Overview | Research projects | Group members | Collaborations | Selected Publications
Overview
Our research focuses on understanding how genetic diversity provides insights into the predisposition to cancer and how somatic genomic aberrations contribute to tumor progression. As we learn more about the complexity of the human genome from programs like the HapMap and ENCODE projects, it becomes evident that our understanding of genetic diversity is incomplete. Structural variants, specifically in the form of Copy Number Variants (CNVs), add to the genomic diversity encoded in single DNA base-pair difference (Single Nucleotide Polymorphism, SNPs) and may contribute to cancer susceptibility. Genetic diversity and somatic mutations provide cancer a selective advantage to develop and progress.
In a highly interdisciplinary and systems biology framework, our group contributes to the understanding of the genomic complexity that defines human tumors and of the involvement of inherited genetic make-up through the development and application of computational tools and in vitro experiments. Our group is currently working on Whole Genome and Whole Exome Sequencing data of prostate cancer in collaboration with Weill Cornell Medical College and the Broad Institute and Weill Cornell Medical College. Methodological work is dedicated to the assessment of tumor evolution through clonality and sub-clonality quantification.
See more details at (demichelislab.unitn.it). Post-doc positions are open (contact demichelis [at] science.unitn.it)
Research Projects
- Functional Validation of Prostate Cancer Driving Mutations (funded by The Department of Defense, USA, Synergy Award);
- Comprehensive Prostate Cancer Characterization by Genomic and Transcriptomic Profiling (funded by NIH);
- Recurrent genomic alterations as biomarkers predictive of the response to brachytherapy treatment in prostate cancer patients (funded by the Fondazione Trentina per la Ricerca sui Tumori);
- Defining Heritable Cancer Risk Variants in the Prostate (funded by AIRC);
- Towards Understanding the Genetic Predisposition for Signaling Pathway Activation in Aggressive Prostate Cancer;
- Identification and functional characterization of inherited CNVs at a single locus and at biological pathway level.
Group members
- Francesca Demichelis, PI
- Davide Prandi, postdoctoral fellow
- Alessandro Romanel, postdoctoral fellow
- Matteo Benelli, postdoctoral fellow
- Sonia Iolanda Garritano, postdoctoral fellow
- Chiara Cantaloni (joint APSS)
- Nicola A. Casiraghi, PhD student
- Blerta Stringa, PhD student
- Alessio Locallo, fellowship post bachelor degree
Collaborations
- Mark A Rubin, Weill Cornell Medical College, USA
- Levi Garraway, Dana-Farber Cancer Institute, USA
- Arul M. Chinnaiyan, University of Michigan, USA
- Mark B Gerstein, Yale University, USA
- Robert Klein, Memorial Sloan-Kettering Cancer Center, USA
- Dolores Di Vizio, Childrens Hospital, Harvard Medical School, USA
- Holger Sültmann, German Cancer Research Center (DKFZ), Germany
- Helmut Klocker, University Hospital Innsbruck, Austria
Selected publications (2011-2017)
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. https://www.ncbi.nlm.nih.gov/
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. https://www.ncbi.nlm.nih.gov/
Baca SC, Prandi D, Lawrence MS, Mosquera J-M, Romanel A, Drier Y, Park K, Kitabayashi N, MacDonald TY, Ghandi M, Van Allen E, Kryukov GV, Sboner A, Theurillat J-P, 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.
Poptsova M, Banerjee S, Gokcumen O, Rubin MA, Demichelis F. Impact of Constitutional Copy Number Variants on Biological Pathway Evolution. BMC Evol Biol. 2013 Jan 23;13:19.
Schaefer G*, Mosquera J-M*, Ramoner R, Park K, Romanel A, Steiner E, Horninger W, Bektic J, Ladurner-Rennau M, Rubin MA, Demichelis F*, Klocker H*. Distinct ERG rearrangement prevalence in prostate cancer - higher frequency in young age and in low PSA prostate cancer. Prostate Cancer Prostatic Dis advance online publication, February 5, 2013; doi:10.1038/pcan.2013.4
Demichelis F*, Setlur SR*, Banerjee S, Chakravarty D, Chen JYH, Chen CX, Huang J, Beltran H, Oldridge DA, Kitabayashi N, Stenzel B, Schaefer G, Horninger W, Bektic J, Chinnaiyan AM, Goldenberg S, Siddiqui J, Regan M, Kearney M, Soong TD, Rickman DS, Elemento O, Wei JT, Scherr DS, Sanda MA, Bartsch G, Lee C*, Klocker H*, Rubin MA*. Identification of functionally active, low frequency copy number variants at 15q21.3 and 12q21.31 associated with prostate cancer risk. Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6686-91.
Rickman DS, Soong TD, Moss B, Mosquera JM, Dlabal J, Terry S, MacDonald SY, Tripodi J, Bunting K, Najfeld V, Demichelis F, Melnick AM, Elemento O, Rubin MA. Oncogene-Mediated Alterations in Chromatin Conformation, Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):9083-8.
Barbieri CE*, Baca SC*, Lawrence MS*, Demichelis F, et al. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat Genet. 2012 May 20;44(6):685-9.
Beltran H, Rickman DS, Park K, Chae SS, Sboner A, MacDonald TY, Wang Y, Sheikh KL, Terry S, Tagawa ST, Dhir R, Nelson JB, de la Taille A, Allory Y, Gerstein MB, Perner S, Pienta KJ, Chinnaiyan AM, Wang Y, Collins CC, Gleave ME, Demichelis F, Nanus DM, Rubin MA. Molecular Characterization of Neuroendocrine Prostate Cancer and Identification of New Drug Targets. Cancer Discovery. 2011 Nov;1(6): 487-495.
Pflueger D, Terry S, Sboner A, Habegger L, Esgueva R, Lin P-C, Svensson MA, Kitabayashi N, Moss BJ, MacDonald TY, Cao X, Barrette T, Tewari AK, Chee MS, Chinnaiyan AM, Rickman DS, Demichelis F., Gerstein MB, Rubin MA. Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing. Genome Res. 2011 Jan;21(1):56-67.
Berger MF*, Lawrence MS*, Demichelis F*, Drier Y*, Cibulskis K, Sivachenko AY, Sboner A, Esgueva R, Pflueger D, Sougnez C, Onofrio R, Carter SL, Park K, Habegger L, Ambrogio L, Fennell T, Parkin M, Saksena G, Voet D, Ramos AH, Pugh TJ, Wilkinson J, Fisher S, Winckler W, Mahan S, Ardlie K, Baldwin J, Simons JW, Kitabayashi N, MacDonald TY, Kantoff PW, Chin L, Gabriel SB, Gerstein MB, Golub TR, Meyerson M, Tewari A, Lander ES, Getz G, Rubin MA*, Garraway LA*. The genomic complexity of primary human prostate cancer. Nature. 2011 Feb 10;470(7333):214-20.
Banerjee S, Oldridge D, Poptsova M, Hussain WM, Chakravarty D, Demichelis F. A computational framework discovers new copy number variants with functional importance. PLoS One. 2011 Mar 29;6(3):e17539.