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Roberto  Chiarle, MD

Roberto Chiarle, MD
Lab:
Chiarle Laboratory
Department:
Pathology Research
Hospital Title:
Research Associate
Academic Title:
Associate Professor of Pathology, Harvard Medical School
Research Focus Area:
Genetics and chromosomal translocations in lymphoma and other cancers
Contact:
617-919-2662
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Research Overview

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My laboratory is interested in mechanisms and therapy of cancers. One main focus of the lab is to elucidate the mechanisms that drive transformation of lymphocytes. Most lymphomas, but also an increasing number of solid tumors, are characterized by defined oncogenic events, such as chromosomal translocations. One line of research in the lab is dedicated to the elucidation of basic principles that govern chromosomal translocation formation in normal and neoplastic cells. In collaboration with other groups, 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), tissue specificity and other nuclear or DNA repair factors can influence the type and the frequency of translocations found in human cancers. Among disease-defining translocation 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 by discovering multiple pathways exploited 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-specific 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. 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 role of such gene in normal B cell development and lymphoma formation.

About Roberto Chiarle

Roberto Chiarle received an M.D. degree from the University of Turin, Italy. Then, he earned a Board in Surgical Pathology from the University of Torino. He did his postdoc research training with Giorgio Inghirami and Michele Pagano at the New York University, where he worked on the molecular pathogenesis of B and T cell lymphomas. He was appointed as Assistant Professor in Pathology and as Attending Physician in Pathology in the University of Turin, Italy in 1999, then promoted to Associate Professor in 2006. In Italy, he started his own lab and worked on the ALK oncogene in human lymphoma, to discover new molecular mechanisms of ALK mediated cell transformation and new ALK specific therapies. From 2008 to 2010, he was Visiting Professor in Pathology in Fred W. Alt lab at the Immune Disease Institute/Children’s Hospital, Boston, where he worked on chromosomal translocations and contributed to develop a new high-throughput method to clone translocations genome-wide from primary B cells. In 2012, he was appointed as Associate Professor of Pathology at Harvard Medical School and started his own lab at the Children’s Hospital Boston. He won numerous grants and awards in Europe, such as the Italian National “Premio Sapio” Junior Investigator Award, the Italian National prize “Carlo Chianello” Foundation Research Award, the prestigious ERC Starting Grant from the European Research Council and the research award from the Association for International Cancer Research, UK.

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