EDUCATION:

1982-1987 Classic Lyceum

1987-1993 University of Torino Medical School, Italy: M.D. (summa cum laude)

1993-1997 University of Torino Medical School, Italy: Residency in Anatomic Pathology (summa cum laude)

ACADEMIC TRAINING:

1990-1991 Internship, Department of Radiology, University of Torino Medical School

1991-1992 Internship, Department of Medicine, University of Torino Medical School

1992-1993 Internship, Department of Pathology, University of Torino Medical School

POSTDOCTORAL TRAINING:

1996 -2001 Research Fellow, Department of Pathology, New York University Medical Center

2001-2006 Researcher, Department of Pathology, University of Torino Medical School

BOARD CERTIFICATION:
1997 Surgical Pathology, University of Torino Medical School

POSITION AND APPOINTMENTS:

RESEARCH

1996-2001: Research Fellow, Pathology, New York University (supervisors: Prof. G. Inghirami, New York University and Prof. M. Pagano, New York University and Howard Hughes Medical Institute)

2001-2006: Assistant Professor, Pathology, University of Torino, Italy

2006-present: Associate Professor with tenure, Pathology, University of Torino, Italy

2008-present: Visiting Associate Professor, Dept. of Pathology and Genetics, Children"s Hospital and Harvard Medical School, Boston (Prof. Fred W. Alt Laboratory)

CLINICAL ACTIVITY

2001-present: Attending Physician, General Clinical Pathology Physician, University of Torino Medical School and "San Giovanni Battista Hospital", Torino, Italy

2001-present: Attending Physician, Hematopathology and Diagnostic Molecular Pathology, University of Torino Medical School and "San Giovanni Battista Hospital", Torino, Italy


HONORS and AWARDS:

2001: Young investigator award, the University of Torino, Italy

2006: Italian National Prize "Premio Sapio" for Research - Junior Investigator Award

2007: "Premio G. Costa" for Basic Research

2009: European Research Council Starting Grant (ERC-StG) Investigator Award

2010: Italian National prize for Research in Oncology "Carlo Chianello" Foundation

SCIENTIFIC SOCIETIES:

European Association for Hematopathology (EAHP)

Italian Society of Anatomic Pathology (SIAPEC)




FORMAL TEACHING:

Courses in the MD program, University of Torino, Italy

2002-present: Haematopathology and immune diseases

2002-present: Pathology of the gastrointestinal tract and infectious diseases

2002-present: Surgical Pathology

2002-present: Diagnostic Molecular Pathology

Courses in Residency programs, University of Torino, Italy

2002-present: Diagnostic in Immunohistochemistry " Residency in Surgical Pathology

2002-present: Diagnostic in Flow Cytometry " Residency in Clinical Biochemistry

2002-present: Diagnostic in Histology " Residency in Oral and Maxillofacial Surgery


SUPERVISORY TEACHING and MENTORING:

Advisory committees:
2002 " present: Member, Thesis committee, University of Torino Medical School
2004 " present: Board Member, PhD programme in Human Oncology, University of Torino Medical School

Students directly supervised:
2003 " 2009 Chiara Ambrogio, Ph.D student, University of Torino
2003 " 2009 Francesco Boccalatte, Ph.D student, University of Torino
2005 " present Cinzia Martinengo, Ph.D student, University of Torino
2007 " present Cristina Mastini, Post Doc, University of Torino
2007 " present Matteo Menotti, BS graduate student, University of Torino
2009 " present Roberta Pulito, Ph.D student, University of Torino
2010 " present Ramesh Choudhari, Ph.D student, University of Torino

Ongoing projects in my laboratory in Torino, Italy
In this lab, I currently pursuing projects financed by the Italian government or by Italian foundations as well as by the European Community (ERC starting grant). These projects focus on the role of ALK as an oncogene in paediatric tumors such as lymphoma and neuroblastoma, and in adult cancer such as lung carcinoma. I selected a wide approach based both on the study of clinical samples from human patients, as well as on mouse models of these diseases. The approach is basic-translational, with the end goal of developing innovative therapeutic strategies to be used in this subset of diseases.
The outlines of this area of research are:
- Development of specific ALK tyrosine kinase inhibitors to inhibit the growth and survival of ALK lymphomas in vitro and in vivo (Project in collaboration with the company Cephalon, Inc. PA USA) in lymphomas, lung carcinoma and neuroblastoma
- Antitumor vaccination against ALK in lymphomas, in lung cancer and neuroblastoma
- In vitro and in vivo delivery of siRNA and ASO to target ALK and downstream effectors in ALCL and neuroblastoma
- Role of ALK tyrosine kinase in lymphoma cell growth, senescence and cooperation with antigenic stimulation to induce transformation of T cells
- Gene expression profiling, phosphoproteomic analysis on clinical samples of paediatric and adult ALCL
- Role of ALK in the pathogenesis of lung carcinoma through the analysis of clinical samples and the generation of mice expressing EML4-ALK in the lung for the generation of therapeutic strategies based on ALK tyrosine kinase inhibitors, ALK vaccination and ALK targeting by siRNA
- Role of ALK in the pathogenesis of neuroblastoma addressed by the generation of conditional knock-in mice carrying activating mutations of ALK.
- Molecular characterizations of other types of lymphomas (follicular lymphoma, T-cell lymphomas and Hodgkin Lymphomas, projects inside European networks)

