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      Eyal Gottlieb Image

      Eyal Gottlieb, MBA, PhD

      Department of Cancer Biology, Division of Discovery Science

      About Dr. Eyal Gottlieb

      My research focuses on unraveling the metabolic control of cancer, aiming to elucidate physiological and pathological metabolic changes that regulate cell fate and inform new therapeutic strategies. Employing interdisciplinary methods—including metabolomics, clinical, and pre-clinical models—I investigate molecular mechanisms, biomarkers, and therapeutic opportunities in cancer and other metabolic disorders.


      I earned my PhD in Cancer Biology at the Weizmann Institute, where I uncovered the pathophysiological role of p53 in cell death. My postdoctoral training included an EMBO fellowship at the University of Chicago and a Leukemia and Lymphoma Society Special Fellowship at the University of Pennsylvania, where I developed a deep interest in cancer metabolism. I launched my independent research career in 2003 at the Cancer Research UK Beatson Institute and later transitioned to the Technion–Israel Institute of Technology, where I led the Rappaport Institute for Research in the Medical Sciences. In January 2023, I joined the University of Texas MD Anderson Cancer Center as Vice President for Research and Professor in the Department of Cancer Biology.


      Throughout my career, I have made significant contributions to cancer metabolism research. Key discoveries include the identification of onco-metabolic signaling cascades linked to the inactivation of tumor suppressors and TCA cycle enzymes, such as succinate dehydrogenase (SDH) and fumarate hydratase (FH). These findings revealed that TCA cycle metabolites signal from mitochondria to the cytosol and nucleus, inhibiting α-ketoglutarate-dependent dioxygenases and hence perturbing HIF degradation, and histone/DNA demethylation. Additionally, my research has defined metabolic vulnerabilities in FH- and SDH-deficient cells, uncovering novel therapeutic opportunities.


      My work has also explored metabolic stress adaptations in cancer, demonstrating the essential role of acetate as a carbon source under stress conditions and validating ACSS2 as a therapeutic target. Leveraging metabolomics, I identified plasma biomarkers that reliably diagnose FH-deficient renal cell carcinoma. In metabolic dysfunction-associated steatotic liver disease (MASLD), I discovered that accelerated serine synthesis via reversed SHMT2 activity leads to glycine depletion, glutathione deficiency, and heightened xenobiotic sensitivity in hepatic steatosis.


      These discoveries collectively advance our understanding of cancer metabolism and offer promising avenues for clinical translation.


      Read More

      Present Title & Affiliation

      Primary Appointment

      Vice President, Research, The University of Texas MD Anderson Cancer Center, Houston, Texas

      Professor and R.E. Bob Smith Distinguished Chair in Cancer Biology, Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas

      Education & Training

      Degree-Granting Education

      1998Weizmann Institute of Science, IL, PhD, Molecular Cell Biology
      1993Weizmann Institute of Science, IL, MSc, Molecular Cell Biology
      2020Technion – Israel Institute of Technology, IL, MBA, Faculty of Industrial Engineering and Management
      1990The Hebrew University of Jerusalem, IL, BSc, Agriculture (Animal Sciences)

      Postgraduate Training

      1999-2003Postgraduate Fellow, University of Pennsylvania, Pennsylvania, PA
      1998-1999Postgraduate Fellow, University of Chicago, Chicago, IL

      Experience & Service

      Faculty Academic Appointments

      Professor, Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, 2016 - 2022

      Senior Research Group leader, Cancer Research UK, Beatson Institute, Glasgow, 2009 - 2018

      Professor of Molecular Cell Biology, University of Glasgow, Glasgow, 2009 - 2018

      Research Group Leader, Cancer Research UK, Beatson Institute, Glasgow, 2003 - 2009

      Extramural Institutional Committee Activities

      Member, Scientific Evaluation Committee, German Center for Cancer Research (DKFZ); Helmholtz Association, 2025

      Member, Scientific Advisory Board, German Cancer Center (DKFZ), 2023

      Member, Scientific Advisory Board, Vesalius Research Center (VRC) - Vlaams Institute of Biotechnology (VIB), 2020

      Member, Scientific Advisory Board, Department of Oncology, Catholic University of Leuven, 2017

      member, Scientific Advisory Board, Brain Tumor Charity, 2016 - 2018

      Member, Scientific Evaluation Committee, INSERM; Cancer Research Centre of Toulouse, 2014

