Scott Dehm, PhD

Associate Professor and Apogee Enterprises Chair in Cancer Research, Department of Laboratory Medicine and Pathology

Scott Dehm

Contact Info

Office Phone 612-625-1504

Fax 612-626-4842

Lab Phone 612-625-1520

Mailing Address:
MMC 806 Mayo
420 Delaware
Minneapolis, MN 55455

Associate Professor and Apogee Enterprises Chair in Cancer Research, Department of Laboratory Medicine and Pathology

Associate Professor, Microbiology, Immunology and Cancer Biology (MICaB) Ph.D. Graduate Program

PhD, University of Saskatchewan, Canada (Biochemistry), 2003

BSc, University of Saskatchewan, Canada (Biochemistry), 1998


Awards & Recognition

  • Apogee Enterprises Chair in Cancer Research 2015 - Present
  • University of Minnesota Medical School Young Investigator Award, 2014
  • American Cancer Society Research Scholar, 2012
  • Department of Defense Prostate Cancer Research Program New Investigator, 2010
  • Prostate Cancer Foundation Young Investigator, 2008
  • National Cancer Institute of Canada/Terry Fox Foundation Post-Ph.D. Fellowship, 2004-2007
  • Natural Sciences and Engineering Research Council (NSERC) of Canada Ph.D. Studentship,
  • Most Distinguished Graduate, Department of Biochemistry, University of Saskatchewan,
    Canada, 1998
  • Merit Award, Society of Chemical Industry, Canadian Section, 1998
  • Biochemistry Award, Chemical Institute of Canada, 1997

Professional Associations

  • American Association for Cancer Research (AACR)
  • The Endocrine Society
  • Society for Basic Urologic Research (SBUR)
  • American Cancer Society Tumor Biochemistry and Endocrinology Review Panel, 2013-2016
  • Editorial Board, Hormones and Cancer, 2015-present
  • Editorial Board, Endocrine-Related Cancer, 2013-present
  • Associate Editor, BMC Cancer, 2012-present
  • NIH Tumor Cell Biology (TCB) Study Section Member, 2016-2020


Research Summary/Interests

Dr. Dehm is a member of the Division of Molecular Pathology and Genomics.  His research laboratory focuses on the role of the androgen receptor (AR) and alterations in AR signaling in prostate cancer development and progression. As they develop, nearly all metastatic prostate cancers remain dependent on androgens--male hormones of which testosterone is best known. Following treatment targeting the AR including anti-androgen drug therapies and surgical castration to prevent androgen production, patients typically develop resistance. Dehm studies the changes that occur in the AR in response to these drug therapies to understand the mechanisms underlying the progression to therapy-resistant disease. His work has revealed new ways in which cancer cells can re-activate the androgen/AR pathway. If these mechanisms are better understood, new AR-targeted therapies could be developed that suppress prostate cancer growth more effectively with more durable remissions.

Dr. Dehm’s research team employs a variety of genomic engineering, molecular biology, and biochemistry tools to home in on the regulatory behavior of the AR and the signals it uses to promote resistance. These tools are used to analyze clinical tissues, prostate cancer cell lines, models in which patient-derived tumor tissue is grown in mice (xenografts), and fresh surgical tissue that is propagated in the laboratory as explants. Dehm and his colleagues have found that altered protein forms of the AR, termed AR variants, can be synthesized in resistant tumors. These AR variants are missing the site of the protein responsible for binding to androgens, which is the same site to which anti-androgens bind. However, these AR variants retain all other parts of the protein that are required for binding to DNA and activation of transcription. Therefore, these AR variants are able to carry out most of the functions of the AR protein, but in a way that no longer require androgens and is completely insensitive to anti-androgens. Dehm and his co-investigators are now focused on understanding how these AR variants are regulated, with the ultimate goal of finding ways to inhibit them.

Transcription factors like AR variants are challenging drug targets because key binding events occur via protein:DNA or protein:protein interfaces rather than through the lock-and-key mechanism of androgen binding to the AR, which medicinal chemists can more readily exploit. However, Dehm notes that recent advances in small-molecule design and peptide chemistry have overcome some of these challenges, and could potentially be applied to AR variants. Ultimately, identifying and targeting key processes required for AR variants to remain active in prostate cancer cells could provide an avenue to overcome the challenge of therapeutic resistance in patients.


PubMed publications

  • Henzler C, Li Y, Yang R, McBride T, Ho Y, Sprenger C, Liu G, Coleman I, Lakely B, Li R, Ma S, Landman SR, Kumar V, Hwang TH, Raj GV, Higano CS, Morrissey C, Nelson PS, Plymate SR, Dehm SM.  Truncation and constitutive activation of the androgen receptor by diverse genomic rearrangements in prostate cancer.  Nat Commun. 2016 Nov 29;7:13668. doi: 10.1038/ncomms13668.
  • Chan SC, Selth LA, Li Y, Nyquist MD, Miao L, Bradner JE, Raj GV, Tilley WD, Dehm SM. Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies. Nucleic Acids Research, 43:5880-97, 2015. PMID: 25908785
  • Chan SC and Dehm SM. 2014. Constitutive activity of the androgen receptor. Advances in Pharmacology, 70:327-66.
  • Ware KE, Garcia-Blanco MA, Armstrong AJ, Dehm SM. 2014. Biologic and Clinical Significance of Androgen Receptor Variants in Castration Resistant Prostate Cancer. Endocrine Related Cancer, 21:T87-T103.
  • Dehm SM. 2013. Alternatively spliced protein variants: exploiting modularity to outwit cancer therapy. Cancer Research, 73:5309-14.
  • Li, Yingming; Chan, Siuchiu; Brand, Lucas J.; Hwang, TaeHyun; Silverstein, Kevin At T; Dehm, Scott M. Androgen receptor splice variants mediate enzalutamide resistance in castration-resistant prostate cancer cell lines. Cancer Research 2013 Jan 15:73(2) 483-9. Epub 2012 Nov 1. PMID 23117885
  • Nyquist MD, Li Y, Hwang TH, Manlove LS, Vessella RL, Silverstein KA, Voytas DF, Dehm SM. TALEN-Engineered AR gene rearrangements reveal endocrine uncoupling of androgen receptor in prostate cancer. Pro Natl Acad Sci USA 2013 Oct 22; 110 (43):17492-7. Epub2013 Oct 7. PMID 24101480
  • Brand LJ, Olson ME, Ravindranathan P, Guo H, Kempema AM, Andrews TE, Chen X, Raj GV, Harki DA, Dehm SM. EPI-001 is a selective peroxisome proliferator-activated receptor-gamma modulator with inhibitory effects on androgen receptor expression and activity in prostate cancer. Oncotarget 2015 Feb 28;6(6):3811-24. PMID 25669987
  • Chan SC, Li Y, Dehm SM. 2012. Androgen receptor splice variants activate AR target genes and support aberrant prostate cancer cell growth independent of the canonical AR nuclear localization signal. J. Biol. Chem., 287:19736-49.
  • Li Y, Hwang TH, Oseth LA, Hauge A, Vessella RL, Schmechel SC, Hirsch B, Beckman KB, Silverstein KA, Dehm SM. 2012. AR intragenic deletions linked to androgen receptor splice variant expression and activity in models of prostate cancer progression. Oncogene, 31:4759-67.
  • Li Y, Alsagabi M, Fan D, Bova GS, Tewfik AH, Dehm SM. 2011. Intragenic rearrangement and altered RNA splicing of the androgen receptor in a cell-based model of prostate cancer progression. Cancer Res. Mar 15;71(6):2108-17.