CURRICULUM VITAE

Thilo Hagen

Address: Department of Biochemistry, National University of Singapore, 8 Medical Drive, MD7 level 3, 117597 Singapore

Email: bchth@nus.edu.sg

Current Position: Associate Professor, Department of Biochemistry

Education

1996 – Primary medical qualification and M.D. degree, Humboldt-University Berlin, Germany (M.D. thesis on “Net adenine nucleotide transport in rat kidney mitochondria”)

1998 – Full medical qualification

Past employment history:

1996-1998 – Postdoctoral Research Fellow, Department of Biology, Tufts University and Departments of Genetics and Laboratory Medicine, Children’s Hospital, Harvard Medical School Boston, MA (Regulation of mitochondrial biogenesis and Development of enzymatic and gas chromatography/mass spectrometry-based methods for the diagnosis of inherited metabolic disorders)

1998-2000 – Postdoctoral Research Fellow, Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, MA (Characterisation of the function and regulation of mitochondrial uncoupling proteins)

2000-2001 – Postdoctoral Research Fellow, Neurology Centre of Excellence in Drug Discovery, GlaxoSmithKline, Harlow, Essex, UK (Role of glycogen synthase kinase-3 (GSK-3) in Wnt signalling)

2001-2003 – Postdoctoral Research Fellow, Wolfson Institute for Biomedical Research, University College London (Role of nitric oxide as a signalling molecule)

2003-2007 – Lecturer, Wolfson Digestive Diseases Centre, University of Nottingham

2007-2013 – Assistant Professor, Department of Biochemistry, National University of Singapore

