In vivo models of ALK-driven tumors
and ALK-targeted immunotherapy

Group Leader:
Roberto Chiarle, M.D.

Group Members:
Claudia Voena, Ph.D.
Mara Compagno. Ph.D.
Cristina Mastini, Ph.D.
Silvia Peola, Lab manager
Valerio Minero, Ph.D.
Matteo Menotti, Ph.D. student
Teresa Poggio, M.S.
Lydia Varesio, M.S.
Maria Stella Scalzo, technician

Contact:
Department of Molecular Biotechnology and Health Sciences
University of Torino
Via Santena, 7 - 10126 Torino, ITALY
Tel: +39 011.633.6861
Fax: +39 011.633.6887

Afiliation:
Department of Pathology, Children's Hospital Boston and Harvard Medical School, USA

Funding:
FP7 ERC-2009-StG grant (proposal no. 242965 "Lunely")
ERC –PoC 2012 N° 324621 "ALKVAX"
AIRC IG-12023 grant
AICR 12-0216 grant

Description:
Major projects in the laboratory are:
- understanding the molecular mechanisms of ALK-driven transformation with in vitro and in vivo models
- understanding the molecular mechanisms leading to ALK-translocation in different tissues
- therapeutic targeting of ALK by means of specific inhibitors, drugs and immunotherapy

Collaborators:
Dr. Carlo Gambacorti-Passerini (Monza, Italy)
Dr. Giorgio Inghirami (New York, USA)
Dr. Suzanne Turner (Cambridge, UK)
Dr. Lukas Kenner (Vienna, Austria)
Dr. Lara Mussolin (Padova, Italy)

Publications:
1. Duan S, Cermak L, Pagan J, Rossi M, Martinengo C, Francia di Celle P, Chapuy B, Shipp M, Chiarle R*, and Pagano M*. FBXO11 targets BCL6 for degradation and is inactivated in Diffuse Large B-Cell Lymphomas. Nature 2012 Jan 5;481(7379):90-3. *Corresponding Authors.
2. Chiarle R, Zhang Y, Frock RL, Lewis SM, Molinie B, Ho Y, Myers DR, Choi VW, Compagno M, Malkin DJ, Neuberg D, Monti S, Giallourakis CC, Gostissa M, and Alt FW. Genome-Wide Translocation Sequencing Reveals Mechanisms of Chromosome Breaks and Rearrangements in B Cells. Cell 2011 Sep 30;147(1):107-19. Highlighted on the Cell cover and in Cell 2011 Sep 30;147(1):20-2 and in Nature Review Genetics 2011 Nov;12(11):741.
3. Chiarle R, Voena C, Ambrogio C, Piva R, Inghirami G. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nature Review Cancer 2008 Jan;8(1):11-23. Highlighted on the Nat Rev Cancer cover.
4. 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. Nature Medicine 2008 Jun;14(6):676-80.
5. Chiarle R, Simmons WJ, Cai H, Dhall G, Zamò A, Raz R, Karras J, Levy DE , Inghirami G. Stat3 is required for ALK-mediated lymphomagenesis and provides a possible therapeutic target. Nature Medicine 2005;11(6): 623-629. Highlighted in Nature Medicine 2005 Jun;11(6):595-6.

Weblinks:
http://chiarle.tch.harvard.edu/content/ItalyLab
http://chiarle.tch.harvard.edu/content/roberto-chiarle-md
http://www.lunely.unito.it

Tools: We have mouse models for ALK-rearranged lymphoma and NSCLC. We have a variety of human and murine ALK-positive cell lines

Techniques: We know several technicques in vivo for mouse experiments as well as several molecular biology techniques