Functional Cancer Genomics

Group Leader

Theurillat Jean-Philippe, MD

Members

Bernasocchi Tiziano, PhD
Bolis Marco, PhD, Bioinformatics
Bossi Daniela, PhD
Ceserani Valentina, MSc, Technician
Costanzo Federico, PhD, Research Scientist
El Tekle Geniver, PhD
Formaggio Nicolò, PhD Student
Isenschmid Manuela, MSc, Technician
Theurillat Jean-Philippe, MD, Group Leader
Vallerga Arianna, 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.

References

 

  • Monika Oberhuber Matteo Pecoraro Mate Rusz Georg Oberhuber Maritta WieselbergPeter Haslinger Elisabeth Gurnhofer , Michaela Schlederer Tanja Limberger Sabine Lagger Jan Pencik Petra Kodajova Sandra Högler Georg Stockmaier Sandra Grund-Gröschke Fritz Aberger Marco Bolis Jean-Philippe Theurillat Robert Wiebringhaus Theresa Weiss Andrea Haitel Marc Brehme Wolfgang Wadsak Johannes Griss Thomas Mohr Alexandra Hofer ,  Anton Jäger Jürgen Pollheimer Gerda Egger Gunda Koellensperger Matthias Mann Brigitte HantuschLukas Kenner. STAT3-dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer.
  • Abdullah Alajati Mariantonietta D’Ambrosio Martina Troiani Simone Mosole Laura Pellegrini Jingjing Chen Ajinkya Revandkar Marco Bolis Jean-Philippe Theurillat Ilaria GucciniMarco LosaArianna CalcinottoGaston De BernardisEmiliano PasquiniRocco D’AntuonoAdam SharpInes FigueiredoDaniel Nava Rodrigues Jonathan WeltiVeronica GilWei YuanTatjana VlajnicLukas BubendorfGiovanna ChiorinoLetizia GnettiVerónica TorranoArkaitz CarracedoLaura CampleseSusumu HirabayashiElena CanatoGianfranco PasutMonica MontopoliJan Hendrik RüschoffPeter WildHolger MochJohann De BonoAndrea Alimonti.  CDCP1 overexpression drives prostate cancer progression and can be targeted in vivo. 2020 May 1;130(5):2435-2450 PMID: 32250342
  • Maria J Nabais SáGeniver El TekleArjan P M de BrouwerSarah L SawyerDaniela Del GaudioMichael J ParkerFarah KananiMarie-José H van den BoogaardKoen van GassenMargot I Van AllenKlaas WierengaGabriela PurcarinEllen Roy EliasAmber BegtrupJennifer Keller-RameyTiziano BernasocchiLaurens van de Wiel,  Christian GilissenHanka VenselaarRolph PfundtLisenka E L M VissersJean-Philippe P TheurillatBert B A de VriesDe Novo Variants in SPOP Cause Two Clinically Distinct Neurodevelopmental Disorders. 2020 Mar 5;106(3):405-411 PMID: 32109420
  • Karolina PietrzakRostyslav KuzyakivRonald SimonMarco BolisDominik BärRossana ApriglianoJean-Philippe TheurillatGuido SauterRaffaella Santoro. TIP5 primes prostate luminal cells for the oncogenic transformation mediated by PTEN-loss. 2020 Feb 18;117(7):3637-3647 PMID: 32024754
  • 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.
  • Anna C Groner, Laura CatoJonas de Tribolet-HardyTiziano BernasocchiHana JanouskovaDiana MelchersRené HoutmanAndrew C B CatoPatrick TschoppLei GuAndrea CorsinottiQing ZhongChristian FankhauserChristine FritzCédric Poyet, Ulrich WagnerTiannan GuoRuedi AebersoldLevi A GarrawayPeter J WildJean-Philippe TheurillatMyles BrownTRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer. 2016 Jun 13;29(6):846-858 PMID: 27238081
  • Jean-Philippe P TheurillatNamrata D UdeshiWesley J ErringtonTanya SvinkinaSylvan C BacaMarius PopPeter J WildMirjam BlattnerAnna C GronerMark A RubinHolger MochGilbert G PriveSteven A CarrLevi A Garrawa. Prostate cancer. Ubiquitylome analysis identifies dysregulation of effector substrates in SPOP-mutant prostate cancer. 2014 Oct 3;346(6205):85-89 PMID: 25278611

References