Awards

2015 – NUS Faculty of Science Annual Teaching Award AY2014/15

2016 – NUS Yong Loo Lin School of Medicine Teaching Excellence Award AY2015/16

2017 – NUS Faculty of Science Annual Teaching Award AY2016/17

2018 – NUS Faculty of Science Annual Teaching Award AY2017/18

Professional Memberships

Singapore Society for Biochemistry and Molecular Biology (SSBMB), Vice President

Research Interests

Cellular signalling, Cellular metabolism, Ageing and mitochondria

PUBLICATIONS

  1. T Hagen, JL Joyal, W Henke, JR Aprille. Net adenine nucleotide transport in rat kidney mitochondria. Arch. Biochem. Biophys. 303:195-207 (1993)
  2. JL Joyal, T Hagen, JR Aprille. Intramitochondrial protein synthesis is regulated by matrix adenine nucleotide content and requires calcium. Arch. Biochem. Biophys. 319:322-30 (1995)
  3. T Hagen, M Ziegler. Detection and identification of NAD-catabolizing activities in rat tissue homogenates. Biochim. Biophys. Acta 1340:7-12 (1997)
  4. W Henke, T Hagen, K Jung, SA Loening. Periodate-oxidized ATP stimulates the permeability transition of rat liver mitochondria. Biochim. Biophys. Acta 1363:209-16 (1998)
  5. N Rifai, T Hagen, L Bradley, M Sakamoto. Determination of serum physiological concentration of methylmalonic acid by gas chromatography-mass spectrometry with selected ion monitoring. Ann. Clin. Biochem. 35:633-6 (1998)
  6. T Hagen, MS Korson. Quantification of glutaric acid by isotope dilution mass spectrometry for patients with glutaric acidemia type I: selected ion monitoring vs. selected ion storage. Clin. Chim. Acta 282:185-95 (1999)
  7. T Hagen, MS Korson, M Sakamoto, JE Evans. A GC/MS/MS screening method for multiple organic acidemias from urine specimens. Clin. Chim. Acta 283:77-88 (1999)
  8. CY Zhang*, T Hagen*, VK Mootha, LJ Slieker, BB Lowell. Assessment of uncoupling activity of uncoupling protein 3 using a yeast heterologous expression system. FEBS Lett. 449:129-34 (1999)
  9. T Hagen*, CY Zhang*, LJ Slieker, BB Lowell. Assessment of the uncoupling activity of human uncoupling protein short form and three mutants of the UCP3 gene using a yeast heterologous expression system. FEBS Lett. 454:201-6 (1999)
  10. T Hagen, MS Korson, JI Wolfsdorf. Urinary lactate excretion to monitor the efficacy of treatment of type I glycogen storage disease. Mol. Genet. Metab. 70:189-95 (2000)
  11. AJ Vidal-Puig, D Grujic, CY Zhang, T Hagen, O Boss, Y Ido, A Szczepanik, J Wade, V Mootha, R Cortright, DM Muoio, BB Lowell. Energy Metabolism in Uncoupling protein 3 knockout mice. J. Biol. Chem. 275:16258-66 (2000)
  12. T Hagen, CY Zhang, CR Vianna, BB Lowell. Uncoupling proteins 1 and 3 are regulated differently. Biochemistry 39:3845-51 (2000)
  13. T Hagen, BB Lowell. Chimeric proteins between UCP1 and UCP3: the middle third of UCP1 is necessary and sufficient for activation by fatty acids. Biochem. Biophys. Res. Commun. 276:642-48 (2000)
  14. O Boss, T Hagen, BB Lowell. Uncoupling proteins 2 and 3: Potential regulators of mitochondrial energy metabolism. Diabetes 49:143-56 (Review) (2000)
  15. CR Vianna, T Hagen, CY Zhang, E Bachman, O Boss, B Gereben, AS Moriscot, BB Lowell, J Eduardo, PW Bicudo, AC Bianco. Cloning and functional characterization of an uncoupling protein homolog in hummingbirds. Physiol. Genomics 5:137-45 (2001)
  16. CY Zhang, G Baffy, P Perret, S Krauss, O Peroni, D Grujic, T Hagen, AJ Vidal-Puig, O Boss, XX Zheng, MB Wheeler, GI Shulman, C Chan, BB Lowell. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, β-cell dysfunction and type 2 diabetes. Cell 105:745-55 (2001)
  17. AA Culbert, MJ Brown, S Frame, T Hagen, DA Cross, B Bax, AD Reith. GSK-3 inhibition by Adenoviral FRAT1 overexpression is neuroprotective and induces Tau dephosphorylation and β-catenin stabilisation without elevation of glycogen synthase activity. FEBS Lett. 507:288-94 (2001)
  18. T Hagen, A Vidal-Puig. Mitochondrial uncoupling proteins in human physiology and disease. Minerva Med. 93:41-57 (Review) (2002)
  19. T Hagen, A Vidal-Puig. Characterisation of the phosphorylation of β-catenin at the GSK-3 priming site Ser45. Biochem. Biophys. Res. Commun. 294:324-28 (2002)
  20. T Hagen, E Di Daniel, AA Culbert, AD Reith. Expression and characterization of GSK-3 mutants and their effect on β-catenin phosphorylation in intact cells. J. Biol. Chem. 277:23330-5 (2002)