      Member, Scientific Advisory Board, Vesalius Research Center (VRC); Vlaams Institute of Biotechnology (VIB), 2013

      Member, Scientific Advisory Board, European Institute of Oncology, 2013

      Member, P01 Advisory Board, Sanford Burnham Prebys Medical Discovery Institutee, 2012

      Editorial Activities

      Guest Editor - Metabolism Collection, BMC Biology, 2026 - 2026

      Senior Editor, Cancer Research, 2018 - 2022

      Advisory Editorial Board, EMBO reports, 2017 - Present

      Advisory Editorial Board, Cell Chemical Biology, 2016 - Present

      Editorial Board, Molecular and Cellular Biology, 2013 - 2015

      Senior Editor, Cancer and Metabolism, 2012 - 2020

      Editor, Cell Death and Differentiation, 2011 - 2018

      Editor, Oncogene, 2009 - 2013

      Selected Publications

      Peer-Reviewed Articles

      1. Ghrayeb A, Finney AC, Agranovich B, Peled D, Anand SK, McKinney MP, Sarji M, Yang D, Weissman N, Drucker S, Fernandes SI, Fernandez-Garcia J, Mahan K, Abassi Z, Tan L, Lorenzi PL, Traylor J, Zhang J, Abramovich I, Chen YE, Rom O, Mor I, Gottlieb E. Serine synthesis via reversed SHMT2 activity drives glycine depletion and acetaminophen hepatotoxicity in MASLD. Cell Metab 36(1):116-129.e7, 2024. e-Pub 2024. PMID: 38171331.
      2. Zheng L, Zhu ZR, Sneh T, Zhang WT, Wang ZY, Wu GY, He W, Qi HG, Wang H, Wu XY, Fernandez-Garcia J, Abramovich I, Xu YZ, Zhang J, Gottlieb E. Circulating succinate-modifying metabolites accurately classify and reflect the status of fumarate hydratase-deficient renal cell carcinoma. J Clin Invest 133(11), 2023. e-Pub 2023. PMID: 37053010.
      3. Willi L, Abramovich I, Fernandez-Garcia J, Agranovich B, Shulman M, Milman H, Baskin P, Eisen B, Michele DE, Arad M, Binah O, Gottlieb E. Bioenergetic and Metabolic Impairments in Induced Pluripotent Stem Cell-Derived Cardiomyocytes Generated from Duchenne Muscular Dystrophy Patients. Int J Mol Sci 23(17), 2022. e-Pub 2022. PMID: 36077200.
      4. Savino AM, Fernandes SI, Olivares O, Zemlyansky A, Cousins A, Markert EK, Barel S, Geron I, Frishman L, Birger Y, Eckert C, Tumanov S, MacKay G, Kamphorst JJ, Herzyk P, Fernandez-Garcia J, Abramovich I, Mor I, Bardini M, Barin E, Janaki-Raman S, Cross JR, Kharas MG, Gottlieb E, Izraeli S, Halsey C. Metabolic adaptation of acute lymphoblastic leukemia to the central nervous system microenvironment is dependent on Stearoyl CoA desaturase. Nat Cancer 1(10):998-1009, 2020. e-Pub 2020. PMID: 33479702.
      5. van der Reest J, Lilla S, Zheng L, Zanivan S, Gottlieb E. Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress. Nat Commun 9(1):1581, 2018. e-Pub 2018. PMID: 29679077.
      6. 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 23(10):1234-1240, 2017. e-Pub 2017. PMID: 28920959.
      7. 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, Morkve SH, Lund-Johansen M, Chalmers AJ, Bjerkvig R, Niclou SP, Gottlieb E. Glutamine synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma. Nat Cell Biol 17(12):1556-68, 2015. e-Pub 2015. PMID: 26595383.
      8. Cardaci S, Zheng L, MacKay G, van den Broek NJ, MacKenzie ED, Nixon C, Stevenson D, Tumanov S, Bulusu V, Kamphorst JJ, Vazquez A, Fleming S, Schiavi F, Kalna G, Blyth K, Strathdee D, Gottlieb E. Pyruvate carboxylation enables growth of SDH-deficient cells by supporting aspartate biosynthesis. Nat Cell Biol 17(10):1317-26, 2015. e-Pub 2015. PMID: 26302408.
