Photo of Roberto Chiarle,  MD

Roberto Chiarle, MD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2662
Fax: (617) 730-0148

Roberto Chiarle, MD

Boston Children's Hospital


  • Associate Professor, Pathology, Harvard Medical School
  • Research PI, Pathology, Boston Children's Hospital


Research Abstract

My laboratory is interested in mechanisms and therapy of cancers. In the past years, I have been working on different types of hematologic and solid cancers. Most lymphomas, but also an increasing number of solid tumors, are characterized by defined chromosomal translocations. The products of such translocations control tumor growth, confer precise biological characteristics to the tumors and can be targeted by specific therapies. In lymphoma, the translocations involving the Anaplastic Lymphoma Kinase (ALK) gene are characteristic of Anaplastic Large Cell Lymphoma (ALCL), but were recently found also in Non-Small Cell Lung Cancers (NSCLC) and other type of solid tumors. We have extensively studied the role of ALK in lymphoma and discovered multiple pathways essential to induce cellular transformation. By exploiting xenografts and mouse models for ALCL and NSCLC, and also neuroblastoma, we want to define relevant mechanisms of ALK-mediated transformation in vivo but also to validate therapeutic approaches to target ALK in such cancers. We are currently implementing innovative therapies such as ALK inhibitors, ALK-targeted siRNA and ALK-directed cancer immunotherapy. In this context, we developed a vaccination protocol that generates a strong ALK-specific immunization and seek to explore its potential use in clinical protocols.

Another main focus of the lab is to elucidate the mechanisms that govern the formation of chromosomal translocations in normal and neoplastic cells. In collaboration with other researches, we developed a method to map translocations at a genome-wide level, thus initiating a series of studies aimed at defining general rules for translocation formation, focusing on how transcription, DNA Double Strand Breaks (DBSs) availability and position, tissue specificity and other nuclear or DNA repair factors can influence the type and the frequency of translocations found in human cancers.

One more line of research in the lab is devoted to the discovery of novel genetic lesions in lymphoma and solid tumors, by modern techniques of next-generation sequencing. In particular, we recently co-discovered mutations in FBXO11, a gene involved in the degradation of BCL6 in human lymphomas. We aim at expanding these findings to other lymphomas or solid tumors, and at generating mouse models to uncover the roles of these genes in normal B cell development and lymphoma formation.


