Universita’ Degli Studi Di Milano- Bicocca

Short Name: UNIMIB

Country: IT

Website: www.UNIMIB.it

Organization description:

The University of Milano-Bicocca is a public, state-funded, multidisciplinary academic institution. Research Centres cooperate with public and private third parties, and are managed according to guidelines that guarantee high scientific standards. UNIMIB has a Medical School that offer training in medicine, surgery, public health, and operate in collaboration with the University hospital San Gerardo, both located in Monza. With 900 beds, 20 operating theatres, intensive care units, 50 departments and specialized units, a complete range of diagnostic services and more than 3,000 health care professionals, the hospital is the fourth largest in Lombardy Region. It will cooperate with the high level institutions involved in the project to diffuse technology and experience also among the other health institutions of the area.

UNIMIB intensely promote the translation of research results supporting the technology transfer. The operating structure involved in this project is Department of Medicine and Surgery that will provide the resources and expertise to carry out the project activities. The department has developed extensive expertise in clinical and translational research, with the aim of supporting medical and biotechnological development and technology transfer. Main expertise include the study of different physio-pathological processes for the development of new diagnostic and therapeutic tools and accelerate the transfer from basic science to clinics in the fields of oncology, immunology, transplantation, rare diseases. Diagnostic and therapeutic projects benefit from interdisciplinary collaborations.

 

Expertise:

Research, education and training, clinical care, biobanking, biomarker development, bioinformatics, management, Ethical-Legal-Societal-Issues.

Facilities: The department operates fully equipped laboratories for molecular and cellular analyses as well as for histological and immunohistochemistry analyses (Laser capture microdissection, Tissue Micro Array, Microspy, real-time PCR, DNA microarrays, NGS-sequencing) supported by technological platforms for the -omics analysis of tissue samples from patients.

Equipment includes robotic automation, ultracentrifuges, laminar flow hoods, CO2 incubators, refrigerated centrifuges, direct and inverted microscopes, Fluorescence Activated Cell Sorters, sonicators, electron microscopes, liquid nitrogen storage facility, cellular irradiator, controlled rate cell freezer, electrophoresis tools, PCR and Q-PCR instruments, dark room, sequencing instruments.

Other European projects:

 

 

Other relevant projects:

  • International study focused on the dissection of the driver events responsible for the onset and clonal evolution of atypical chronic myeloid leukemia
  • Italian Association for Cancer Research – Investigator Grant 2018 Characterization of the somatic and germline mutation landscape of Triple Negative Myeloproliferative Neoplasms

Role in the project:

UNIMIB is responsible to lead work package 6 which is dedicated to 6 Ethics, data privacy and security. UNIMIB will be responsible to lead the tasks related to the identification of ethics, legal (incl. data privacy) and social issues (ELSI) key to the development and exploitation of improved NGS technique as well as the engagement with patients, patients’ organizations, public and stakeholders in the field. UNIMIB will also address appropriately specific ELSI issues: e.g. informed consent, information and assent for minors, guidelines for the management of incidental findings, compliance with GDPR and data protection and privacy, access based on FAIR principles, as well as the questions related to intellectual property rights, the need for pan-European trainings. UNIMIB will be actively involved in WP1 management; in WP2 contributing to define specification of medical, technical, regulatory and health economic requirements for NGS for routine diagnostics in Paediatric & Adult Oncology; in the downstream WP3 (Creation of specific calls for tenders) and WP4 (Implementation of contracts), including the process to select suppliers and in the evaluation of their performance; in WP5 (Stakeholders’ engagement, Communication, dissemination and Exploitation of project results) co-leading the task on education and training; WP7 (Development of the specific NGS requirements in the standardisation activities for routine diagnostics with specific EQA developed).

 

Key personnel:

Prof. Dr. Marialuisa Lavitrano

Prof. Dr. Marialuisa Lavitrano (female), Full Professor of Pathology, Director of the School of Medical Oncology, Director of Molecular Medicine Unit Department of Medicine and Surgery University of Milano-Bicocca where she was pro-rector for International Affairs for 8 years (2006–2013). Prof. Lavitrano is member of Research and Health Ministries joint Commission for strategic planning. For four years, she developed the international strategies for the Ministry of Health, participated to the Inter-ministerial Commission for International Research – JPI, Road map ESFRI, EraNet, IMI – for strategic planning and evaluation of grant proposal, BioMedical Science sector, and coordinated the Italian participation in the BioMedical Sciences ESFRI roadmap.

