Overview

Our research focuses on understanding how genetic diversity and genomic aberrations contribute to tumor evolution and progression. The final goal is to advance the field of Precision Oncology by identifying biomarkers to predict progression, to select pharmacological treatment and to monitor cancer patients’ treatment response, through the integration of tissue and liquid biopsy-based studies. The laboratory integrates large-scale experimental and computational work with main focus on GU cancers and is involved in international collaborative studies on prostate cancer.
Laboratory website demichelislab.eu The SPICE project

Research Projects

  • To short list synthetic lethal combinations via pan-cancer ad hoc computational analyses of thousands of human sequenced tumors, followed by in vitro validation and characterization of relevant hits (funded by ERC, MIUR, FTRT);

  • To identify the molecular features involved in the trans-differentiation of prostate cancer adenocarcinoma to AR indifferent phenotype, including to neuroendocrine phenotype (funded by NIH, PCF);

  • To study the effect of inherited variants within transcriptionally active regions and chromatin regulators on molecularly defined prostate cancer sub-classes (funded by AIRC);

  • To study the effect of somatic alterations and inherited variants in DNA repair genes on prostate cancer aggressiveness (funded by MIUR, FTRT);

  • To develop multi-analyte liquid biopsies tools spanning cell-free DNA genomics and methylation, and circulating extra-cellular vesicles for translational and clinical research in prostate and breast cancers (funded by NIH, PCF, CRUK-AIRC-Accelerator Award, Fondazione Caritro).

Group members

  • Francesca Demichelis, PI
  • Riccardo Bevilacqua, PhD student (exp.)
  • Thomas Cantore, PhD student (comp.)
  • Yari Ciani, post-doc (comp.)
  • Giacomo D’Amato, research fellow (comp.)
  • Giulia Fracassi, PhD student (exp.)
  • Gian Marco Franceschini, PhD student (comp.)
  • Paola Gasperini, post-doc (exp.)
  • Francesca Lorenzin, post-doc (exp.)
  • Angela Martinelli, research fellow (exp.)
  • Vera Mugoni, post-doc (exp.)
  • Caterina Nardella, program manager
  • Francesco Orlando, PhD student (comp.)
  • Marta Paoli, PhD student (comp.)
  • Orsetta Quaini, research fellow (exp.)
  • Simone Tomasini, research fellow (exp.)
  • Federico Vannuccini, PhD student (comp.)
  • Alessia Villani, research fellow (exp.)

Open positions are available, please contact: f.demichelis@unitn.it

Collaborations

  • Gert Attard, UCL, London
  • Himisha Beltran, DFCI, Boston
  • Matteo Benelli, Prato, Italy
  • Dolores Di Vizio, Cedars-Sinai, Los Angeles
  • ​Olivier Elemento, Weill Cornell Medicine, New York
  • Bishoy Faltas, Weill Cornell Medicine, New York
  • Helmut Klocker, University Hospital Innsbruck, Innsbruck
  • Mark A Rubin, University of Bern, Bern

Funding

Bando: PRIN 2022 (D.D. 104/22)
LIFT: LIquid biopsy and Functional imaging for hormone sensitive prosTate cancer patients
Francesca Demichelis, coordinatrice
Codice Protocollo: 2022Y9NP8K    CUP: E53D23013200006

Selected publications (2011-2017)

Ciani Y, Fedrizzi T, Prandi D, Lorenzin F, Locallo A, Gasperini P, Franceschini GM, Benelli M, Elemento O, Fava LL, Inga A, Demichelis F. Allele-specific genomic data elucidate the role of somatic gain and copy-number neutral loss of heterozygosity in cancer. Cell Syst. 2021 Oct 26:S2405-4712(21)00383-5. doi: 10.1016/j.cels.2021.10.001.

Benelli M, Franceschini GM, Magi A, Romagnoli D, Biagioni C, Migliaccio I, Malorni L, Demichelis F. Charting differentially methylated regions in cancer with Rocker-meth. Commun Biol. 2021 Nov 2;4(1):1249. doi: 10.1038/s42003-021-02761-3.

Wu A, Cremaschi P, Wetterskog D, Conteduca V, Franceschini GM, Kleftogiannis D, Jayaram A, Sandhu S, Wong SQ, Benelli M, Salvi S, Gurioli G, Feber A, Pereira MB, Wingate AM, Gonzalez-Billalebeitia E, De Giorgi U, Demichelis F., Lise S, Attard G. Genome-wide plasma DNA methylation features of metastatic prostate cancer. J Clin Invest. 2020 Apr 1;130(4):1991-2000. doi: 10.1172/JCI130887.