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  • Karreth FA, Reschke M, Ruocco A, Ng C, Chapuy B, Léopold V, Sjoberg M, Keane TM, Verma A, Ala U, Tay Y, Wu D, Seitzer N, Velasco-Herrera MD, Bothmer A, Fung J, Langellotto F, Rodig SJ, Elemento O, Shipp MA, Adams DJ, Chiarle R, Pandolfi PP. The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo. Cell 2015. PubMed
  • Alberti D, Protti N, Toppino A, Deagostino A, Lanzardo S, Bortolussi S, Altieri S, Voena C, Chiarle R, Geninatti Crich S, Aime S. A theranostic approach based on the use of a dual boron/Gd agent to improve the efficacy of Boron Neutron Capture Therapy in the lung cancer treatment. 2015; 11:741-50. PubMed
  • Voena C, Peola S, Chiarle R. The anaplastic lymphoma kinase as an oncogene in solid tumors. Front Biosci (Schol Ed) 2015; 7:269-82. PubMed
  • Blasco RB, Karaca E, Ambrogio C, Cheong TC, Karayol E, Minero VG, Voena C, Chiarle R. Simple and rapid in vivo generation of chromosomal rearrangements using CRISPR/Cas9 technology. Cell Rep 2014; 9:1219-27. PubMed
  • Ambrogio C, Carmona FJ, Vidal A, Falcone M, Nieto P, Romero OA, Puertas S, Vizoso M, Nadal E, Poggio T, Sánchez-Céspedes M, Esteller M, Mulero F, Voena C, Chiarle R, Barbacid M, Santamaría D, Villanueva A. Modeling Lung Cancer Evolution and Preclinical Response by Orthotopic Mouse Allografts. Cancer Res 2014. PubMed
  • Martinengo C, Poggio T, Menotti M, Scalzo MS, Mastini C, Ambrogio C, Pellegrino E, Riera L, Piva R, Ribatti D, Pastorino F, Perri P, Ponzoni M, Wang Q, Voena C, Chiarle R. ALK-Dependent Control of Hypoxia-Inducible Factors Mediates Tumor Growth and Metastasis. Cancer Res 2014. PubMed
  • Lattanzio R, La Sorda R, Facciolo F, Sioletic S, Lauriola L, Martucci R, Gallo E, Palmieri G, Evoli A, Alessandrini G, Ruco L, Rendina EA, Truini M, Chiarle R, Barreca A, Pich A, Ascani S, Remotti D, Tunesi G, Granone P, Ratto GB, Puma F, Pescarmona E, Piantelli M, Marino M, , Carlini S, Cerasoli V, Corzani F, Melis E, Filippetti M, Canalini P, Palestro G, Lalle M, Ruffini E, Ceribelli A, Rinaldi M. Thymic epithelial tumors express vascular endothelial growth factors and their receptors as potential targets of antiangiogenic therapy: a tissue micro array-based multicenter study. Lung Cancer 2014; 85:191-6. PubMed
  • Gostissa M, Schwer B, Chang A, Dong J, Meyers RM, Marecki GT, Choi VW, Chiarle R, Zarrin AA, Alt FW. IgH class switching exploits a general property of two DNA breaks to be joined in cis over long chromosomal distances. Proc Natl Acad Sci U S A 2014; 111:2644-9. PubMed
  • Semrau S, Crosetto N, Bienko M, Boni M, Bernasconi P, Chiarle R, van Oudenaarden A. FuseFISH: robust detection of transcribed gene fusions in single cells. Cell Rep 2014; 6:18-23. PubMed
  • Marino F, Orecchia V, Regis G, Musteanu M, Tassone B, Jon C, Forni M, Calautti E, Chiarle R, Eferl R, Poli V. STAT3硫 controls inflammatory responses and early tumor onset in skin and colon experimental cancer models. Am J Cancer Res 2014; 4:484-94. PubMed
  • Crosetto N, Mitra A, Silva MJ, Bienko M, Dojer N, Wang Q, Karaca E, Chiarle R, Skrzypczak M, Ginalski K, Pasero P, Rowicka M, Dikic I. Nucleotide-resolution DNA double-strand break mapping by next-generation sequencing. Nat Methods 2013; 10:361-5. PubMed
  • Chiarle R. Translocations in normal B cells and cancers: insights from new technical approaches. Adv Immunol 2013; 117:39-71. PubMed
  • Duan S, Cermak L, Pagan JK, Rossi M, Martinengo C, di Celle PF, Chapuy B, Shipp M, Chiarle R, Pagano M. FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature 2012; 481:90-3. PubMed
  • Chiarle R, Zhang Y, Frock RL, Lewis SM, Molinie B, Ho YJ, Myers DR, Choi VW, Compagno M, Malkin DJ, Neuberg D, Monti S, Giallourakis CC, Gostissa M, Alt FW. Genome-wide Translocation Sequencing Reveals Mechanisms of Chromosome Breaks and Rearrangements in B Cells. Cell 2011; 147:107-19. PubMed
  • Gostissa M, Alt FW, Chiarle R. Mechanisms that Promote and Suppress Chromosomal Translocations in Lymphocytes. Annu Rev Immunol 2011; 29:319-50. PubMed
  • Chiarle R, Martinengo C, Mastini C, Ambrogio C, D'Escamard V, Forni G, Inghirami G. The anaplastic lymphoma kinase is an effective oncoantigen for lymphoma vaccination. Nat Med 2008; 14:676-80. PubMed
  • Chiarle R, Voena C, Ambrogio C, Piva R, Inghirami G. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat Rev Cancer 2007; 8:11-23. PubMed
  • Chiarle R, Simmons WJ, Cai H, Dhall G, Zamo A, Raz R, Karras JG, Levy DE, Inghirami G. Stat3 is required for ALK-mediated lymphomagenesis and provides a possible therapeutic target. Nat Med 2005; 11:623-9. PubMed