F Demichelis received her PhD in February 2005 from the International PhD School on Information and Communication Technology in Trento (Italy) where she developed systematic approaches to processing and understanding data generated through Tissue Microarray Technology (modelling heterogeneity/uncertainty in classification approaches relevant to biological entities such as intra-tumor protein expression). Between 2005-2007 she worked at the Brigham and Women's Hospital (Harvard Medical School), as computational biology Post-doc fellow. In joint projects with members of research groups at the Dana Farber Cancer Institute and the Broad Institute of MIT and Harvard, she developed analytical approaches for the analysis of cancer genomics datasets related to prostate cancer disease progression as part of a multi-institutional effort. Between 2008-20011, she worked at Weill Cornell Medical College as Assistant Professor in Pathology and Laboratory Medicine and at the Institute for Computational Biomedicine. Her group focused on the study of structural variants (copy number variations - CNVs) as risk factors for cancer development and as potential facilitators (“triggers”) for specific somatic alterations (funded by DOD Young Investigator Award). From 2008 to 2010, she served as co-chair of the analysis team for Copy Number Variations in genome-wide association studies MicroArray Quality Control (MAQC) Project II, managed by FDA and was leader of the bioinformatics effort for the prostate cancer research group at Weill Cornell Medical College. In 2011 she joined the Centre for Integrative Biology at the University of Trento, Italy, where she is group leader (Computational Oncology Laboratory) and maintains Adjunct position at the Institute for Computational Biomedicine at Weill Cornell Medical College.

Genetic diversity and somatic mutations provide cancer a selective advantage to develop and progress. 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 and that structural variants such as inversions and Copy Number Variants (CNVs) add to the diversity encoded in single DNA base-pair difference, referred to as Single Nucleotide Polymorphism (SNPs). Emerging data from a number of groups supports the view that inherited variants are associated with increased risk of developing specific diseases including cancer. We also observe how common solid tumors, like prostate cancer, in fact hinder dramatic genomic complexity and seem to be a compendium of distinct homogenous tumor subclasses rather than one tumor type. The research focus of our laboratory is to untangle the effects of diversity on genomic complexity focusing on prostate cancer as the disease model.

In a highly interdisciplinary and systems biology framework, our group contributes to the understanding of the genomic complexity, which defines human tumors and of the involvement of inherited genetic make-up through the development and application of computational tools for genome-wide array based and next generation sequencing data. Our group is currently working on Whole Genome and Whole Exome Sequencing 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 quantification. We are also designing, implementing and analyzing validation studies using human samples collected from the Harvard/Michigan/Cornell Early Detection Research Network clinical trial (U.S.A.) and the Tyrol Prostate Specific Antigen Screening Trial (Austria).
Specific projects include:

Towards Understanding the Genetic Predisposition for Signaling Pathway Activation in Aggressive Prostate Cancer (funded by The Department of Defense, USA)
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)
Identification and functional characterization of inherited CNVs at a single locus and at biological pathway level.
Population based prostate cancer susceptibility study on the Tyrol Early Prostate Cancer Detection Program.
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)

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.

Setlur SR, Chen CX, Hossain RR, Ha JS, Van Doren VE, Stenzel B, Steiner E, Oldridge D, Katabayashi N, Banerjee S, Chen JY, Schäfer G, Horninger W, Lee C, Rubin MA, Klocker H, and Demichelis F. Genetic Variation of Genes involved in Dihydrotestosterone Metabolism and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev. 2010 Jan;19(1):229-39.

Oldridge DA, Banerjee S, Setlur SR, Sboner A, Demichelis F. Optimizing Copy Number Variation Analysis using Genome-Wide Short Sequence Oligonucleotide Arrays. Nucleic Acids Res 2010 Jun;38(10):3275-86.

David S. Rickman, Ying-bei Chen, Samprit Banerjee, Yihang Pan, Jindan Yu, Sven Perner, Christopher Lafargue, Kirsten D. Mertz, Sunita R. Setlur, Kanishka Sircar, Arul M. Chinnaiyan, Tarek A. Bismar, Mark A. Rubin and F. Demichelis. ERG Cooperates with Androgen Receptor in Regulating Trefoil Factor 3 in Prostate Cancer Disease Progression. Neoplasia 2010 Dec:12(12).

No projects are available to students for the current accademic year.