Functional Cancer Genomics

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Members

Anna Rinaldi, PhD
Geniver El Tekle, PhD student
Jean-Philippe Theurillat, MD Group Leader
Marco Bolis, Bioinformatics
Oliver Achermann, M.Sc. student
Tiziano Bernasocchi, PhD student

Overview

Cancer is driven by cardinal genetic alterations that activate driver genes. Driver mutations are not only essential to initiate tumorigenesis, but are also required for tumor growth and maintenance. This raises the possibility to target these mutations, opening more specific, therapeutic opportunities to treat cancer patients.

Our research group focuses on new drivers of prostate cancer with emphasis on advanced, castration-resistant disease. We aim to explore the roles of these genes in tumorigenesis with the ultimate goal to develop new therapeutic avenues for patients suffering from prostate cancer (exemplified in Fig. 1).

Fig. 1. TRIM24 is a druggable co-activator of the androgen receptor (AR) and a driver of castration-resistant prostate cancer (see also PMID: 27238081).

In addition, our group develops new strategies to empirically tailor cancer therapy in the clinic. Patient-derived tumor cells will be used to test drug responses prior treating the patient. This approach may guide decision-making in the clinic in an individualized manner (Fig. 2).

jpt-fig2

Fig. 2. Patient-derived cancer and normal cell lines may allow empirical testing of drug responses in culture prior treating the patient.

Current projects

  • Functional characterization of new prostate cancer drivers implicated in chromatin remodeling and protein ubiquitylation
  • Engineering of small molecules against prostate cancer targets
  • Generation and engineering of patient-derived cell line models

Our group is committed to train the future generation of cancer researcher. Master thesis applications are welcome at any time and we will support you with scholarships.

In press

  • Janouskova H, El Tekle G, Bellini E, Udeshi ND, Rinaldi A, Ulbricht A, Bernasocchi T, Civenni G, Losa M, Svinkina T, Bielski CM, Kryukov GV, Cascione L, Napoli S, Enchev RI, Mutch DG, Carney ME, Berchuck A, Winterhoff BJN, Broaddus RR, Schraml P, Moch H, Bertoni F, Catapano CV, Peter M, Carr SA, Garraway LA, Wild PJ, Theurillat JP. Opposing effects of cancer type-specific SPOP mutations on BET protein degradation and sensitivity to BET inhibitors. Accepted for publication Nat Med Jun 2017.

References

  • Groner AC1, Cato L1, de Tribolet-Hardy J1, Bernasocchi T2, Janouskova H2, Melchers D3, Houtman R3, Cato AC4, Tschopp P5, Gu L6, Corsinotti A7, Zhong Q8, Fankhauser C9, Fritz C8, Poyet C10, Wagner U8, Guo T11, Aebersold R12, Garraway LA13, Wild PJ8, Theurillat JP14, Brown M15. TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer. Cancer Cell. 2016 Jun 13;29(6):846-58. PMID: 27238081.

  • Theurillat JP#1,2,3, Udeshi ND#1, Errington WJ#4,5, Svinkina T1, Baca SC2,3, Pop M1,2,3, Wild PJ6, Blattner M7, Groner AC3, Rubin MA7,8, Moch H6, Prive GG4,5, Carr SA1, Garraway LA1,2,3,9. Prostate cancer. Ubiquitylome analysis identifies dysregulation of effector substrates in SPOP-mutant prostate cancer. Science. 2014 Oct 3;346(6205):85-89. PMID: 25278611.

  • Baca SC1, Prandi D, Lawrence MS, Mosquera JM, Romanel A, Drier Y, Park K, Kitabayashi N, MacDonald TY, Ghandi M, Van Allen E, Kryukov GV, Sboner A, Theurillat JP, Soong TD, Nickerson E, Auclair D, Tewari A, Beltran H, Onofrio RC, Boysen G, Guiducci C, Barbieri CE, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Ramos AH, Winckler W, Cipicchio M, Ardlie K, Kantoff PW, Berger MF, Gabriel SB, Golub TR, Meyerson M, Lander ES, Elemento O, Getz G, Demichelis F, Rubin MA, Garraway LA. Punctuated evolution of prostate cancer genomes. Cell. 2013 Apr 25;153(3):666-77. PMID: 23622249.

  • Whittaker SR1, Theurillat JP, Van Allen E, Wagle N, Hsiao J, Cowley GS, Schadendorf D, Root DE, Garraway LA. A genome-scale RNA interference screen implicates NF1 loss in resistance to RAF inhibition. Cancer Discov. 2013 Mar;3(3):350-62. PMID: 23288408.

  • Barbieri CE1, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat JP, White TA, Stojanov P, Van Allen E, Stransky N, Nickerson E, Chae SS, Boysen G, Auclair D, Onofrio RC, Park K, Kitabayashi N, MacDonald TY, Sheikh K, Vuong T, Guiducci C, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Hussain WM, Ramos AH, Winckler W, Redman MC, Ardlie K, Tewari AK, Mosquera JM, Rupp N, Wild PJ, Moch H, Morrissey C, Nelson PS, Kantoff PW, Gabriel SB, Golub TR, Meyerson M, Lander ES, Getz G, Rubin MA, Garraway LA. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat Genet. 2012 May 20;44(6):685-9. PMID: 22610119.

  • Theurillat JP1, Metzler SC, Henzi N, Djouder N, Helbling M, Zimmermann AK, Jacob F, Soltermann A, Caduff R, Heinzelmann-Schwarz V, Moch H, Krek W. URI is an oncogene amplified in ovarian cancer cells and is required for their survival. Cancer Cell. 2011 Mar 8;19(3):317-32. PMID: 21397856.