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.
Present Title & Affiliation
Primary Appointment
Vice President, Research, Division of Discovery Science, The University of Texas MD Anderson Cancer Center, Houston, Texas
Professor and R.E. Bob Smith Distinguished Chair in Cancer Biology, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Education & Training
Degree-Granting Education
| 2020 | Technion – Israel Institute of Technology, IL, MBA, Faculty of Industrial Engineering and Management |
| 1998 | Weizmann Institute of Science, IL, PhD, Molecular Cell Biology |
| 1993 | Weizmann Institute of Science, IL, MSc, Molecular Cell Biology |
| 1990 | The Hebrew University of Jerusalem, IL, BSc, Agriculture (Animal Sciences) |
Postgraduate Training
| 1999-2003 | Postgraduate Fellow, University of Pennsylvania, Pennsylvania, PA |
| 1998-1999 | Postgraduate Fellow, University of Chicago, Chicago, IL |
Experience & Service
Academic Appointments
Professor, Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, 2016 - 2022
Professor of Molecular Cell Biology, University of Glasgow, Glasgow, 2009 - 2018
Senior Research Group leader, Cancer Research UK, Beatson Institute, Glasgow, 2009 - 2018
Research Group Leader, Cancer Research UK, Beatson Institute, Glasgow, 2003 - 2009
Selected Publications
Peer-Reviewed Articles
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- 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.
Other Articles
- Peled D, Casey R, Gottlieb E Knowledge-Based Therapeutics for Tricarboxylic Acid (TCA) Cycle-Deficient Cancers. Cold Spring Harb Perspect Med 14(9), 2024. PMID: 38503501.
- Schug ZT, Vande Voorde J, Gottlieb E The metabolic fate of acetate in cancer. Nat Rev Cancer 16(11):708-717, 2016. PMID: 27562461.
- 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. PMID: 27635066.
- 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. PMID: 26358905.
- Nowicki S, Gottlieb E Oncometabolites: tailoring our genes. FEBS J 282(15):2796-805, 2015. PMID: 25864878.
- 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. PMID: 22626471.
- 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. PMID: 22283492.
- Frezza C, Pollard PJ, Gottlieb E Inborn and acquired metabolic defects in cancer. J Mol Med (Berl) 89(3):213-20, 2011. PMID: 21301796.
- Tennant DA, Duran RV, Gottlieb E Targeting metabolic transformation for cancer therapy. Nat Rev Cancer 10(4):267-77, 2010. PMID: 20300106.
- King A, Gottlieb E Glucose metabolism and programmed cell death: an evolutionary and mechanistic perspective. Curr Opin Cell Biol 21(6):885-93, 2009. PMID: 19850457.
- Schug ZT, Gottlieb E Cardiolipin acts as a mitochondrial signalling platform to launch apoptosis. Biochim Biophys Acta 1788(10):2022-31, 2009. PMID: 19450542.
- Tennant DA, Duran RV, Boulahbel H, Gottlieb E Metabolic transformation in cancer. Carcinogenesis 30(8):1269-80, 2009. PMID: 19321800.
- Frezza C, Gottlieb E Mitochondria in cancer: not just innocent bystanders. Semin Cancer Biol 19(1):4-11, 2009. PMID: 19101633.
- Gonzalvez F, Gottlieb E Cardiolipin: setting the beat of apoptosis. Apoptosis 12(5):877-85, 2007. PMID: 17294083.
- King A, Selak MA, Gottlieb E Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene 25(34):4675-82, 2006. PMID: 16892081.
Editorials
- Krauss D, Gottlieb E. Restraining colorectal cancer with alphaKG. Nat Cancer 1(3):267-269, 2020. PMID: 35122033.
- Kamphorst JJ, Gottlieb E. Commentary: Friendly neighbours feed tumour cells. Nature 536:401-402, 2016. PMID: 27509862.
- van der Reest J, Gottlieb E. Commentary: Anti-cancer effects of vitamin C revisited. Cell Res 26:269-270, 2016. PMID: 26768769.
- 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.
- Chaneton B, Gottlieb E. PGAMgnam style: a glycolytic switch controls biosynthesis. Cancer Cell 22(5):565-6, 2012. PMID: 23153529.
- 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.
Patient Reviews
CV information above last modified March 06, 2025