  21. T Hagen, CJ Lagace, JS Modica-Napolitano, JR Aprille. Permeability Transition in rat liver mitochondria is modulated by the ATP-Mg/Phosphate carrier. Am. J. Physiol. 285:G274-G81 (2003)
  22. T Hagen, CT Taylor, F Lam, S Moncada. Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1α. Science 302:1975-1978 (2003)
  23. T Hagen, JK Sethi, N Foxwell, A Vidal-Puig. Signalling activity of β-catenin targeted to different subcellular compartments. Biochem. J. 379:471-77 (2004)
  24. T Hagen, G D’Amico G, M Quintero, M Palacios-Callender, V Hollis, F Lam, S Moncada. Inhibition of mitochondrial respiration by the anticancer agent 2-methoxyestradiol. Biochem. Biophys. Res. Commun. 322:923-9 (2004)
  25. EH Chew, CS Matthews, J Zhang, AJ McCarroll, T Hagen, MF Stevens, AD Westwell, TD Bradshaw. Antitumor quinols: role of glutathione in modulating quinol-induced apoptosis and identification of putative cellular protein targets. Biochem. Biophys. Res. Commun. 346: 242-51 (2006)
  26. G D’Amico, F Lam, T Hagen, S Moncada. Inhibition of cellular respiration by endogenously produced Carbon Monoxide. J. Cell Sci. 119:2291-8 (2006)
  27. T Hagen, DA Cross, AA Culbert, A West, S Frame, N Morrice, AD Reith. FRAT1, a substrate-specific regulator of GSK-3 activity, is a cellular substrate of Protein Kinase A. J. Biol. Chem. 281:35021-9 (2006)
  28. EH Chew, T Poobalasingam, CJ Hawkey, T Hagen. Characterization of cullin-based E3 ubiquitin ligases in intact mammalian cells – Evidence for Cullin dimerization. Cell. Signal. 19:1071-80 (2007)
  29. EH Chew, T Hagen. Substrate-mediated regulation of cullin neddylation. J. Biol. Chem. 282:17032-40 (2007)
  30. D Najat, T Garner, T Hagen, B Shaw, PW Sheppard, A Falchetti, F Marini, ML Brandi, JE Long, JR Cavey, MS Searle, R Layfield. Characterization of a non-UBA domain missense mutation of sequestosome 1 (SQSTM1) in Paget’s disease of bone. J. Bone Miner. Res. 24:632-42 (2009)
  31. T Hagen. Characterization of the interaction between latency-associated nuclear antigen and glycogen synthase kinase 3beta. J. Virol. 83:6312-7 (2009)
  32. FF Gan, YS Chua, S Scarmagnani, P Palaniappan, M Franks, T Poobalasingam, TD Bradshaw, AD Westwell, T Hagen. Structure-activity analysis of 2’-modified Cinnamaldehyde analogues as potential anticancer agents. Biochem. Biophys. Res. Commun. 387:741-7 (2009)
  33. YS Chua, YL Chua, T Hagen. Structure activity analysis of 2-Methoxyestradiol analogues reveals targeting of microtubules as the major mechanism of antiproliferative and proapoptotic activity. Mol. Cancer Ther. 9: 224-35. (2010)
  34. JJ Lou, YL Chua, EH Chew, J Gao, M Bushell, T Hagen. Inhibition of Hypoxia-Inducible Factor-1a (HIF-1α) protein synthesis by DNA damage inducing agents. PLOS One 5:e10522 (2010)
  35. DP Wong, G Wells, T Hagen. Heteroaromatic 4-arylquinols are novel inducers of Nuclear factor-erythroid 2-related factor 2 (Nrf2). Eur J. Pharmacol. 643:188-94 (2010)
  36. YC Leck, YY Choo, CY Tan, PG Smith, T Hagen. Biochemical and cellular effects of inhibiting Nedd8 conjugation. Biochem. Biophys. Res. Commun. 398:588-93 (2010)
  37. FX Yu, TF Chai, H He, T Hagen, Y Luo. Thioredoxin-interacting protein (TXNIP) gene expression: Sensing oxidative phosphorylation status and glycolytic rate. J. Biol. Chem. 285:25822-30 (2010)
  38. YL Chua, E Dufour, EP Dassa, P Rustin, HT Jacobs, CT Taylor, T Hagen. Stabilization of HIF-1alpha protein in hypoxia occurs independently of mitochondrial reactive oxygen species production J. Biol. Chem. 285:31277-84 (2010)
  39. TF Chai, YC Leck, H He, FX Yu, Y Luo, T Hagen. Hypoxia-inducible factor independent down-regulation of thioredoxin-interacting protein in hypoxia. FEBS Lett. 585:492-8 (2011)
  40. YS Chua, BK Boh, W Ponyeam, T Hagen. Regulation of Cullin RING E3 ubiquitin ligases by CAND1 in vivo. PLOS One 6:e16071 (2011)
  41. YL Chua, T Hagen. Compound C prevents Hypoxia-Inducible Factor-1α protein stabilization by regulating the cellular oxygen availability via interaction with Mitochondrial Complex I. BMC Res. Notes 4:117 (2011)
  42. BK Boh, PG Smith, T Hagen. Neddylation-induced conformational control regulates Cullin RING Ligases activity in vivo. J. Mol. Biol. 409:136–45 (2011)
  43. YY Choo, BK Boh, JJ Lou, J Eng, YC Leck, B Anders, PG Smith, T Hagen. Characterization of the role of COP9 signalosome in regulating Cullin E3 ubiquitin ligase activity. Mol. Biol. Cell 22:4706-15 (2011)
