Dr Saverio Tardito - Oncometabolism

Introduction

Tardito head 2020 143

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.


For Plasmax™ cell culture medium, please visit www.cancertools.org

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

Read Trends in Molecular Medicine's article about Saverio's journey in science: Stories in Molecular Medicine


PubMed publications
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Lab Report

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Key Publications

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  F1000

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.

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

2022

Kay EJ, Paterson K, Riero-Domingo C, Sumpton D, Däbritz JHM, Tardito S, Boldrini C, Hernandez-Fernaud JR, Athineos D, Dhayade S, Stepanova E, Gjerga E, Neilson LJ, Lilla S, Hedley A, Koulouras G, McGregor G, Jamieson C, Johson RM, Park M, Kirschner K, Miller C, Kamphorst JJ, Loayza-Puch F, Saez-Rodriguez J, Mazzone M, Blyth K, Zagoni M, Zanivan S. Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix. Nature Metabolism. 2022;4(6):693-710.

Taurino G, Deshmukh R, Villar VH, Chiu M, Shaw R, Hedley A, Shokry E, Sumpton D, Dander E, D'Amico G, Bussolati O, Tardito S. Mesenchymal stromal cells cultured in physiological conditions sustain citrate secretion with glutamate anaplerosis. Mol Metab. 2022:101532.

Oberkersch RE, Pontarin G, Astone M, Spizzotin M, Arslanbaeva L, Tosi G, Panieri E, Ricciardi S, Allega MF, Brossa A, Grumati P, Bussolati B, Biffo S, Tardito S, Santoro MM. Aspartate metabolism in endothelial cells activates the mTORC1 pathway to initiate translation during angiogenesis. Developmental Cell. 2022;57:1241-1256

2021

Cano-Galiano A, Oudin A, Fack F, Allega MF, Sumpton D, Martinez-Garcia E, Dittmar G, Hau AC, De Falco A, Herold-Mende C, Bjerkvig R, Meiser J, Tardito S, Niclou SP. Cystathionine-γ-lyase drives antioxidant defense in cysteine-restricted IDH1-mutant astrocytomas. Neurooncol Adv. 2021;3:vdab057.

Chiu M, Taurino G, Dander E, Bardelli D, Fallati A, Andreoli R, Bianchi MG, Carubbi C, Pozzi G, Galuppo L, Mirandola P, Rizzari C, Tardito S, Biondi A, D'Amico G, Bussolati O. ALL blasts drive primary mesenchymal stromal cells to increase asparagine availability during asparaginase treatment. Blood Adv. 2021;5(23):5164-5178.

Gonzalez-Menendez P, Romano M, Yan H, Deshmukh R, Papoin J, Oburoglu L, Daumur M, Dumé AS, Phadke I, Mongellaz C, Qu X, Bories PN, Fontenay M, An X, Dardalhon V, Sitbon M, Zimmermann VS, Gallagher PG, Tardito S, Blanc L, Mohandas N, Taylor N, Kinet S. An IDH1-vitamin C crosstalk drives human erythroid development by inhibiting pro-oxidant mitochondrial metabolism. Cell Rep. 2021;34:108723. 

Matias MI, Yong CS, Foroushani A, Goldsmith C, Mongellaz C, Sezgin E, Levental KR, Talebi A, Perrault J, Riviere A, Dehairs J, Delos O, Bertand-Michel J, Portais JC, Wong M, Marie JC, Kelekar A, Kinet S, Zimmermann VS, Levental I, Yvan-Charvet L, Swinnen JV, Muljo SA, Hernandez-Vargas H, Tardito S, Taylor N, Dardalhon V. Regulatory T cell differentiation is controlled by alphaKG-induced alterations in mitochondrial metabolism and lipid homeostasis. Cell Rep. 2021;37:109911.

Najumudeen AK, Ceteci F, Fey SK, Hamm G, Steven RT, Hall H, Nikula CJ, Dexter A, Murta T, Race AM, Sumpton D, Vlahov N, Gay DM, Knight JRP, Jackstadt R, Leach JDG, Ridgway RA, Johnson ER, Nixon C, Hedley A, et al. The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer. Nat Genet. 2021;53:16-26.

Deshmukh R, Allega MF, Tardito S. A map of the altered glioma metabolism.  Trends Mol Med. 2021;

2020

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

2019

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.  F1000

2018

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).

2017

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.

2016

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

Lab Members

Tardito lab 022

Postdocotoral Scientists

Tobias Ackermann
Victor Villar

Scientific Officer

Ruhi Deshmukh

PhD student

Francesca Allega

Research

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Seminars

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