Introduction
 As a result of increased bioenergetic demands and the need to grow and proliferate faster, cancer cells have unique metabolic traits compared to normal cells.
At the same time, cancer cells are exposed to more extreme conditions of metabolic stress due to the uncontrolled growth of the tumour away from the vascular system that provides oxygen and nutrients to its cells. Therefore, cancer cells have developed defence mechanisms that are selected under conditions of stress and cells that survive this strongly selective environment have a more aggressive phenotype.
Targeting these survival mechanisms may help eliminate cancer growth and specifically induce cancer cell death.
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Lab Report
 Scientific Report 2010 Gottlieb (285.78 kB)
Key PublicationsFrezza C, Zheng L, Folger O, Rajagopalan KN, Mackenzie ED, Jerby L, Micaroni M, Chaneton B, Adam J, Hedley A, Kalna G, Tomlinson IP, Pollard PJ, Watson DG, Deberardinis RJ, Shlomi T, Ruppin E, Gottlieb E (2011). Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature 2011 Aug 17. doi: 10.1038/nature10363. [Epub ahead of print]
Tennant DA, Frezza C, Mackenzie ED, Nguyen QD, Zheng L, Selak MA, Roberts DL, Dive C, Watson DG, Aboagye EO, Gottlieb E (2009).
Reactivating HIF prolyl hydroxylases under hypoxia results in metabolic catastrophe and cell death. Oncogene 28, 4009-21.
Gonzalvez F, Schug ZT, Houtkooper RH, MacKenzie ED, Brooks DG, Wanders RJ, Petit PX, Vaz FM, Gottlieb E (2008). Cardiolipin provides an essential activating platform for caspase-8 on mitochondria. J Cell Biol. 183, 681-96.
MacKenzie ED, Selak MA, Tennant DA, Payne LJ, Crosby S, Frederiksen CM, Watson DG, Gottlieb E. (2007). Cell-permeating α-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells. Mol. Cell. Biol. 27, 3282-3289.
Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nadano K, Bartrons R, Gottlieb E, Vousden, KH. (2006). TIGAR, a novel regulator of glycolysis and apoptosis, is induced by p53. Cell 126, 107-120.
Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD, Yi P, Simon MC, Thompson CB, Gottlieb E (2005). Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase. Cancer Cell 7, 77-85.
Biography
Education and qualifications
1999: PhD, Weizmann Institute of Science, Israel, Supervisor Moshe Oren
1992: MSc, Weizmann Institute of Science, Israel, Supervisor Moshe Oren
1990: BSc, Hebrew University, Israel
Appointments
2003-present: Group Leader, Beatson Institute for Cancer Research, Glasgow
2009-present: Professor, University of Glasgow
2007-2009: Reader, University of Glasgow
1999-2003: Postdoctoral Fellow with Craig Thompson, University of Pennsylvania, Philadelphia, USA
1998-1999: Postdoctoral Fellow with Craig Thompson, University of Chicago, USA
Honours and awards
Leukemia and Lymphoma Society Special Fellowship, 2001
EMBO Long-Term Fellowship, 1998
Recent Publications
2011
Frezza C, Zheng L, Folger O, Rajagopalan KN, Mackenzie ED, Jerby L, Micaroni M, Chaneton B, Adam J, Hedley A, Kalna G, Tomlinson IP, Pollard PJ, Watson DG, Deberardinis RJ, Shlomi T, Ruppin E, Gottlieb E (2011). Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature 2011 Aug 17. doi: 10.1038/nature10363. [Epub ahead of print]
Gottlieb E (2011). p53 guards the metabolic pathway less travelled. Nat Cell Biol. 13, 195-7.
Frezza C, Pollard PJ, Gottlieb E (2011). Inborn and acquired metabolic defects in cancer. J Mol Med. 89, 213-20.
Folger O, Jerby L, Frezza C, Gottlieb E, Ruppin E, Shlomi T (2011). Predicting selective drug targets in cancer through metabolic networks. Mol Syst Biol. 7, 517.
Shlomi T, Benyamini T, Gottlieb E, Sharan R, Ruppin E (2011). Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect. PLoS Comput Biol 7, e1002018.
2010
Schug ZT, Gonzalvez F, Houtkooper RH, Vaz FM,
Gottlieb E (2010).
BID is cleaved by caspase-8 within a native complex
on the mitochondrial membrane. Cell Death Differ. 18, 538-48.
Tennant DA, Gottlieb E (2010). HIF prolyl hydroxylase-3 mediates alpha-ketoglutarate-induced apoptosis and tumor suppression. J Mol Med. 88, 839-49.
Tennant DA, Duran RV, Gottlieb E (2010). Targeting metabolic transformation for cancer therapy. Nat Rev Cancer 10, 267-77.
2009
Tennant DA, Frezza C, Mackenzie ED, Nguyen QD, Zheng L, Selak MA, Roberts DL, Dive C, Watson DG, Aboagye EO, Gottlieb E (2009).
Reactivating HIF prolyl hydroxylases under hypoxia results in metabolic catastrophe and cell death. Oncogene 28, 4009-21.
Boulahbel H, Duran RV, Gottlieb E (2009). Prolyl hydroxylases as regulators of cell metabolism. Biochem Soc Trans. 37, 291-4.
Frezza C, Gottlieb E (2009). Mitochondria in Cancer: Not just innocent bystanders. Seminars in Cancer Biology 19, 4-11.
Gottlieb E (2009). Cancer: The fat and the furious. Nature 461, 44-5.
King A, Gottlieb E (2009). Glucose metabolism and programmed cell death: an evolutionary and mechanistic perspective. Curr Opin
Cell Biol. 21, 885-93.
Schug ZT, Gottlieb E (2009). Cardiolipin acts as a mitochondrial signalling platform to launch apoptosis. Biochim Biophys Acta 1788, 2022-31.
Tennant DA, Duran RV, Boulahbel H, Gottlieb E (2009). Metabolic transformation in cancer. Carcinogenesis 30, 1269-80.
2008
Gonzalvez F, Schug ZT, Houtkooper RH, MacKenzie ED, Brooks DG, Wanders RJ, Petit PX, Vaz FM, Gottlieb E (2008). Cardiolipin provides an essential activating platform for caspase-8 on mitochondria. J Cell Biol. 183, 681-96.
2007
Gonzalvez F, Gottlieb (2007). Cardiolipin: setting the beat of apoptosis. Apoptosis 12, 877-885.
MacKenzie ED, Selak MA, Tennant DA, Payne LJ, Crosby S, Frederiksen CM, Watson DG, Gottlieb E. (2007). Cell-permeating α-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells. Mol. Cell. Biol. 27, 3282-3289.
Images
Studying mitochondrial structure using a scanning electron microscope.
Mitochondria were purified by Francois Gonzalvez (a former student in
the lab) and the image was taken by Prof. Terry Allen from the Paterson
Institute for Cancer Research in Manchester.
Lab Members
Post-docs: Christian Frezza, Zach Schug, Dan Tennant, Leon Zheng
Scientific Officer: Elaine MacKenzie
PhD Students: Barbara Chaneton, Laura Galbraith, Lisa Heiserich
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