  44. BK Boh, MY Ng, YC Leck, B Shaw, J Long, GW Sun, YH Gan, MS Searle, R Layfield, T Hagen. Inhibition of Cullin RING Ligases by Cycle Inhibiting Factor: Evidence for Interference with Nedd8-Induced Conformational Control. J. Mol. Biol. 413:430-7 (2011)
  45. W Ponyeam, T Hagen. Characterization of the Cullin7 E3 ubiquitin ligase – heterodimerization of cullin substrate receptors as a novel mechanism to regulate cullin E3 ligase activity. Cell. Signal. 24:290-5 (2012)
  46. TF Chai, SY Hong, H He, T Hagen, Y Luo, FX Yu. A potential mechanism of metformin-mediated regulation of glucose homeostasis: inhibition of Thioredoxin-interacting protein (Txnip) gene expression. Cell. Signal. 24:1700-5 (2012)
  47. YY Choo, T Hagen. Mechanism of Cullin3 E3 Ubiquitin Ligase Dimerization. PLOS One 7:e41350 (2012)
  48. KY Goh, NW Ng, T Hagen, T Inoue. p21-Activated kinase interacts with Wnt signaling to regulate tissue polarity and gene expression. Proc Natl Acad Sci USA 109:15853-8 (2012)
  49. T Hagen. Oxygen versus Reactive Oxygen in the regulation of HIF-1a – The Balance Tips. Biochem Res Int (Review) (2012) Biochem. Res. Int. 2012:436981 (2012)
  50. CZ Hu, JK Sethi, T Hagen. The role of the cullin-5 E3 ubiquitin ligase in the regulation of insulin receptor substrate-1. Biochem. Res. Int. 2012:282648 (2012)
  51. CY Tan, T Hagen. Post-translational regulation of mTOR complex 1 in hypoxia and reoxygenation. Cell. Signal. 25:1235-44 (2013)
  52. RW Wong, T Hagen. Mechanistic target of rapamycin (mTOR) dependent regulation of thioredoxin interacting protein (TXNIP) transcription in hypoxia. Biochem. Biophys. Res. Commun. 433:40-6 (2013)
  53. SY Hong, T Hagen. Multiple myeloma Leu167Ile (c.499C>A) mutation prevents XBP1 mRNA splicing. Br. J. Haematol. 161:898-901 (2013)
  54. CY Tan, T Hagen. Destabilization of CDC6 upon DNA damage is dependent on neddylation but independent of Cullin E3 ligases. Int. J. Biochem. Cell Biol. 45:1489-98 (2013)
  55. CY Tan, T Hagen. mTORC1 dependent regulation of REDD1 protein stability. PLoS One 8:e63970 (2013)
  56. L Cordero-Espinoza, T Hagen. Regulation of Cullin-RING ubiquitin ligase 1 by Spliceosome-associated protein 130 (SAP130). Biol. Open 2:838-44 (2013)
  57. L Cordero-Espinoza, T Hagen. Increased concentrations of Fructose-2,6-bisphosphate contribute to the Warburg effect in PTEN-deficient cells. J. Biol. Chem. 288:36020-36008 (2013)
  58. A Gopalsamy, T Hagen, Swaminathan K. Investigating the molecular basis of Siah1 and Siah2 E3 ubiquitin ligase substrate specificity. PLoS One 9:e106547 (2014)
  59. SB Shelar, KK Kaminska, SA Reddy, D Kumar, CT Tan, VC Yu, J Lu, A Holmgren, T Hagen, EH Chew. Thioredoxin-dependent regulation of AIF-mediated DNA damage. Free Radic. Biol. Med. 87:125-36 (2015)
  60. SY Hong, T Hagen. 2-Deoxyglucose induces the expression of thioredoxin interacting protein (TXNIP) by increasing O-GlcNAcylation – Implications for targeting the Warburg effect in cancer cells. Biochem. Biophys. Res. Commun. 465:838-44 (2015)
  61. Y Shen, LF Ng, NP Low, T Hagen, J Gruber, T Inoue. C. elegans miro-1 Mutation Reduces the Amount of Mitochondria and Extends Life Span. PLoS One 11:e0153233 (2016)
  62. SY Hong, FX Yu, Y Luo, T Hagen. Oncogenic activation of the PI3K/Akt pathway promotes cellular glucose uptake by downregulating the expression of thioredoxin-interacting protein. Cell. Signal. 28:377-83 (2016)
  63. SY Hong, LT Ng, LF Ng, T Inoue, NS Tolwinski, T Hagen, J Gruber. The Role of Mitochondrial Non-Enzymatic Protein Acylation in Ageing. PLoS One 11:e0168752 (2016)
  64. MY Ng, M Wang, PJ Casey, YH Gan, T Hagen. Activation of MAPK/ERK signaling by Burkholderia pseudomallei cycle inhibiting factor (Cif). PLoS One 12:e0171464 (2017)
  65. A Karkhanis, JWH Leow, T Hagen, ECY Chan. Dronedarone-induced cardiac mitochondrial dysfunction and its mitigation by epoxyeicosatrienoic acids. Toxicol. Sci. 163:79-91(2018)
  66. MY Ng, YH Gan, T Hagen. Characterisation of cellular effects of Burkholderia pseudomallei cycle inhibiting factor (Cif). Biol. Open 7: bio028225 (2018)
  67. DPW Wong, MY Ng, JY Leung, BK Boh, EC Lim, SH Tan, S Lim, WH Seah, CZ Hu, BC Ho, DHP Ng, T Hagen. Regulation of the NRF2 transcription factor by andrographolide and organic extracts from plant endophytes. PLoS One 13:e0204853. (2018)