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


  • 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.

Publications from Harvard Catalyst Profiles

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  • Tao J, Wang Q, Mendez-Dorantes C, Burns KH, Chiarle R. Frequency and mechanisms of LINE-1 retrotransposon insertions at CRISPR/Cas9 sites. Nat Commun 2022; 13:3685. PubMed
  • Ludwig LS, Lareau CA, Bao EL, Liu N, Utsugisawa T, Tseng AM, Myers SA, Verboon JM, Ulirsch JC, Luo W, Muus C, Fiorini C, Olive ME, Vockley CM, Munschauer M, Hunter A, Ogura H, Yamamoto T, Inada H, Nakagawa S, Ohzono S, Subramanian V, Chiarle R, Glader B, Carr SA, Aryee MJ, Kundaje A, Orkin SH, Regev A, McCavit TL, Kanno H, Sankaran VG. Congenital anemia reveals distinct targeting mechanisms for master transcription factor GATA1. Blood 2022; 139:2534-2546. PubMed
  • Aziz-Bose R, Wachter F, Chiarle R, Lindeman NI, Kim AS, Degar B, Davies K, Pikman Y. Rapid next generation sequencing aids in diagnosis of transient abnormal myelopoiesis in a phenotypically normal newborn. Blood Adv 2022. PubMed
  • Horiguchi H, Xu H, Duvert B, Ciuculescu F, Yao Q, Sinha A, McGuinness M, Harris C, Brendel C, Troeger A, Chiarle R, Williams DA. Deletion of murine leads to de-repression of via decreased KAISO levels and accelerates a malignancy phenotype in a murine model of lymphoma. 2022; 13:267-281. PubMed
  • Karaca Atabay E, Mecca C, Wang Q, Ambrogio C, Mota I, Prokoph N, Mura G, Martinengo C, Patrucco E, Leonardi G, Hossa J, Pich A, Mologni L, Gambacorti-Passerini CB, Brugieres L, Geoerger B, Turner SD, Voena C, Cheong TC, Chiarle R. Tyrosine phosphatases regulate resistance to ALK inhibitors in ALK+ anaplastic large cell lymphoma. Blood 2021. PubMed
  • Pighi C, Cheong TC, Compagno M, Patrucco E, Arigoni M, Olivero M, Wang Q, Lopez C, Bernhart SH, Grande BM, Poggio T, Langellotto F, Bonello L, Dall'Olio R, Martínez-Martín S, Molinaro L, Francia di Celle P, Whitfield JR, Soucek L, Voena C, Calogero RA, Morin RD, Staudt LM, Siebert R, Zamò A, Chiarle R. Frequent mutations of FBXO11 highlight BCL6 as a therapeutic target in Burkitt lymphoma. Blood Adv 2021. PubMed
  • Mucciolo G, Curcio C, Roux C, Li WY, Capello M, Curto R, Chiarle R, Giordano D, Satolli MA, Lawlor R, Scarpa A, Lukac P, Stakheev D, Provero P, Vannucci L, Mak TW, Novelli F, Cappello P. IL17A critically shapes the transcriptional program of fibroblasts in pancreatic cancer and switches on their protumorigenic functions. Proc Natl Acad Sci U S A 2021. PubMed
  • Rao S, Yao Y, Soares de Brito J, Yao Q, Shen AH, Watkinson RE, Kennedy AL, Coyne S, Ren C, Zeng J, Serbin AV, Studer S, Ballotti K, Harris CE, Luk K, Stevens CS, Armant M, Pinello L, Wolfe SA, Chiarle R, Shimamura A, Lee B, Newburger PE, Bauer DE. Dissecting ELANE neutropenia pathogenicity by human HSC gene editing. Cell Stem Cell 2021. PubMed
  • Sorrentino D, Frentzel J, Mitou G, Blasco RB, Torossian A, Hoareau-Aveilla C, Pighi C, Farcé M, Meggetto F, Manenti S, Espinos E, Chiarle R, Giuriato S. High Levels of miR-7-5p Potentiate Crizotinib-Induced Cytokilling and Autophagic Flux by Targeting RAF1 in NPM-ALK Positive Lymphoma Cells. Cancers (Basel) 2020. PubMed
  • Prokoph N, Probst NA, Lee LC, Monahan JM, Matthews JD, Liang HC, Bahnsen K, Montes-Mojarro IA, Karaca Atabay E, Sharma GG, Malik V, Larose H, Forde SD, Ducray SP, Lobello C, Wang Q, Luan SL, Pospisilova S, Gambacorti-Passerini CB, Burke A, Pervez S, Attarbaschi A, Janikova A, Pacquement H, Landman-Parker J, Lambilliotte A, Schleiermacher G, Klapper W, Jauch R, Woessmann W, Vassal G, Kenner L, Merkel O, Mologni L, Chiarle R, Brugieres L, Geoerger B, Barbieri I, Turner SD. IL10RA Modulates Crizotinib Sensitivity in NPM1-ALK-positive Anaplastic Large Cell Lymphoma. Blood 2020. PubMed