Beltran H, Romanel A, Conteduca V, Casiraghi N, Sigouros M, Franceschini GM, Orlando F, Fedrizzi T, Ku SY, Dann E, Alonso A, Mosquera JM, Sboner A, Xiang J, Elemento O, Nanus DM, Tagawa ST, Benelli M, Demichelis F. Circulating tumor DNA profile recognizes transformation to castration-resistant neuroendocrine prostate cancer. J Clin Invest. 2020 Apr 1;130(4):1653-1668. doi: 10.1172/JCI131041.

Persi E, Prandi D, Wolf YI, Pozniak Y, Barnabas GD, Levanon K, Barshack I, Barbieri C, Gasperini P, Beltran H, Faltas BM, Rubin MA, Geiger T, Koonin EV, Demichelis F., Horn D. Proteomic and genomic signatures of repeat instability in cancer and adjacent normal tissues. Proc Natl Acad Sci U S A. 2019 Aug 20;116(34):16987-16996. doi: 10.1073/pnas.1908790116. Epub 2019 Aug 6.

Abida W, Cyrta J, Heller G, Prandi D, Armenia J, Coleman I, Cieslik M, Benelli M, Robinson D, Van Allen EM, Sboner A, Fedrizzi T, Mosquera JM, Robinson BD, De Sarkar N, Kunju LP, Tomlins S, Wu YM, Nava Rodrigues D, Loda M, Gopalan A, Reuter VE, Pritchard CC, Mateo J, Bianchini D, Miranda S, Carreira S, Rescigno P, Filipenko J, Vinson J, Montgomery RB, Beltran H, Heath EI, Scher HI, Kantoff PW, Taplin ME, Schultz N, deBono JS, Demichelis F., Nelson PS, Rubin MA, Chinnaiyan AM, Sawyers CL. Genomic correlates of clinical outcome in advanced prostate cancer. Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11428-11436. doi: 10.1073/pnas.1902651116. Epub 2019 May 6.

Mu P, Zhang Z, Benelli M, Karthaus WR, Hoover E, Chen C-C, Wongvipat J, Ku S-Y, Gao D, Cao Z, Shah N, Adams EJ, Abida W, Watson PA, Prandi D, Huang C-H, de Stanchina E, Lowe SW, Ellis L, Beltran H, Rubin MA, Goodrich DW, Demichelis F., Sawyers CL. SOX2 promotes lineage plasticity and antiandrogen resistance in TP53 and RB1 deficient prostate cancer. Science. 2017 Jan 6;355(6320):84-88.

Romanel A, Garritano S, Stringa B, Blattner M, Dalfovo D, Chakravarty D, Cotter KA, Petris G, Dhingra P, Gasperini P, Cereseto A, Elemento O, Sboner A, Khurana E, Inga A, Rubin MA, Demichelis F. Inherited determinants of early recurrent somatic mutations in prostate cancer. Nat Commun. 2017 Jun 29;8(1):48.

Rubin MA, Girelli G, Demichelis F. Genomic Correlates to the newly proposed Grading Prognostic Groups for Prostate Cancer. Eur Urol. 2016 Apr;69(4):557-60.

Beltran H &, Prandi D, Mosquera JM, Benelli M, Puca L, Cyrta J, Marotz C, Giannopoulou E, Chakravarthi BV, Varambally S, Tomlins SA, Nanus DM, Tagawa ST, Van Allen EM, Elemento O, Sboner A, Garraway L., Rubin MA., Demichelis F. Divergent clonal evolution of androgen receptor indifferent castration resistant prostate cancer. Nat Med. 2016 Mar;22(3):298-305.

Faltas BM, Prandi D, Tagawa ST, Molina AM, Nanus DM, Sternberg C, Rosenberg J, Mosquera J-M, Robinson B, Elemento O, Sboner A, Beltran H., Demichelis F., Rubin MA.. Clonal Evolution of Chemotherapy-resistant Urothelial Carcinoma. Nat Genet. 2016 Dec;48(12):1490-1499.

Mugoni V, Ciani Y, Nardella C, Demichelis F. Circulating RNAs in prostate cancer patients. Cancer Lett. 2022 Jan 1;524:57-69. doi: 10.1016/j.canlet.2021.10.011. Epub 2021 Oct 14. Review

Beltran H, Demichelis F. Therapy considerations in neuroendocrine prostate cancer: what next?
Endocr Relat Cancer. 2021 Jul 15;28(8):T67-T78. doi: 10.1530/ERC-21-0140. Review

Persi E, Wolf YI, Horn D, Ruppin E, Demichelis F, Gatenby RA, Gillies RJ, Koonin EV. Mutation-selection balance and compensatory mechanisms in tumour evolution. Nat Rev Genet. 2021 Apr;22(4):251-262. Review