Ongoing projects as Visiting Professor in Fred W. Alt lab, Harvard University
To expand my interest to broader questions such as the mechanistic events underlying chromosomal translocations that are frequent in pediatric cancers such as leukemia, lymphoma or soft tissue tumors, in November 2008 I joined Fred W. Alt lab at the Immune Disease Institute, Children’s Hospital and Harvard Medical School, Boston, as a Visiting Associate Professor. Recurrent translocations in tumors are often considered to represent very low frequency events that are strongly selected at the cellular level. However, mechanistic factors that have the ability to substantially influence the frequency of translocations need still to be fully elucidated. Such mechanistic factors include the frequency of DNA Double Strand Breaks (DSB) at two loci, the spatial proximity of the two loci, and the repair pathways functionally available to carry out the actual joining of DSBs. To gain further insights into mechanisms that promote translocations, I have developed a high-throughput next generation sequencing system to clone translocations from a fixed DSB in cycling primary B cells. In this system, I-SceI-mediated DSBs are generated either at the site of the IgG1 switch region within the IgH locus or within the c-myc proto-oncogene locus. The system worked very efficiently and our preliminary data show that translocations from defined DSBs are mostly AID dependent and, more frequently, are generated within loci in the same chromosome rather than different chromosomes. Thus, unbiased genome-wide analysis of translocation formation reveals non-random translocation patterns that highlight the importance of mechanistic factors, such as DSB frequency and location, and the organization of chromosomes within the nucleus. These results have great implications on the interpretation of data obtained from cancer genome sequencing projects.
The outlines of this area of research are:
- Elucidation of the mechanisms of translocations through the generation of an unbiased large scale translocation library from fixed Double Strand Breaks (DSB) located in defined positions in the IgH or c-myc loci in the mouse genome by massive sequencing
- Generation of a mouse model to induce translocations in vivo and ex vivo by targeting an inducible form of the I-SceI enzyme to generate defined DSB in the genome
- Generation of translocation libraries from human lymphoid B cells, and potentially other cell types, obtained from normal subjects or patients carrying functional deficiencies of molecules involved in the DNA repair pathways as found in different human diseases.

Piva R*, Chiarle R*§, Manazza AD*, Taulli R, Simmons W, Ambrogio C, D'Escamard V, Pellegrino E, Ponzetto C, Palestro G, Inghirami G. Ablation of oncogenic ALK is a viable therapeutic approach for anaplastic large-cell lymphomas. Blood. 2006 Jan 15;107(2):689-97.
* These authors equally contributed to the work, § Corresponding Author

Ambrogio C, Voena C, Manazza AD, Piva R, Riera L, Barberis L, Costa C, Tarone G, Defilippi P, Hirsch E, Erba EB, Mohammed S, Jensen ON, Palestro G, Inghirami G, Chiarle R. p130Cas mediates the transforming properties of the anaplastic lymphoma kinase. Blood. 2005 Dec 1;106(12):3907-16

Inghirami G, Chiarle R, Simmons WJ, Piva R, Schlessinger K, Levy DE. New and old functions of STAT3: a pivotal target for individualized treatment of cancer. Cell Cycle. 2005 Sep;4(9):1131-3.

Piva R, Pellegrino E, Mattioli M, Agnelli L, Lombardi L, Boccalatte F, Costa G, Ruggeri BA, Cheng M, Chiarle R, Palestro G, Neri A, Inghirami G. Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and BCL2A1 as critical target genes. J Clin Invest. 2006 Dec;116(12):3171-82.