      9. Mackay GM, Zheng L, van den Broek NJ, Gottlieb E. Analysis of Cell Metabolism Using LC-MS and Isotope Tracers. Methods Enzymol 561:171-96, 2015. e-Pub 2015. PMID: 26358905.
      10. Zheng L, Cardaci S, Jerby L, MacKenzie ED, Sciacovelli M, Johnson TI, Gaude E, King A, Leach JD, Edrada-Ebel R, Hedley A, Morrice NA, Kalna G, Blyth K, Ruppin E, Frezza C, Gottlieb E. Fumarate induces redox-dependent senescence by modifying glutathione metabolism. Nat Commun 6:6001, 2015. e-Pub 2015. PMID: 25613188.
      11. 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 27(1):57-71, 2015. e-Pub 2015. PMID: 25584894.
      12. Duran 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 32(38):4549-56, 2013. e-Pub 2013. PMID: 23085753.
      13. Zheng L, MacKenzie ED, Karim SA, Hedley A, Blyth K, Kalna G, Watson DG, Szlosarek P, Frezza C, Gottlieb E. Reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells. Cancer Metab 1(1):12, 2013. e-Pub 2013. PMID: 24280230.
      14. Chaneton B, Hillmann P, Zheng L, Martin ACL, Maddocks ODK, Chokkathukalam A, Coyle JE, Jankevics A, Holding FP, Vousden KH, Frezza C, O'Reilly M, Gottlieb E. Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature 491(7424):458-462, 2012. e-Pub 2012. PMID: 23064226.
      15. Frezza C, Zheng L, Tennant DA, Papkovsky DB, Hedley BA, Kalna G, Watson DG, Gottlieb E. Metabolic profiling of hypoxic cells revealed a catabolic signature required for cell survival. PLoS One 6(9):e24411, 2011. e-Pub 2011. PMID: 21912692.
      16. 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. Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature 477(7363):225-8, 2011. e-Pub 2011. PMID: 21849978.
      17. Schug ZT, Gonzalvez F, Houtkooper RH, Vaz FM, Gottlieb E. BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane. Cell Death Differ 18(3):538-48, 2011. e-Pub 2011. PMID: 21072056.
      18. Tennant DA, Gottlieb E. HIF prolyl hydroxylase-3 mediates alpha-ketoglutarate-induced apoptosis and tumor suppression. J Mol Med (Berl) 88(8):839-49, 2010. e-Pub 2010. PMID: 20383689.
      19. Tennant DA, Frezza C, MacKenzie ED, Nguyen QD, Zheng L, Selak MA, Roberts DL, Dive C, Watson DG, Aboagye EO, Gottlieb E. Reactivating HIF prolyl hydroxylases under hypoxia results in metabolic catastrophe and cell death. Oncogene 28(45):4009-21, 2009. e-Pub 2009. PMID: 19718054.
      20. Gonzalvez F, Schug ZT, Houtkooper RH, MacKenzie ED, Brooks DG, Wanders RJ, Petit PX, Vaz FM, Gottlieb E. Cardiolipin provides an essential activating platform for caspase-8 on mitochondria. J Cell Biol 183(4):681-96, 2008. e-Pub 2008. PMID: 19001123.
      21. MacKenzie ED, Selak MA, Tennant DA, Payne LJ, Crosby S, Frederiksen CM, Watson DG, Gottlieb E. Cell-permeating alpha-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells. Mol Cell Biol 27(9):3282-9, 2007. e-Pub 2007. PMID: 17325041.
      22. Selak MA, Duran RV, Gottlieb E. Redox stress is not essential for the pseudo-hypoxic phenotype of succinate dehydrogenase deficient cells. Biochim Biophys Acta 1757(5-6):567-72, 2006. e-Pub 2006. PMID: 16797480.
      23. Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD, Pan Y, Simon MC, Thompson CB, Gottlieb E. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell 7(1):77-85, 2005. e-Pub 2005. PMID: 15652751.

      Invited Articles

      1. Boulahbel H, Duran RV, Gottlieb E. Prolyl hydroxylases as regulators of cell metabolism. Biochem Soc Trans 37(Pt 1):291-4, 2009. e-Pub 2009. PMID: 19143649.

