Assoc Prof Charles Chuah

Dr Charles Chuah is currently a Senior Consultant at the Department of Haematology, Singapore General Hospital (SGH), Associate Professor at the Cancer and Stem Cell Biology Program, Duke-NUS Medical School and Clinical Senior Lecturer, Yong Loo Lin School of Medicine, National University of Singapore. He holds administrative appointments as Vice Chair Research, SingHealth Duke-NUS Academic Clinical Program for Medicine; Director, Research, SingHealth Duke-NUS Blood Cancer Centre; and Lead, Molecular Laboratory and Myeloproliferative Disorders/Chronic Myeloid Leukemia Service, Department of Haematology, SGH.

Dr Chuah has a strong and active interest in clinical and translational research in chronic myeloid leukaemia (CML) and targeted therapy for blood cancer. His research interests include mechanisms of resistance and targeted therapy in CML. In the past eleven years, he has been awarded four national grants and five institutional grants with a total funding of S$2.8 million. He was also awarded the National Medical Research Council Clinician Scientist Award in 2007 and 2010. Dr Chuah is a principal investigator in more than twenty multi-centre clinical trials.

Dr Chuah has authored or co-authored over 60 publications in peer-reviewed scientific journals including Nature, Nature Medicine, Nature Genetics, New England Journal of Medicine, Cancer Cell, PNAS, Blood, Leukemia and Journal of Clinical Oncology. He was a member of the Scientific Review Panel of the NMRC from 2007 to 2018. He was the Co-chair for the National Comprehensive Cancer Network (Asia) Consensus Statement Panel for CML in 2008.

• ​Doctor of Medicine, University of London, UK 2006
• Member of the Royal College of Physicians, MRCP UK 1999 
• Master of Medicine, MMED National University of Singapore 1999
• Bachelors of Medicine and Surgery, MBBS University of Aberdeen 1994

• Associate Professor at the Cancer and Stem Cell Biology Program, Duke-NUS Medical School
• Clinical Senior Lecturer, Yong Loo Lin School of Medicine, National University of Singapore
• Director, Office of Translational Medicine Oversight, SGH　
• Vice-Chair Research, SingHealth Duke-NUS Academic Clinical Program for Medicine
• Director, Research, SingHealth Duke-NUS Blood Cancer Centre
• Lead, Molecular Laboratory and Myeloproliferative Disorders/Chronic Myeloid Leukemia Service, Department of Haematology, SGH

• ​Chronic myeloid leukaemia
• Targeted therapy for blood cancer

• Cortes J, Apperley J, Lomaia E, Moiraghi B, Undurraga Sutton M, Pavlovsky C, et al. Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: a randomized, open-label phase 2 clinical trial. Blood. 2021 Nov;138(21):2042–50.
  
• Lee W-HS, Ye Z, Cheung AMS, Goh YPS, Oh HLJ, Rajarethinam R, et al. Effective Killing of Acute Myeloid Leukemia by TIM-3 Targeted Chimeric Antigen Receptor T Cells. Mol Cancer Ther. 2021 Sep;20(9):1702–12.
  
• Chuah C, Koh LP, Numbenjapon T, Zang DY, Ong KH, Do YR, et al. Efficacy and safety of bosutinib versus imatinib for newly diagnosed chronic myeloid  leukemia in the Asian subpopulation of the phase 3 BFORE trial. Int J Hematol. 2021 Jul;114(1):65–78.
  
• Asari K, Sun WT, Kok ZH, Lam YH, Ng BL, Saunders V, et al. Simvastatin enhances the efficacy of nilotinib in chronic myeloid leukaemia by post-translational modification and drug transporter modulation. Anticancer Drugs. 2021 Jun;32(5):526–36.
  
• Sinnakannu JR, Lee KL, Cheng S, Li J, Yu M, Tan SP, et al. SRSF1 mediates cytokine-induced impaired imatinib sensitivity in chronic myeloid  leukemia. Leukemia. 2020 Jul;34(7):1787–98.
  
• Bajaj J, Hamilton M, Shima Y, Chambers K, Spinler K, Van Nostrand EL, et al. An in vivo genome-wide CRISPR screen identifies the RNA-binding protein Staufen2 as a key regulator of myeloid leukemia. Nat cancer. 2020 Apr;1(4):410–22.
  
• Ko TK, Javed A, Lee KL, Pathiraja TN, Liu X, Malik S, et al. An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia. Blood. 2020 Jun;135(26):2337–53.
  
• Than H, Lye WK, Sng C, Allen JCJ, Ong ST, Chuah C. BIM deletion polymorphism profiling complements prognostic values of risk scores in imatinib-treated Asian chronic myeloid leukemia patients. Vol. 60, Leukemia & lymphoma. United States; 2019. p. 234–7.
  
• Lam Yi H, Than H, Sng C, Cheong MA, Chuah C, Xiang W. Lysosome Inhibition by Mefloquine Preferentially Enhances the Cytotoxic Effects of Tyrosine Kinase Inhibitors in Blast Phase Chronic Myeloid Leukemia. Transl Oncol. 2019 Sep;12(9):1221–8.
  
