Coordinator of Research Team
Persio DELLO SBARBA (associate professor of General Pathology)
Metabolic characterization of leukaemia stem cell subsets & cancer cell signaling
office telephone number: +390552751293
Brief biographical sketch of the Coordinator
born in Pisa in 1953;
1979 Doctor in Medicine & Surgery, Università di Firenze;
1982 Post-doctoral diploma in Clinical Immunology and Allergology, Università di Firenze;
1988 PhD in Experimental Pathology, Università di Firenze;
1987-1990 Research Associate at the Department of Microbiology and Immunology, later Department of Developmental Biology and Cancer, Albert Einstein College of Medicine, New York City;
1995 Visiting scientist at the Institut für Mikrobiologie und Genetik, Wiener Biozentrum, Universität Wien.
Member of the scientific board of the
Regional Ph.D. Programme (Tuscany) in “Genetics, Oncology and Clinical Medicine” (administrative support c/o Università degli Studi di Siena).
Current / past member of the following Scientific Societies:
New York Academy of Sciences
International Society for Cancer Metabolism (ISCaM)
International Society for Experimental Hematology (ISEH)
Società Italiana di Patologia e Medicina Translazionale (SIPMeT)
Società Italiana di Ematologia Sperimentale (SIES)
Società Italiana di Cancerologia (SIC)
British Society for Immunology (BSI)
Società Italiana di Immunologia
Member of the editorial board of the following Journals:
Associate Editor of the journal “Public Library of Sciences (PLoS)-One”.
1) Maria Grazia CIPOLLESCHI, M.D. (1954), tenure assistant professor
2) Elisabetta ROVIDA, Ph.D. (1970) assistant professor
3) Matteo LULLI, Ph.D. (1978) senior post-doctoral fellow
4) Ignazia TUSA, Ph.D. (1983) post-doctoral fellow
5) Alessandro TUBITA, Ph.D. student (1984)
6) Martina POTETI, Ph.D. student (1988)
Current research interests
(A) metabolic control of the maintenance of stem and progenitor cells in chronic myeloid leukaemia (CML) and other leukaemias;
(B) use of oxygen and nutrient restriction to select CML stem cells as a tool to test their drug sensitivity;
(C) MAPK (Mitogen-Activated Protein Kinases) signaling in cells of leukaemias and solid neoplasias.
Current / recent sources of funding
2015-2018 (3-year grant)
2013-2015 (3-year grant)
Istituto Toscano Tumori (ITT)
Associazione Italiana per la Ricerca sul Cancro (AIRC)
2011-2013 (3-year grant)
Regione Toscana – Regional Programme “Health 2009”
2010-2012 (2-year grant)
Ministero della Salute – Ricerca Finalizzata 2008
2009-2011 (3-year grant)
2008-2010 (2-year grant)
10 best publications of the last 5 years
1) Cheloni G, Tanturli M, Tusa I, DeSouza NH, Shan Y, Gozzini A, Mazurier F, Rovida E, Li S, Dello Sbarba P. Targeting Chronic Myeloid Leukemia Stem Cells with the Hypoxia-Inducible Factor Inhibitor Acriflavine. Blood 2017 (in press).
2) Cipolleschi MG, Marzi I, Rovida E, Olivotto M, Dello Sbarba P. Low-dose methotrexate enhances cycling of highly anaplastic cancer cells. Cell Cycle 16:280-5, 2017.
3) Bono S, Lulli M, D'Agostino VG, Di Gesualdo F, Loffredo R, Cipolleschi MG, Provenzani A, Rovida E, Dello Sbarba P. Different BCR/Abl protein suppression patterns as a converging trait of chronic myeloid leukemia cell adaptation to energy restriction. Oncotarget 7:84810-25, 2016.
4) Del Poggetto E, Tanturli M, Ben-Califa N, Gozzini A, Tusa I, Cheloni G, Marzi I, Cipolleschi MG, Kashman Y, Neumann D, Rovida E, Dello Sbarba P. Salarin C inhibits the maintenance of chronic myeloid leukemia progenitor cells. Cell Cycle 14:3146-54, 2015.
5) Digiacomo G, Ziche M, Dello Sbarba P, Donnini S, Rovida E. Prostaglandin E2 transactivates the colony-stimulating factor-1 receptor and synergizes with colony-stimulating factor-1 in the induction of macrophage migration via the mitogen-activated protein kinase ERK1/2. FASEB J 29:2545-54, 2015.
6) Rovida E, Di Maira G, Tusa I, Cannito S, Paternostro C, Navari N, Vivoli E, Deng X, Gray NS, Esparís-Ogando A, David E, Pandiella A, Dello Sbarba P, Parola M, Marra F. The mitogen-activated protein kinase ERK5 regulates the development and growth of hepatocellular carcinoma. Gut 64:1454-65, 2015.
