Dr Saverio Tardito - Oncometabolism
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.
Read The Atlantic's article on Saverio's work to improve cell culture media here: Scientists Have Been Studying Cancers in a Very Strange Way for Decades
Vande Voorde J, Ackermann T, Pfetzer N, Sumpton D, Mackay G, Kalna G, Nixon C, Blyth K, Gottlieb E, Tardito S. Improving the metabolic fidelity of cancer models with a physiological cell culture medium. Science Advances 2019; 5: eaau7314
Fack F*, Tardito S*, Hochart G*, Oudin A, Zheng L, Fritah S, Golebiewska A, Nazarov PV, Bernard A, Hau AC, Keunen O, Leenders W, Lund-Johansen M, Stauber J, Gottlieb E, Bjerkvig R, Niclou SP. Altered metabolic landscape in IDH-mutant gliomas affects phospholipid, energy, and oxidative stress pathways. EMBO Molecular Medicine. 2017; 9: 1681-1695 *Authors contributed equally.
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; 17:1513–1608.
Higlighted in: Rethinking glutamine addiction. Krall AS et al. Nat Cell Biol. 2015; 17: 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: 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: 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: 2561–7. *Authors contributed equally.
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
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
Hulme H, Meikle LM, Strittmatter N, van der Hooft JJJ, Swales J, Bragg RA, Villar VH, Ormsby MJ, Barnes S, Brown SL, Dexter A, Kamat MT, Komen JC, Walker D, Milling S, Osterweil EK, MacDonald AS, Schofield CJ, Tardito S, Bunch J, Douce G, Edgar JM, Edrada-Ebel R, Goodwin RJA, Burchmore R, Wall DM. Microbiome-derived carnitine mimics as previously unknown mediators of gut-brain axis communication. Science advances. 2020;6(11):eaax6328.
Patel R, Brzezinska EA, Repiscak P, Ahmad I, Mui E, Gao M, Blomme A, Harle V, Tan EH, Malviya G, Mrowinska A, Loveridge CJ, Rushworth LK, Edwards J, Ntala C, Nixon C, Hedley A, Mackay G, Tardito S, Sansom OJ, Leung HY. Activation of beta-catenin cooperates with loss of Pten to drive AR-independent castration-resistant prostate cancer. Cancer research. 2020; 80: 576–90
Ackermann T, Tardito S. Cell Culture Medium Formulation and Its Implications in Cancer Metabolism. Trends in cancer. 2019; 5: 329-332.
Clerc I, Moussa DA, Vahlas Z, Tardito S, Oburoglu L, Hope TJ, Sitbon M, Dardalhon V, Mongellaz C, Taylor N. Entry of glucose- and glutamine-derived carbons into the citric acid cycle supports early steps of HIV-1 infection in CD4 T cells. Nat Metab. 2019; 1: 717-730.
Vande Voorde J, Ackermann T, Pfetzer N, Sumpton D, Mackay G, Kalna G, Nixon C, Blyth K, Gottlieb E, Tardito S. Improving the metabolic fidelity of cancer models with a physiological cell culture medium Science Advances 2019; 5: eaau7314.
Chiu M, Taurino G, Bianchi MG, Ottaviani L, Andreoli R, Ciociola T, Lagrasta CAM, Tardito S, Bussolati O. Oligodendroglioma Cells Lack Glutamine Synthetase and Are Auxotrophic for Glutamine, but Do not Depend on Glutamine Anaplerosis for Growth. Int J Mol Sci 2018; 19 (4).
Fack F, Tardito S, Hochart G, Oudin A, Zheng L, Fritah S, Golebiewska A, Nazarov PV, Bernard A, Hau AC, Keunen O, Leenders W, Lund-Johansen M, Stauber J, Gottlieb E, Bjerkvig R, Niclou SP.
Altered metabolic landscape in IDH-mutant gliomas affects phospholipid, energy, and oxidative stress pathways. EMBO Mol Med 2017; 9: 1681–95.
Kuntz EM, Baquero P, Michie AM, Dunn K, Tardito S, Holyoake TL, Helgason GV, Gottlieb E. Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemia stem cells. Nat Med 2017 23: 1234–40.
Vazquez A, Kamphorst JJ, Markert EK, Schug Z, Tardito S, Gottlieb E. Cancer Metabolism at a Glance. Journal of Cell Science. 2016;