• Branford S, Kim DDH, Apperley JF, Eide CA, Mustjoki S, Ong ST, et al. Laying the foundation for genomically-based risk assessment in chronic myeloid  leukemia. Leukemia. 2019 Aug;33(8):1835–50.
  
• Durrant ST, Nagler A, Guglielmelli P, Lavie D, le Coutre P, Gisslinger H, et al. Results from HARMONY: an open-label, multicenter, 2-arm, phase 1b, dose-finding study assessing the safety and efficacy of the oral combination of ruxolitinib and buparlisib in patients with myelofibrosis. Vol. 104, Haematologica. 2019. p. e551–4.
  
• Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim D-W, et al. Patient-reported outcomes in the phase 3 BFORE trial of bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia. J Cancer Res Clin Oncol. 2019 Jun;145(6):1589–99.
  
• Ng KP, Manjeri A, Lee LM, Chan ZE, Tan CY, Tan QD, et al. The arginase inhibitor Nω-hydroxy-nor-arginine (nor-NOHA) induces apoptosis in leukemic cells specifically under hypoxic conditions but CRISPR/Cas9 excludes arginase 2 (ARG2) as the functional target. PLoS One. 2018;13(10):e0205254.
  
• Yang H, Chennamaneni LR, Ho MWT, Ang SH, Tan ESW, Jeyaraj DA, et al. Optimization of Selective Mitogen-Activated Protein Kinase Interacting Kinases 1 and 2 Inhibitors for the Treatment of Blast Crisis Leukemia. J Med Chem. 2018 May;61(10):4348–69.
  
• Cortes JE, Kim D-W, Pinilla-Ibarz J, le Coutre PD, Paquette R, Chuah C, et al. Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood. 2018 Jul;132(4):393–404.
  
• Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim D-W, et al. Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From  the Randomized BFORE Trial. J Clin Oncol Off J Am Soc Clin Oncol. 2018 Jan;36(3):231–7.
  
• Abaza YM, Kadia TM, Jabbour EJ, Konopleva MY, Borthakur G, Ferrajoli A, et al. Phase 1 dose escalation multicenter trial of pracinostat alone and in combination with azacitidine in patients with advanced hematologic malignancies. Cancer. 2017 Dec;123(24):4851–9.
  
• Nicolini FE, Basak GW, Kim D-W, Olavarria E, Pinilla-Ibarz J, Apperley JF, et al. Overall survival with ponatinib versus allogeneic stem cell transplantation in Philadelphia chromosome-positive leukemias with the T315I mutation. Cancer. 2017 Aug;123(15):2875–80.
  
• Rauzan M, Chuah CTH, Ko TK, Ong ST. The HDAC inhibitor SB939 overcomes resistance to BCR-ABL kinase Inhibitors conferred by the BIM deletion polymorphism in chronic myeloid leukemia. PLoS One. 2017;12(3):e0174107.
  
• Bajaj J, Konuma T, Lytle NK, Kwon HY, Ablack JN, Cantor JM, et al. CD98-Mediated Adhesive Signaling Enables the Establishment and Propagation of Acute Myelogenous Leukemia. Cancer Cell. 2016 Nov;30(5):792–805.
  
• Cortes JE, Saglio G, Kantarjian HM, Baccarani M, Mayer J, Boqué C, et al. Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial. J Clin Oncol Off J Am Soc Clin Oncol. 2016 Jul;34(20):2333–40.
  
• Lipton JH, Chuah C, Guerci-Bresler A, Rosti G, Simpson D, Assouline S, et al. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2016 May;17(5):612–21.
  
• Sun WT, Xiang W, Ng BL, Asari K, Bunte RM, Casey PJ, et al. Inhibition of isoprenylcysteine carboxylmethyltransferase augments BCR-ABL1 tyrosine kinase inhibition-induced apoptosis in chronic myeloid leukemia. Exp Hematol. 2016 Mar;44(3):189-93.e2.
  
• Ko TK, Chin HS, Chuah CTH, Huang JWJ, Ng K-P, Khaw SL, et al. The BIM deletion polymorphism: A paradigm of a permissive interaction between germline and acquired TKI resistance factors in chronic myeloid leukemia. Oncotarget. 2016 Jan;7(3):2721–33.
  
• Xiang W, Cheong JK, Ang SH, Teo B, Xu P, Asari K, et al. Pyrvinium selectively targets blast phase-chronic myeloid leukemia through inhibition of mitochondrial respiration. Oncotarget. 2015 Oct;6(32):33769–80.
  
• Ramlee MK, Yan T, Cheung AMS, Chuah CTH, Li S. High-throughput genotyping of CRISPR/Cas9-mediated mutants using fluorescent PCR-capillary gel electrophoresis. Sci Rep. 2015 Oct;5:15587.
  