Prof. Lavitrano participated in the preparatory phase of BBMRI as the Italian member state representative and in 2013 has been appointed as BBMRI Italy Node Director, the national node of the pan-European Biobanking and Biomolecular Resources Research Infrastructure (BBMRI- ERIC); co-director ELSI common service BBMRI-ERIC (2014-2018).

Prof. Lavitrano has a long-term experience in managing R&D projects and carried out cutting edge research projects through a translational approach for transferring research results. She also founded a university spin-off for the development of tumor bio-markers and of modulator compounds of drug resistance in epithelial tumors. Moreover, she is interested in the bioethical aspects of science and research and participated at Bioethic Commissions of the Council of Europe and of the Vatican (1999-2004), and of the Italian government (2005-present), moreover Prof. Lavitrano is co-director of BBMRI-ERIC Common Service on Ethical, Legal and Society Issues (2014-present). Prof. Lavitrano in the last 10 years published 58 articles (source ISI WOS) in international peer review journals

Expertise: Molecular and Translational Medicine, discovering of new biomarkers, biobanking, Ethics.

Capacity and resources: Command of all procedures of gene expression, manipulation and transfer and cell biology and –omics techniques. Access to facilities for molecular cell and tissues analyses and to NGS platform.

 

Prof Dr. Rocco Giovanni Piazza

Prof Dr. Rocco Giovanni Piazza (male), associate professor in hematology. Prof. Piazza holds a dual appointment as an assistant professor and PI at the University of Milano-Bicocca in Monza and as a clinical hematologist at the San Gerardo Hospital in Monza. He and his team have made major contributions in the field of myelodysplastic/myeloproliferative disorders, including the identification and characterization of new driver oncogenes such as SETBP1 and ETNK1 that are now part of the recent WHO classification of hematological malignancies and seminal studies on the use of Crizotinib in advanced, chemo-resistant anaplastic lymphoma kinase-positive lymphoma patients.

Prof. Piazza started working in the field of NGS for the detection of somatic variants back in 2009 with one of the first human-scale NGS instruments, the Illumina Genome Analyzer IIx. Since then he and his team focused on the development of a comprehensive approach dedicated to the identification and functional characterization of driver somatic mutations occurring in hematological cancers. We initially identify key driver events in target cancers and then translate them into cellular and molecular models, using CRISPR/Cas9 tools as well as classical transfection and viral infection techniques with the final goal of dissecting the molecular function(s) of the target variants. Prof. Piazza coordinates an international study devoted to the dissection of the driver events responsible for the onset and clonal evolution of atypical chronic myeloid leukemia.

Expertise: NGS, both wet-lab and bioinformatics, comprising exome sequencing, whole- transcriptome assays (RNA-Seq), differential gene expression analysis as well as for gene fusion detection, targeted capture- and amplicon-based panels, ChIP-Seq, ATAC-Seq, Reduced representation bisulfite sequencing (RRBS), 16S microbiome and metagenome analyses.

As a NGS expert in the last year Prof. Piazza analysed more than 2000 cancer samples, comprising capture and amplicon-based panels, whole-exomes, whole-transcriptome, targeted RNA-Seq, RRBS and ultradeep-seq.

 

Prof Dr. Marco Antoniotti

 

Prof Dr. Marco Antoniotti (Male) associate professor Bioinformatics.