      Review Articles

      1. Peled D, Casey R, Gottlieb E. Knowledge-Based Therapeutics for Tricarboxylic Acid (TCA) Cycle-Deficient Cancers. Cold Spring Harb Perspect Med 14(9), 2024. e-Pub 2024. PMID: 38503501.
      2. Schug ZT, Vande Voorde J, Gottlieb E. The metabolic fate of acetate in cancer. Nat Rev Cancer 16(11):708-717, 2016. e-Pub 2016. PMID: 27562461.
      3. Vazquez A, Kamphorst JJ, Markert EK, Schug ZT, Tardito S, Gottlieb E. Cancer metabolism at a glance. J Cell Sci 129(18):3367-73, 2016. e-Pub 2016. PMID: 27635066.
      4. Nowicki S, Gottlieb E. Oncometabolites: tailoring our genes. FEBS J 282(15):2796-805, 2015. e-Pub 2015. PMID: 25864878.
      5. Chaneton B, Gottlieb E. Rocking cell metabolism: revised functions of the key glycolytic regulator PKM2 in cancer. Trends Biochem Sci 37(8):309-16, 2012. e-Pub 2012. PMID: 22626471.
      6. Schug ZT, Frezza C, Galbraith LC, Gottlieb E. The music of lipids: how lipid composition orchestrates cellular behaviour. Acta Oncol 51(3):301-10, 2012. e-Pub 2012. PMID: 22283492.
      7. Frezza C, Pollard PJ, Gottlieb E. Inborn and acquired metabolic defects in cancer. J Mol Med (Berl) 89(3):213-20, 2011. e-Pub 2011. PMID: 21301796.
      8. Tennant DA, Duran RV, Gottlieb E. Targeting metabolic transformation for cancer therapy. Nat Rev Cancer 10(4):267-77, 2010. e-Pub 2010. PMID: 20300106.
      9. King A, Gottlieb E. Glucose metabolism and programmed cell death: an evolutionary and mechanistic perspective. Curr Opin Cell Biol 21(6):885-93, 2009. e-Pub 2009. PMID: 19850457.
      10. Schug ZT, Gottlieb E. Cardiolipin acts as a mitochondrial signalling platform to launch apoptosis. Biochim Biophys Acta 1788(10):2022-31, 2009. e-Pub 2009. PMID: 19450542.
      11. Tennant DA, Duran RV, Boulahbel H, Gottlieb E. Metabolic transformation in cancer. Carcinogenesis 30(8):1269-80, 2009. e-Pub 2009. PMID: 19321800.
      12. Frezza C, Gottlieb E. Mitochondria in cancer: not just innocent bystanders. Semin Cancer Biol 19(1):4-11, 2009. e-Pub 2009. PMID: 19101633.
      13. Gonzalvez F, Gottlieb E. Cardiolipin: setting the beat of apoptosis. Apoptosis 12(5):877-85, 2007. e-Pub 2007. PMID: 17294083.
      14. King A, Selak MA, Gottlieb E. Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene 25(34):4675-82, 2006. e-Pub 2006. PMID: 16892081.

      Editorials

      1. Krauss D, Gottlieb E. Restraining colorectal cancer with alphaKG. Nat Cancer 1(3):267-269, 2020. PMID: 35122033.
      2. Kamphorst JJ, Gottlieb E. Commentary: Friendly neighbours feed tumour cells. Nature 536:401-402, 2016. PMID: 27509862.
      3. van der Reest J, Gottlieb E. Commentary: Anti-cancer effects of vitamin C revisited. Cell Res 26:269-270, 2016. PMID: 26768769.
      4. Schug ZT, Vande Voorde J, Gottlieb E. Commentary: The Nurture of tumors can drive their metabolic phenotype. Cell Metab 23:391-392, 2016. PMID: 26959177.
      5. Chaneton B, Gottlieb E. PGAMgnam style: a glycolytic switch controls biosynthesis. Cancer Cell 22(5):565-6, 2012. PMID: 23153529.
      6. Frezza C, Tennant DA, Gottlieb E. IDH1 mutations in gliomas: when an enzyme loses its grip. Cancer Cell 17(1):7-9, 2010. PMID: 20129244.
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