Saverio Tardito - Oncometabolism

Introduction

TarditoS

At the foundation of cellular and tissue growth stands transfer of chemical energy from nutrients into macromolecules. Tumours are no exception to this principle, and unavoidably seek metabolic states that support anabolism and growth.

Our vision is that the tissue of origin influences the biochemical pathways utilized by tumours to grow in two ways. On the one hand by imposing environmental constraints, the tissue of origin exposes metabolic vulnerabilities of the tumour. On the other hand, enzymes normally restricted to a defined population of differentiated cells, and required for tissue physiological functions, can be hijacked by cancer cells to enhance their metabolic fitness. These concepts apply for instance to glutamine and glutamate. These amino acids are instrumental to physiological processes, such as neurotransmission in brain, and ammonia homeostasis in liver, but are at the same time obligate substrates for anabolism of glioma and hepatocellular carcinoma.

If cancer cells divert specific nutrients towards anabolism, or hijack physiological processes to gain a selective advantage, therapeutic targets which spare organ functions while interfering with tumour growth, await to be discovered by our research.

Current Vacancies

Postdoctoral Research Scientist

Senior Scientific Officer


PubMed publications

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Lab Report

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Key Publications

Tardito S, Oudin A, Ahmed SU, Fack F, Keunen O, Zheng L, Miletic H, Sakariassen PO, Weinstock A, Wagner A, Lindsay SL, Hock AK, Barnett SC, Ruppin E, Mørkve SH, Lund–Johansen M, Chalmers AJ, Bjerkvig R, Simone P, Gottlieb E. Glutamine Synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma. Nature Cell Biology. 2015; 17(12):1513–1608.
Higlighted in: Rethinking glutamine addiction. Krall AS et al. Nat Cell Biol. 2015;17(12):1515-7 & War on Glioblastoma Multiforme: 2-Pronged Siege on Glutamine. Panchanathan RS et al. World Neurosurg 2016;91:254-6.

Chiu M*, Tardito S*, Pillozzi S, Arcangeli A, Armento A, Uggeri J, Missale G, Bianchi MG, Barilli A, Dall'Asta V, Campanini N, Silini EM, Fuchs J, Armeanu–Ebinger S, Bussolati O. Glutamine depletion by crisantaspase hinders the growth of human hepatocellular carcinoma xenografts. British Journal of Cancer. 2014;111(6):1159–67. *Authors contributed equally.

Oburoglu L, Tardito S*, Fritz V*, de Barros SC*, Merida P*, Craveiro M, Mamede J, Cretenet G, Mongellaz C, An X, Klysz D, Touhami J, Boyer–Clavel M, Battini JL, Dardalhon V, Zimmermann VS, Mohandas N, Gottlieb E, Sitbon M, Kinet S, Taylor N. Glucose and glutamine metabolism regulate human hematopoietic stem cell lineage specification. Cell Stem Cell. 2014;15(2):169–84. *Authors contributed equally.

Chiu M*, Tardito S*, Barilli A, Bianchi MG, Dall'Asta V, Bussolati O. Glutamine stimulates mTORC1 independent of the cell content of essential amino acids. Amino Acids. 2012; 43(6):2561–7. *Authors contributed equally.

Tardito S, Chiu M, Franchi–Gazzola R, Dall'Asta V, Comi P, Bussolati O. The non–proteinogenic amino acids L–methionine sulfoximine and DL–phosphinothricin activate mTOR. Amino Acids. 2012; 42(6):2507–12.

Tardito S, Chiu M, Uggeri J, Zerbini A, Da Ros F, Dall'Asta V, Missale G, Bussolati O. L–Asparaginase and inhibitors of glutamine synthetase disclose glutamine addiction of β–catenin–mutated human hepatocellular carcinoma cells. Current Cancer Drug Targets. 2011; 11(8):929–43.

Biography

Education and qualifications

2008: PhD, Molecular Biology and Pathology, University of Parma, Italy, Supervisors Renata Franchi–Gazzola and Ovidio Bussolati
2003: BS/MS, Biology, University of Parma, Italy

Appointments

Sep 2016-present: Junior Group Leader, CRUK Beatson Institute, Glasgow
2011-2016: Postdoctoral Fellow with Eyal Gottlieb, CRUK Beatson Institute, Glasgow
Feb/Mar 2015: Visiting Research Fellow with Simone Niclou, Department of Oncology, Luxembourg Institute of Health
2010-2011: Postdoctoral Fellow with Ovidio Bussolati, University of Parma, Italy
2009-2010: Postdoctoral Fellow with Luciano Marchió, University of Parma, Italy
2008-2009: Postdoctoral Fellow with Ian De Belle, Laval University, Quebec City, Canada

Honours and awards

AIRC–Marie Curie International Fellowship in Cancer Research, 2011
Government of Canada Post–Doctoral Research Fellowship, 2008
Inter–University Consortium for Research in Metal Chemistry of Biological Systems Research Fellowship, 2007
Oreste Battioni Award from Lega Italiana Lotta contro i Tumori, 2004

Recent Publications

2016

Vazquez A, Kamphorst JJ, Markert EK, Schug Z, Tardito S, Gottlieb E. Cancer Metabolism at a Glance. Journal of Cell Science. 2016; Accepted for publication.