Prof Marco Antoniotti obtained his Ph.D. and M.S. in Computer Science form the Courant Institute of Mathematical Sciences of New York University in 1995 and 1992. His current research interests are in Bioinformatics and Computational Biology; Simulation, Verification and Language Design Issues in Embedded and Hybrid Systems. Prof. Antoniotti is the author of several journal and conference papers and the author or director of several software projects. Prof. Antoniotti was a recipient of a Marie Curie IRG grant for the BRONTE project and was a co-P.I. in a project funded under the U.S. N.S.F. Emerging Models and Technologies for Computation. In 2010-2012 he was the recipient of the Lombardy Region ASTIL grant for the RetroNet Project, which led to research in the field of “Cancer Progression Models”. In 2016 he has been named to the MC of COST Action CA15110 CHARME and has received the ELIXIR-ITA grant to support National Bioinformatics Infrastructures. Prof. Antoniotti has been the director of the yearly Lake Como Workshop and School on Cancer, Development and Complexity since 2014. He is one of the P.I. of the BIMIB group in the Dipartimento di Informatica, Sistemistica e Comunicazione dell’Università degli Studi di Milano Bicocca. He is a member of IEEE and ISCB.

Expertise: Bioinformatics and Computational Biology; Simulation, Verification and Language Design Issues in Embedded and Hybrid Systems

 

Dr. Sara Casati

Dr. Sara Casati, PhD (Female) Research Fellow

Clinical bioethicist by training but a practical philosopher by imprinting, she studied in Milan, Paris, Siena, London and Madrid developing together with patients, professionals, institutions, inclusive models for a participatory medicine and a collaborative biomedical research. After her “Magister in Bioética Clinica” and her first PhD on “Ethical deliberation and good clinical practice” earned from both the Universidad Complutense –  Madrid and the Università degli studi di Siena,

she was twice nationally awarded for her research in action, carried to check an innovative governance of informed consent and to model empowerment settings with a focus on vulnerability scenarios. At the forefront with Eurordis, UNIAMO F.I.M.R. onlus and many  patient Organizations, she directs national projects dealing with ELSI issues of advanced research.

Dr. Casati is member of the ELSI common service of BBMRI-ERIC and of BBMRI.it (2014 to present)

Expertise: Ethical deliberation and good clinical practice, patients involvement and empowerment, biobanking

 

Main publications and awards:

Publications:

Sala, L., Cirillo, G., Riva, G., Romano, G., Giussani, C., Cialdella, A., et al. (2019). Specific Expression of a New Bruton Tyrosine Kinase Isoform (p65BTK) in the Glioblastoma Gemistocytic Histotype. FRONTIERS IN MOLECULAR NEUROSCIENCE, 12.

Daniele Ramazzotti, Alex Graudenzi, Luca De Sano, Marco Antoniotti, Giulio Caravagna, Learning Mutational Graphs of Individual Tumor Evolution from Single-cell and Multi-region Sequencing Data, BMC Bioinformatics, to appear, 2019.

Holub, P., Kohlmayer, F., Prasser, F., Mayrhofer, M., Schlünder, I., Martin, G., et al. (2018). Enhancing Reuse of Data and Biological Material in Medical Research: From FAIR to FAIR- Health. BIOPRESERVATION AND BIOBANKING, 16(2), 97-105.

Alex Graudenzi, Davide Maspero, Marzia Di Filippo, Marco Grugnoli, Claudio Isella, Giancarlo Mauri, Enzo Medico, Marco Antoniotti, Chiara Damiani, Integration of transcriptomic data and metabolic networks in cancer samples reveals highly significant prognostic power, Journal of Biomedical Informatics, 2018, doi:10.1016/j.jbi.2018.09.010

Conconi, D., Villa, N., Redaelli, S., Sala, E., Crosti, F., Maitz, S., et al. (2018). Familiar unbalanced complex rearrangements involving 13 p-arm: Description of two cases. MOLECULAR CYTOGENETICS, 11(1):52. doi: 10.1186/s13039-018-0400-6..

Cerrito MG, De Giorgi M, Pelizzoni D, Bonomo SM, Digiacomo N, Scagliotti A, Bugarin C, Gaipa G, Grassilli E, Lavitrano M, Giovannoni R, Bidoli P, Cazzaniga ME. Metronomic combination of Vinorelbine and 5Fluorouracil is able to inhibit triple-negative breast cancer cells. Results from the proof-of-concept VICTOR-0 study. ONCOTARGET. 2018 Jun 8;9(44):27448-27459.