7) Rovida E, Peppicelli S, Bono S, Bianchini F, Tusa I, Cheloni G, Marzi I, Cipolleschi MG, Calorini L, Dello Sbarba P. The metabolically-modulated stem cell niche: a dynamic scenario regulating cancer cell phenotype and resistance to therapy. Cell Cycle 13:3169-75, 2014.
8) Cipolleschi MG, Marzi I, Santini R, Fredducci D, Vinci MC, D'Amico M, Rovida E, Stivarou T, Torre E, Dello Sbarba P, Stecca B, Olivotto M. Hypoxia-resistant profile implies vulnerability of cancer stem cells to physiological agents, which suggests new therapeutic targets. Cell Cycle 13:268-78, 2014.
9) Barbetti V, Morandi A, Tusa I, Digiacomo G, Riverso M, Marzi I., Cipolleschi M.G., Bessi S, Giannini A, Di Leo A, Dello Sbarba P, Rovida E. Chromatin-associated CSF-1R binds to the promoter of proliferation-related genes in breast cancer cells. Oncogene 33:4359-64, 2014.
10) Barbetti V., Tusa I., Cipolleschi M.G., Rovida E., Dello Sbarba P. AML1/ETO sensitizes via TRAIL acute myeloid leukemia cells to the pro-apoptotic effects of hypoxia. Cell Death and Disease 4:e536; doi: 10.1038/cddis.2013.49, 2013.
Previous research experiences
(A) down-modulation of the Macrophage Colony-Stimulating Factor (M-CSF) receptor in the course of macrophage activation;
(B) M-CSF and MAPK (Mitogen-Activated Protein Kinases) signalling in mesenchymal and cancer cells;
(C) epigenetical mechanisms as a target for the treatment of acute myeloid leukaemias.
Main scientific contributions
In the field of normal haematopoiesis, we showed that incubation in low oxygen enhances the maintenance in vitro of haematopoietic stem cells (HSC), but not progenitor cells, and inhibits HSC commitment to clonal expansion. These breakthrough findings led us to be the first to hypothesize the existence of "hypoxic stem cell niches" in vivo (Blood 82:2031, 1993). We later demonstrated that HSC are capable to cycle in low oxygen, a rather unexpected finding (Leukemia 14:735, 2000) and, even more interesting, that low oxygen steers HSC cycling towards self-renewal and HSC maintenance, thus antagonizing clonal expansion (Experimental Hematology 30:67, 2002).
In the field of leukaemias, we demonstrated that leukaemia cell lines are functionally heterogeneous and comprise cell subsets endowed with different stem/progenitor cell potential (Stem Cells 25:1119, 2007). With another breakthrough study, we showed that the stem cell potential of chronic myeloid leukaemia (CML) cell populations is maintained in very low oxygen, where the oncogenetic BCR/Abl protein is reversibly suppressed. Consequently, LSC adapted to the stem cell niches are independent of BCR/Abl signalling and refractory to the BCR/Abl-targeting tyrosine kinase inhibitors (TKi) used for CML therapy (Leukemia 20:1291, 2006). These findings led us to predict that even next-generation TKi would be unable to suppress LSC responsible for relapse of disease. This prediction is increasingly confirmed correct. These studies identified a novel mechanism of TKi resistance and provided a mechanistic background to the therapeutic targeting of BCR/Ablprotein-negative LSC. We later showed that glucose shortage is relevant to BCR/Abl protein suppression in low oxygen (Haematologica 96:204, 2011), which led us to put forward the innovative hypothesis of a “dual” CML stem cell niche characterized by the homing of BCR/Ablprotein-positive LSC in the low-oxygen niche periphery and of BCR/Ablprotein-negative LSC in the low-glucose niche core (Cell Cycle 13:3169, 2014). Finally, we recently characterized the mechanisms of BCR/Abl protein suppression under oxygen and/or glucose shortage (Oncotarget 7:84810, 2016) and proposed an innovative strategy capable to suppress LSC of CML refractory to current therapeutic approach (Blood 2017, in press).
Dr. Angelo di Leo, Medical Oncology Unit, ASL 4, Prato;
Dr. Barbara Stecca and Dr. Mario Chiariello, ITT Core Research Laboratories;
Dr. Nathanael Gray, Dana Farber Cancer Institute, Harvard Medical School, Boston (MA; U.S.A.);
Dr. Nathalie Mazure, UMR CNRS 7284 INSERM U1081 UNS, Université de Nice Sophia-Antipolis;
Dr. Atanasio Pandiella, Centro de Investigation del Cancer (CIC), Universitad de Salamanca;
Prof. Shaoguang Li, University of Massachusetts Medical School, Department of Medicine, Division of Hematology/Oncology, Worcester (MA; U.S.A.);
Prof. Vincent Praloran, Laboratoire d'Hématopoïèse Normale et Pathologique (Unité CNRS 2617), Université Victor Segalen-Bordeaux-2, Bordeaux;
Prof. Zoran Ivanović, Etablissement Français du Sang Aquitaine-Limousin, Bordeaux.