2015

Tardito S, Oudin A, Ahmed SU, Fack F, Keunen O, Zheng L, Miletic H, Sakariassen PO, Weinstock A, Wagner A, Lindsay SL, Hock AK, Barnett SC, Ruppin E, Mørkve SH, Lund–Johansen M, Chalmers AJ, Bjerkvig R, Simone P, Gottlieb E. Glutamine Synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma. Nature Cell Biology. 2015; 17(12):1513–1608.

Schug ZT, Peck B, Jones DT, Zhang Q, Grosskurth S, Alam IS, Goodwin LM, Smethurst E, Mason S, Blyth K, McGarry L, James D, Shanks E, Kalna G, Saunders RE, Jiang M, Howell M, Lassailly F, Thin MZ, Spencer–Dene B, Stamp G, van den Broek NJ, Mackay G, Bulusu V, Kamphorst JJ, Tardito S, Strachan D, Harris AL, Aboagye EO, Critchlow SE, Wakelam MJ, Schulze A, Gottlieb E. Acetyl–CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer Cell. 2015;27(1):57–71.

2014

Chiu M*, Tardito S*, Pillozzi S, Arcangeli A, Armento A, Uggeri J, Missale G, Bianchi MG, Barilli A, Dall'Asta V, Campanini N, Silini EM, Fuchs J, Armeanu–Ebinger S, Bussolati O. Glutamine depletion by crisantaspase hinders the growth of human hepatocellular carcinoma xenografts. British Journal of Cancer. 2014;111(6):1159–67. *Authors contributed equally.

Oburoglu L, Tardito S*, Fritz V*, de Barros SC*, Merida P*, Craveiro M, Mamede J, Cretenet G, Mongellaz C, An X, Klysz D, Touhami J, Boyer–Clavel M, Battini JL, Dardalhon V, Zimmermann VS, Mohandas N, Gottlieb E, Sitbon M, Kinet S, Taylor N. Glucose and glutamine metabolism regulate human hematopoietic stem cell lineage specification. Cell Stem Cell. 2014;15(2):169–84. *Authors contributed equally.

Rizzi F, Naponelli V, Silva A, Modernelli A, Ramazzina I, Bonacini M, Tardito S, Gatti R, Uggeri J, Bettuzzi S. Polyphenon E(R), a standardized green tea extract, induces endoplasmic reticulum stress, leading to death of immortalized PNT1a cells by anoikis and tumorigenic PC3 by necroptosis. Carcinogenesis. 2014; 35(4):828–39.

2013

Durán RV, MacKenzie ED, Boulahbel H, Frezza C, Heiserich L, Tardito S, Bussolati O, Rocha S, Hall MN, Gottlieb E. HIF–independent role of prolyl hydroxylases in the cellular response to amino acids. Oncogene. 2013; 32(38):4549–56.

2012

Tardito S*, Barilli A*, Bassanetti I, Tegoni M, Bussolati O, Franchi–Gazzola R, Mucchino C, Marchiò L. Copper–dependent cytotoxicity of 8–hydroxyquinoline derivatives correlates with their hydrophobicity and does not require caspase activation. Journal of Medicinal Chemistry. 2012; 55(23):10448–59. *Authors contributed equally.

Chiu M*, Tardito S*, Barilli A, Bianchi MG, Dall'Asta V, Bussolati O. Glutamine stimulates mTORC1 independent of the cell content of essential amino acids. Amino Acids. 2012; 43(6):2561–7. *Authors contributed equally.

Tardito S, Chiu M, Franchi–Gazzola R, Dall'Asta V, Comi P, Bussolati O. The non–proteinogenic amino acids L–methionine sulfoximine and DL–phosphinothricin activate mTOR. Amino Acids. 2012; 42(6):2507–12.

Covini D, Tardito S, Bussolati O, Chiarelli LR, Pasquetto MV, Digilio R, Valentini G, Scotti C. Expanding targets for a metabolic therapy of cancer: L–asparaginase. Recent Patents on Anti–Cancer Drug Discovery. 2012; 7(1):4–13.

Lab Members

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Post-doc

Victor Villar

Research

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