Piazza R, Magistroni V, Redaelli S, Mauri M, Massimino L, Sessa A, Peronaci M, Lalowski M, Soliymani R, Mezzatesta C, Pirola A, Banfi F, Rubio A, Rea D, Stagno F, Usala E, Martino B, Campiotti L, Merli M, Passamonti F, Onida F, Morotti A, Pavesi F, Bregni M, Broccoli V, Baumann M, Gambacorti Passerini C, SETBP1 induces transcription of a network of development genes by acting as an epigenetic hub. Nat Commun. 2018 Jun 6;9(1):2192. doi: 10.1038/s41467- 018-04462-8

Romano, G., Reggi, S., Kutryb-Zajac, B., Facoetti, A., Chisci, E., Pettinato, M., et al. (2018). APOA-1Milano muteins, orally delivered via genetically modified rice, show anti-atherogenic and anti-inflammatory properties in vitro and in Apoe−/−atherosclerotic mice. INTERNATIONAL JOURNAL OF CARDIOLOGY.

Conconi D, Chiappa V, Perego P, Redaelli S, Bovo G, Lavitrano M, Milani R, Dalprà L, Lissoni AA. Potential role of BCL2 in the recurrence of uterine smooth muscle tumors of uncertain malignant potential.ONCOL REP. 2017 Jan;37(1):41-47. doi: 10.3892/or.2016.5274.

Silvestris, N., Ciliberto, G., De Paoli, P., Apolone, G., Lavitrano, M., Pierotti, M., et al. (2017). Liquid dynamic medicine and N-of-1 clinical trials: A change of perspective in oncology research. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 36(1).

  1. Caravagna, A. Graudenzi, D. Ramazzotti, R. Sanz-Pamplona, L. De Sano, G. Mauri, V. Moreno,
  2. Antoniotti, B. Mishra, Algorithmic Methods to Infer the Evolutionary Trajectories in Cancer Progression. Proceedings of the National Academy of Sciences (PNAS), June, 27, 2016, doi:10.1073/pnas.1520213113.

Kutryb-Zajac, B., Yuen, A., Khalpey, Z., Zukowska, P., Slominska, E., Taylor, P., et al. (2016). Nucleotide Catabolism on the Surface of Aortic Valve Xenografts; Effects of Different Decellularization Strategies. JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH, 9(2), 119-126.

Grassilli E, Pisano F, Cialdella A, Bonomo S, Missaglia C, Cerrito MG, Masiero L, Ianzano L, Giordano F, Cicirelli V, Narloch R, D’Amato F, Noli B, Ferri GL, Leone BE, Stanta G, Bonin S, Helin K, Giovannoni R, Lavitrano M. A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation. ONCOGENE. 2016 Aug 18;35(33):4368- 78.

  1. Ramazzotti, G. Caravagna, L. Olde Loohuis, A. Graudenzi, I. Korsunsky, G. Mauri, M. Antoniotti, B. Mishra, CAPRI: Efficient Inference of Cancer Progression Models from Cross- sectional Data, Bioinformatics, first published online: May 13, 2015, doi:10.1093/bioinformatics/btv296.

Mori S, Vagge E, le Coutre P, Abruzzese E, Martino B, Pungolino E, Elena C, Pierri I, Assouline S, D’Emilio A, Gozzini A, Giraldo P, Stagno F, Iurlo A, Luciani M, De Riso G, Redaelli S, Kim DW, Pirola A, Mezzatesta C, Petroccione A, Lodolo D’Oria A, Crivori P, Piazza R, Gambacorti-Passerini

  1. Age and dPCR can predict relapse in CML patients who discontinued imatinib: The ISAV study. Am J Hematol. 2015 Jul 15. doi: 10.1002/ajh.24120.

Di Savino A, Panuzzo C, Rocca S, Familiari U, Piazza R, Crivellaro S, Carrà G, Ferretti R, Fusella F, Giugliano E, Camporeale A, Franco I, Miniscalco B, Cutrin JC, Turco E, Silengo L, Hirsch E, Rege-Cambrin G, Gambacorti-Passerini C, Pandolfi PP, Papotti M, Saglio G, Tarone G, Morotti A, Brancaccio M. Morgana acts as an oncosuppressor in chronic myeloid leukemia. Blood. 2015 Apr 2;125(14):2245-53. doi: 10.1182/blood-2014-05-575001.