  • Baldacci S, Grégoire V, Patrucco E, Chiarle R, Jamme P, Wasielewski E, Descarpentries C, Copin MC, Awad MM, Cortot AB. Complete and prolonged response to anti-PD1 therapy in an ALK rearranged lung adenocarcinoma. Lung Cancer 2020. PubMed
  • Jiang C, Trudeau SJ, Cheong TC, Guo R, Teng M, Wang LW, Wang Z, Pighi C, Gautier-Courteille C, Ma Y, Jiang S, Wang C, Zhao B, Paillard L, Doench JG, Chiarle R, Gewurz BE. CRISPR/Cas9 Screens Reveal Multiple Layers of B cell CD40 Regulation. Cell Rep 2019; 28:1307-1322.e8. PubMed
  • Voena C, Chiarle R. RHO Family GTPases in the Biology of Lymphoma. Cells 2019. PubMed
  • Menotti M, Ambrogio C, Cheong TC, Pighi C, Mota I, Cassel SH, Compagno M, Wang Q, Dall'Olio R, Minero VG, Poggio T, Sharma GG, Patrucco E, Mastini C, Choudhari R, Pich A, Zamo A, Piva R, Giliani S, Mologni L, Collings CK, Kadoch C, Gambacorti-Passerini C, Notarangelo LD, Anton IM, Voena C, Chiarle R. Wiskott-Aldrich syndrome protein (WASP) is a tumor suppressor in T cell lymphoma. Nat Med 2018. PubMed
  • Sharma GG, Mota I, Mologni L, Patrucco E, Gambacorti-Passerini C, Chiarle R. Tumor Resistance against ALK Targeted Therapy-Where It Comes From and Where It Goes. Cancers (Basel) 2018. PubMed
  • Ambrogio C, Köhler J, Zhou ZW, Wang H, Paranal R, Li J, Capelletti M, Caffarra C, Li S, Lv Q, Gondi S, Hunter JC, Lu J, Chiarle R, Santamaría D, Westover KD, Jänne PA. KRAS Dimerization Impacts MEK Inhibitor Sensitivity and Oncogenic Activity of Mutant KRAS. Cell 2018; 172:857-868.e15. PubMed
  • Cheong TC, Blasco RB, Chiarle R. The CRISPR/Cas9 System as a Tool to Engineer Chromosomal Translocation In Vivo. Adv Exp Med Biol 2018; 1044:39-48. PubMed
  • Layer JV, Cleary JP, Brown AJ, Stevenson KE, Morrow SN, Van Scoyk A, Blasco RB, Karaca E, Meng FL, Frock RL, Tivey T, Kim S, Fuchs H, Chiarle R, Alt FW, Roberts SA, Weinstock DM, Day TA. Parp3 promotes long-range end joining in murine cells. Proc Natl Acad Sci U S A 2018; 115:10076-10081. PubMed
  • Awad MM, Mastini C, Blasco RB, Mologni L, Voena C, Mussolin L, Mach SL, Adeni AE, Lydon CA, Sholl LM, Jänne PA, Chiarle R. Epitope mapping of spontaneous autoantibodies to anaplastic lymphoma kinase (ALK) in non-small cell lung cancer. 2017; 8:92265-92274. PubMed
  • Gulluni F, Martini M, De Santis MC, Campa CC, Ghigo A, Margaria JP, Ciraolo E, Franco I, Ala U, Annaratone L, Disalvatore D, Bertalot G, Viale G, Noatynska A, Compagno M, Sigismund S, Montemurro F, Thelen M, Fan F, Meraldi P, Marchiò C, Pece S, Sapino A, Chiarle R, Di Fiore PP, Hirsch E. Mitotic Spindle Assembly and Genomic Stability in Breast Cancer Require PI3K-C2α Scaffolding Function. Cancer Cell 2017; 32:444-459.e7. PubMed
  • Platt CD, Fried AJ, Hoyos-Bachiloglu R, Usmani GN, Schmidt B, Whangbo J, Chiarle R, Chou J, Geha RS. Combined immunodeficiency with EBV positive B cell lymphoma and epidermodysplasia verruciformis due to a novel homozygous mutation in RASGRP1. Clin Immunol 2017; 183:142-144. PubMed
  • Nieto P, Ambrogio C, Esteban-Burgos L, Gómez-López G, Blasco MT, Yao Z, Marais R, Rosen N, Chiarle R, Pisano DG, Barbacid M, Santamaría D. A Braf kinase-inactive mutant induces lung adenocarcinoma. Nature 2017; 548:239-243. PubMed
