Scott Dehm, PhD

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

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

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

Graduate Programs Advising Statement


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

Daniel M, Knutson TP, Sperger JM, Li Y, Singh A, Stahlfeld CN, Passow C, Auch B, Lang JM, Dehm SM. AR gene rearrangement analysis in liquid biopsies reveals heterogeneity in lethal prostate cancer. Endocr Relat Cancer. 2021 Aug 11;28(9):645-655. doi: 10.1530/ERC-21-0157.

Li Y, Yang, R, Henzler C, Ho Y, Passow C, Auch B, Carreira S, Rodrigues DN, Bertan C, Hwang TH, Quigley DA, Dang HX, Morrissey C, Fraser M, Plymate SR, Maher CA, Feng FY, De Bono J, Dehm SM. Diverse AR Gene Rearrangements Mediate Resistance to Androgen Receptor Inhibitors in Metastatic Prostate Cancer. Clin. Cancer Res., 26(8):1965-1976, 2020.

Yang R, Van Etten JL, and Dehm SM. Indel detection from DNA and RNA sequencing data with transIndel. BMC Genomics, 201819(1):270. doi: 10.1186/s12864-018-4671-4..

Zadra G, Ribeiro CF, Chetta P, Ho Y, Cacciatore S, Gao X, Syamala S, Bango C, Photopoulos C, Huang Y, Tyekucheva S, Bastos DC, Tchaicha J, Lawney B, Uo T, D'Anello L, Csibi A, Kalekar R, Larimer B, Ellis L, Butler LM, Morrissey C, McGovern K, Palombella VJ, Kutok JL, Mahmood U, Bosari S, Adams J, Peluso S, Dehm SM, Plymate SR, Loda M. Inhibition of de-novo lipogenesis targets androgen receptor signaling in castration resistant prostate cancer. Proc. Natl. Acad. Sci. USA. 116: 631-640, 2019.

Quigley DA, Dang HX, Zhao SG, Lloyd P, Aggarwal R, Alumkal JJ, Foye A, Kothari V, Perry MD, Bailey AM, Playdle D, Barnard TJ, Zhang L, Zhang J, Youngren JF, Cieslik MP, Parolia A, Beer TM, Thomas G, Chi KN, Gleave M, Lack NA, Zoubeidi A, Reiter RE, Rettig MB, Witte O, Ryan CJ, Fong L, Kim W, Friedlander T, Chou J, Li H, Das R, Li H, Moussavi-Baygi R, Goodarzi H, Gilbert LA, Lara PN Jr, Evans CP, Goldstein TC, Stuart JM, Tomlins SA, Spratt DE, Cheetham RK, Cheng DT, Farh K, Gehring JS, Hakenberg J, Liao A, Febbo PG, Shon J, Sickler B, Batzoglou S, Knudsen KE, He HH, Huang J, Wyatt AW, Dehm SM, Ashworth A, Chinnaiyan AM, Maher CA, Small EJ, Feng FY. Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. Cell, 174:758-769, 2018

Viswanathan SR, Ha G, Hoff AM, Wala JA, Carrot-Zhang J, Whelan CW, Haradhvala NJ, Freeman SS, Reed SC, Rhoades J, Polak P, Cipicchio M, Wankowicz SA, Wong A, Kamath T, Zhang Z, Gydush GJ, Rotem D; PCF/SU2C International Prostate Cancer Dream Team, Love JC, Getz G, Gabriel S, Zhang CZ, Dehm SM, Nelson PS, Van Allen EM, Choudhury AD, Adalsteinsson VA, Beroukhim R, Taplin ME, Meyerson M. Structural alterations driving castration-resistant prostate cancer revealed by linked-read genome sequencing. Cell, 174: 433-447, 2018.

Kohli M, Ho Y, Hillman DW, Van Etten JL, Henzler C, Yang R, Sperger JM, Li Y, Tseng E, Hon T, Clark T, Tan W, Carlson RE, Wang L, Sicotte H, Thai H, Jimenez R, Huang H, Vedell PT, Eckloff BW, Quevedo JF, Pitot HC, Costello BA, Jen J, Wieben ED, Silverstein KAT, Lang JM, Wang L, Dehm SM. Androgen receptor variant AR-V9 is co-expressed with AR-V7 in prostate cancer metastases and predicts abiraterone resistance. Clin. Cancer Res., 23:4704-4715, 2017.

Van Etten J, Nyquist M, Li Y, Yang R, Ho Y, Johnson R, Ondigi O, Voytas DF, Henzler C, Dehm SM. Targeting a single alternative polyadenylation site to coordinately block expression of androgen receptor mRNA splice variants in prostate cancer. Cancer Res., 77(19):5228-5235, 2017

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. Nature Communications, 7:13668, 2016

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