Gambacorti-Passerini C, Donadoni C, Parmiani A, Pirola A, Redaelli S, Signore G, Piazza V, Malcovati L, Fontana D, Spinelli R, Magistroni V, Gaipa G, Peronaci M, Morotti A, Panuzzo C, Saglio G, Usala E, Kim DW, Rea D, Zervakis K, Viniou N, Symeonidis A, Becker H, Boultwood J, Campiotti L, Carrabba M, Elli E, Bignell GR, Papaemmanuil E, Campbell PJ, Cazzola M, Piazza R. Recurrent ETNK1 mutations in atypical chronic myeloid leukemia. Blood. 2015 Jan 15;125(3):499- 503

Gambacorti Passerini C, Farina F, Stasia A, Redaelli S, Ceccon M, Mologni L, Messa C, Guerra L, Giudici G, Sala E, Mussolin L, Deeren D, King MH, Steurer M, Ordemann R, Cohen AM, Grube M, Bernard L, Chiriano G, Antolini L, Piazza R. Crizotinib in advanced, chemoresistant anaplastic

lymphoma  kinase-positive  lymphoma  patients.  J  Natl  Cancer  Inst.  J  Natl  Cancer  Inst.  2014 Feb;106(2):djt378. doi: 10.1093/jnci/djt378

Piazza R, Valletta S, Winkelmann N, Redaelli S, Spinelli R, Pirola A, Antolini L, Mologni L, Donadoni C, Papaemmanuil E, Schnittger S, Kim DW, Boultwood J, Rossi F, Gaipa G, De Martini GP, Francia di Celle P, Jang HG, Fantin V, Bignell GR, Magistroni V, Haferlach T, Pogliani EM, Campbell PJ, Chase AJ, Tapper WJ, Cross NCP, Gambacorti-Passerini C. Recurrent SETBP1 mutations in atypical chronic myeloid leukemia. Nat Genet. 2013 Jan;45(1):18-24

Grassilli E, Narloch R, Federzoni E, Ianzano L, Pisano F, Giovannoni R, Romano G, Masiero L, Leone BE, Bonin S, Donada M, Stanta G, Helin K, Lavitrano M. Inhibition of GSK3B bypass drug resistance of p53-null colon carcinomas by enabling necroptosis in response to chemotherapy. CLIN CANCER RES. 2013 Jul 15;19(14):3820-31

Bachmann PS*, Piazza RG*, Janes ME, Wong NC, Davies C, Mogavero A, Bhadri VA, Szymanska B, Geninson G, Magistroni V, Cazzaniga G, Biondi A, Miranda-Saavedra D, Göttgens B, Saffery R, Craig JM, Marshall GM, Gambacorti-Passerini C, Pimanda JE, Lock RB, (*Joint First Authors). Epigenetic silencing of BIM in glucocorticoid poor-responsive pediatric acute lymphoblastic leukemia, and its reversal by histone deacetylase inhibition. Blood. 2010 Oct 21;116(16):3013-22

Marega M*, Piazza RG*, Pirola A, Redaelli S, Mogavero A, Iacobucci I, Meneghetti I, Parma M, Pogliani EM, Gambacorti-Passerini C, (*Joint First Authors). BCR and BCR-ABL regulation during myeloid differentiation in healthy donors and in chronic phase/blast crisis CML patients. Leukemia. 2010 Aug;24(8):1445-9

Gambacorti-Passerini C, Gunby R, Piazza RG, Galietta A, Rostagno R, Scapozza L. Molecular mechanisms of resistance to imatinib in Philadelphia-chromosome-positive leukaemias. Lancet Oncology, 2003 Feb;4(2):75-85

Awards:

 

Prof. Lavitrano has been selected as a testimonial of European women scientists in the European project TWIST (Towards Women in Sciences and Technology, http://www.the-twist-project.eu).

Prof. Piazza is recipient of the ‘Bruno Farmaceutici’ Foundation Research Award (2014) for his seminal work in the field of Myelodysplastic/Myeloproliferative disorders.

Patents:

 

Prof. Lavitrano is co-inventor of 6 patents and 5 patent applications