  • Riccardo F, Réal A, Voena C, Chiarle R, Cavallo F, Barutello G. Maternal Immunization: New Perspectives on Its Application Against Non-Infectious Related Diseases in Newborns. Vaccines (Basel) 2017. PubMed
  • Song H, Todd P, Chiarle R, Billett AL, Gellis S. Primary Cutaneous B-Cell Lymphoblastic Lymphoma Arising from a Long-Standing Lesion in a Child and Review of the Literature. Pediatr Dermatol 2017; 34:e182-e186. PubMed
  • Fiorini C, Abdulhay NJ, McFarland SK, Munschauer M, Ulirsch JC, Chiarle R, Sankaran VG. Developmentally-Faithful and Effective Human Erythropoiesis in Immunodeficient and Kit Mutant Mice. Am J Hematol 2017. PubMed
  • Annaratone L, Simonetti M, Wernersson E, Marchiò C, Garnerone S, Scalzo MS, Bienko M, Chiarle R, Sapino A, Crosetto N. Quantification of HER2 and estrogen receptor heterogeneity in breast cancer by single-molecule RNA fluorescence in situ hybridization. 2017; 8:18680-18698. PubMed
  • Compagno M, Wang Q, Pighi C, Cheong TC, Meng FL, Poggio T, Yeap LS, Karaca E, Blasco RB, Langellotto F, Ambrogio C, Voena C, Wiestner A, Kasar SN, Brown JR, Sun J, Wu CJ, Gostissa M, Alt FW, Chiarle R. Phosphatidylinositol 3-kinase δ blockade increases genomic instability in B cells. Nature 2017; 542:489-493. PubMed
  • Griggio V, Mandili G, Vitale C, Capello M, Macor P, Serra S, Castella B, Peola S, Foglietta M, Drandi D, Omedé P, Sblattero D, Cappello P, Chiarle R, Deaglio S, Boccadoro M, Novelli F, Massaia M, Coscia M. Humoral immune responses toward tumor-derived antigens in previously untreated patients with chronic lymphocytic leukemia. 2016. PubMed
  • Bersani F, Lingua MF, Morena D, Foglizzo V, Miretti S, Lanzetti L, Carrà G, Morotti A, Ala U, Provero P, Chiarle R, Singer S, Ladanyi M, Tuschl T, Ponzetto C, Taulli R. Deep Sequencing Reveals a Novel miR-22 Regulatory Network with Therapeutic Potential in Rhabdomyosarcoma. Cancer Res 2016. PubMed
  • Voena C, Varesio LM, Zhang L, Menotti M, Poggio T, Panizza E, Wang Q, Minero VG, Fagoonee S, Compagno M, Altruda F, Monti S, Chiarle R. Oncogenic ALK regulates EMT in non-small cell lung carcinoma through repression of the epithelial splicing regulatory protein 1. 2016. PubMed
  • Choudhari R, Minero VG, Menotti M, Pulito R, Brakebusch C, Compagno M, Voena C, Ambrogio C, Chiarle R. Redundant and nonredundant roles for Cdc42 and Rac1 in lymphomas developed in NPM-ALK transgenic mice. Blood 2016; 127:1297-306. PubMed
  • Voena C, Chiarle R. Advances in cancer immunology and cancer immunotherapy. Discov Med 2016; 21:125-33. PubMed
  • Morena D, Maestro N, Bersani F, Forni PE, Lingua MF, Foglizzo V, Šćepanović P, Miretti S, Morotti A, Shern JF, Khan J, Ala U, Provero P, Sala V, Crepaldi T, Gasparini P, Casanova M, Ferrari A, Sozzi G, Chiarle R, Ponzetto C, Taulli R. Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes. Elife 2016. PubMed
  • Cheong TC, Compagno M, Chiarle R. Editing of mouse and human immunoglobulin genes by CRISPR-Cas9 system. Nat Commun 2016; 7:10934. PubMed
  • Voena C, Menotti M, Mastini C, Di Giacomo F, Longo DL, Castella B, Merlo ME, Ambrogio C, Wang Q, Minero VG, Poggio T, Martinengo C, D'Amico L, Panizza E, Mologni L, Cavallo F, Altruda F, Butaney M, Capelletti M, Inghirami G, Jänne PA, Chiarle R. Efficacy of a Cancer Vaccine against ALK-Rearranged Lung Tumors. Cancer Immunol Res 2015. PubMed
  • 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 Mdel C, 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. STAT3β 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 2008; 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