interests

Nuclear receptors, transcription, gene expression, prostate cancer.

Research in the Dehm laboratory focuses on the role of the androgen receptor (AR) in prostate cancer development and progression. The AR is a steroid hormone receptor transcription factor important for normal prostate function, as well as the growth of prostate cancer. Because of the central importance of the AR in prostate cancer, the mainstay treatment for relapsed or metastatic disease is androgen depletion. The primary limitation of androgen depletion is that prostate cancer will eventually develop therapy resistance and recur with a lethal androgen depletion-independent phenotype. A wealth of clinical and experimental evidence has demonstrated that the AR is aberrantly re-activated at this stage of the disease and therefore remains a viable therapeutic target. Our laboratory employs molecular, biochemical, cell biology, and genetic approaches to understand the mechanisms of AR transcriptional regulation in cell- and xenograft-based models of prostate cancer progression. We have identified alternative mechanisms of AR activation that are impervious to current modes of androgen depletion, and are studying whether these mechanisms of AR activation can be exploited to develop novel targeted therapies for advanced prostate cancer.

Selected Publications

Raclaw KA, Heemers HV, Kidd EM, Dehm SM, Tindall DJ. Induction of FLIP expression by androgens protects prostate cancer cells from TRAIL-mediated apoptosis. The Prostate, in press.

Dehm SM, Schmidt LJ, Heemers HV, Vessella RL, Tindall DJ. Splicing of a novel AR exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance. Cancer Res. 2008;68:5469-5477.

Heemers HV, Regan KM, Dehm SM, Tindall DJ. Androgen induction of the androgen receptor co-activator FHL2: evidence for a role for serum response factor in prostate cancer. Cancer Res. 2007;67:10592-10599.

Dehm SM, Regan KM, Schmidt, LJ, Tindall DJ. Selective role of an NH2-terminal WxxLF motif for aberrant androgen receptor activation in androgen depletion-independent prostate cancer cells. Cancer Res. 2007;67:10067-10077.

Dehm SM, Tindall DJ. Androgen receptor structural and functional elements: Role and regulation in prostate cancer. Mol Endocrinol. 2007;2:2855-2863.

Dehm SM, Tindall DJ. Ligand-independent androgen receptor activity is activation function-2-independent and resistant to antiandrogens in androgen refractory prostate cancer cells. J Biol Chem. 2006;28:27882-27893.

Dehm SM, Tindall DJ. Molecular regulation of androgen action in prostate cancer. J Cell Biochem. 2006;99:333-344.

Debes JD, Comuzzi B, Schmidt LJ, Dehm SM, Culig Z, Tindall DJ. p300 regulates androgen receptor-independent expression of prostate-specific antigen in prostate cancer cells treated chronically with interleukin-6. Cancer Res. 2005;65,5965-7593.

Dehm SM, Tindall DJ. Regulation of androgen receptor signaling in prostate cancer. Expert Rev Anticancer Ther. 2005;5:63-74.