Conti L, Regis G, Longo A, Bernabei P, Chiarle R, Giovarelli M, Novelli F. In the absence of IGF-1 signaling, IFN-gamma suppresses human malignant T-cell growth. Blood. 2007 Mar 15;109(6):2496-

Voena C, Conte C, Ambrogio C, Boeri Erba E, Boccalatte F, Mohammed S, Jensen ON, Palestro G, Inghirami G, Chiarle R. The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration. Cancer Res. 2007 May 1;67(9):4278-86.

Costa C, Barberis L, Ambrogio C, Manazza AD, Patrucco E, Azzolino O, Neilsen PO, Ciraolo E, Altruda F, Prestwich GD, Chiarle R, Wymann M, Ridley A, Hirsch E. Negative feedback regulation of Rac in leukocytes from mice expressing a constitutively active phosphatidylinositol 3-kinase {gamma}. Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14354-9.

Chiarle R, Voena C, Ambrogio C, Piva R, Inghirami G. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat Rev Cancer. 2008 Jan;8(1):11-23.

Chiarle R, Martinengo C, Mastini C, Ambrogio C, D’Escamard V, Forni G, Inghirami G. Anaplastic Lymphoma Kinase is an effective oncoantigen for lymphoma vaccination. Nat Medicine. 2008 Jun;14(6):676-80

Ambrogio C, Voena C, Manazza AD, Martinengo C, Costa C, Kirchhausen T, Hirsch E, Inghirami G, Chiarle R. The anaplastic lymphoma kinase controls cell shape and growth of anaplastic large cell lymphoma through Cdc42 activation. Cancer Res. 2008 Nov 1;68(21):8899-907.

Boccalatte FE, Voena C, Riganti C, Bosia A, D'Amico L, Riera L, Cheng M, Ruggeri B, Jensen ON, Goss VL, Lee K, Nardone J, Rush J, Polakiewicz RD, Comb MJ, Chiarle R, Inghirami G. The enzymatic activity of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) is enhanced by NPM-ALK: new insights in ALK-mediated pathogenesis and the treatment of ALCL. Blood. 2009 Mar 19;113(12):2776-90.

Mastini C, Martinengo C, Inghirami G, Chiarle R. Anaplastic lymphoma kinase: an oncogene for tumor vaccination. J Mol Med. 2009 Jul;87(7):669-77.

Regis G, Icardi L, Conti L, Chiarle R, Piva R, Giovarelli M, Poli V, Novelli F. IL-6, but not IFN-gamma, triggers apoptosis and inhibits in vivo growth of human malignant T cells on STAT3 silencing. Leukemia. 2009 Nov;23(11):2102-8.

Ambrogio C, Martinengo C, Voena C, Tondat F, Riera L, di Celle PF, Inghirami G, Chiarle R. NPM-ALK oncogenic tyrosine kinase controls T-cell identity by transcriptional regulation and epigenetic silencing in lymphoma cells. Cancer Res. 2009 Nov 15;69(22):8611-9.

Gonzalo P, Guadamillas MC, Hernández-Riquer MV, Pollán A, Grande-García A, Bartolomé RA, Vasanji A, Ambrogio C, Chiarle R, Teixidó J, Risteli J, Apte SS, del Pozo MA, Arroyo AG. MT1-MMP is required for myeloid cell fusion via regulation of Rac1 signaling. Dev Cell. 2010 Jan 19;18(1):77-89

Riera L, Lasorsa E, Ambrogio C, Surrenti N, Voena C, Chiarle R. Involvement of Grb2 adaptor protein in nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-mediated signaling and anaplastic large cell lymphoma growth. J Biol Chem. 2010 Aug 20;285(34):26441-50.

Zhang Y, Gostissa M, Hildebrand DG, Becker MS, Boboila C, Chiarle R, Lewis S, Alt FW. The Role of Mechanistic Factors in Promoting Chromosomal Translocations Found in Lymphoid and Other Cancers. Adv Immunol. 2010;106C:93-133.

Bachetti T, Di Paolo D, Di Lascio S, Mirisola V, Brignole C, Bellotti M, Caffa I, Ferraris C, Fiore M, Fornasari D, Chiarle R, Borghini S, Pfeffer U, Ponzoni M, Ceccherini I, Perri P. POX2B-mediated regulation of ALK expression: in vitro identification of a functional relationship between two genes involved in neuroblastoma. PLoS One. 2010 Oct 1;5(10). pii: e13108.

Gostissa M, Alt FW, Chiarle R. Mechanisms that promote and suppress chromosomal translocations in lymphocytes. Annu. Rev. Immunol. 2011 Apr 23;29:319-50.

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