• Kwon HY, Bajaj J, Ito T, Blevins A, Konuma T, Weeks J, et al. Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous  Leukemia. Cell Stem Cell. 2015 Aug;17(2):152–64.
  
• Cortes JE, Kantarjian HM, Rea D, Wetzler M, Lipton JH, Akard L, et al. Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic- or accelerated-phase chronic myeloid leukemia: Results with 24 months of follow-up. Cancer. 2015 May;121(10):1637–44.
  
• Tsai BP, Jimenez J, Lim S, Fitzgerald KD, Zhang M, Chuah CTH, et al. A novel Bcr-Abl-mTOR-eIF4A axis regulates IRES-mediated translation of LEF-1. Open Biol. 2014 Nov;4(11):140180.
  
• Ko TK, Chuah CTH, Huang JWJ, Ng K-P, Ong ST. The BCL2 inhibitor ABT-199 significantly enhances imatinib-induced cell death in chronic myeloid leukemia progenitors. Oncotarget. 2014 Oct;5(19):9033–8.
  
• Ong ST, Chuah CTH, Ko TK, Hillmer AM, Lim W-T. Reply: the BIM deletion polymorphism cannot account for intrinsic TKI resistance of Chinese individuals with chronic myeloid leukemia. Vol. 20, Nature medicine. United States; 2014. p. 1090–1.
  
• Zabriskie MS, Eide CA, Tantravahi SK, Vellore NA, Estrada J, Nicolini FE, et al. BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia. Cancer Cell. 2014 Sep;26(3):428–42.
  
• Ng KP, Manjeri A, Lee KL, Huang W, Tan SY, Chuah CTH, et al. Physiologic hypoxia promotes maintenance of CML stem cells despite effective BCR-ABL1 inhibition. Blood. 2014 May;123(21):3316–26.
  
• Zimdahl B, Ito T, Blevins A, Bajaj J, Konuma T, Weeks J, et al. Lis1 regulates asymmetric division in hematopoietic stem cells and in leukemia. Nat Genet. 2014 Mar;46(3):245–52.
  
• Jabbour E, Kantarjian HM, Saglio G, Steegmann JL, Shah NP, Boqué C, et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2014 Jan;123(4):494–500.
  
• Chuah CT, Nakamae H, Shen ZX, Bradley-Garelik MB, Kim D-W. Efficacy and safety of dasatinib versus imatinib in the East Asian subpopulation of the DASISION trial of newly diagnosed chronic myeloid leukemia in chronic phase. Leuk Lymphoma. 2014 Sep;55(9):2093–100.
  
• Lim S, Saw TY, Zhang M, Janes MR, Nacro K, Hill J, et al. Targeting of the MNK-eIF4E axis in blast crisis chronic myeloid leukemia inhibits  leukemia stem cell function. Proc Natl Acad Sci U S A. 2013 Jun;110(25):E2298-307.
  
• Nicolini FE, Ibrahim AR, Soverini S, Martinelli G, Müller MC, Hochhaus A, et al. The BCR-ABLT315I mutation compromises survival in chronic phase chronic myelogenous  leukemia patients resistant to tyrosine kinase inhibitors, in a matched pair analysis. Haematologica. 2013 Oct;98(10):1510–6.
  
• Ng KP, Hillmer AM, Chuah CTH, Juan WC, Ko TK, Teo ASM, et al. A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat Med. 2012 Mar;18(4):521–8.
  
• Linn Y-C, Yong H-X, Niam M, Lim T-J, Chu S, Choong A, et al. A phase I/II clinical trial of autologous cytokine-induced killer cells as adjuvant immunotherapy for acute and chronic myeloid leukemia in clinical remission. Cytotherapy. 2012 Aug;14(7):851–9.
  
• Cortes J, Lipton JH, Rea D, Digumarti R, Chuah C, Nanda N, et al. Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation. Blood. 2012 Sep;120(13):2573–80.
  
• Chuah C. Imatinib does not impair gonadal function. Vol. 36, Leukemia research. England; 2012. p. 262–3.
  Nicolini FE, Basak GW, Soverini S, Martinelli G, Mauro MJ, Müller MC, et al. Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated  leukemias. Blood. 2011 Nov;118(20):5697–700.
  
• Lim AST, Chen TJ, Lim TH, Tan M, Lau LC, Lim P, et al. Bone marrow cytogenetics workup: Application of lean management system to determine if additional cell workup is helpful and necessary to analysis. Ann Acad Med Singapore. 2010 Sep;39(9):696–9.
  
• Ito T, Kwon HY, Zimdahl B, Congdon KL, Blum J, Lento WE, et al. Regulation of myeloid leukaemia by the cell-fate determinant Musashi. Nature. 2010 Aug;466(7307):765–8.
  
• Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010 Jun;362(24):2260–70.
  
• Tan CS, Chan KP, Chuah CT, Ng HJ, Cheah FK, Teo FS, et al. Life threatening and occult mediastinal haemorrhage secondary to acquired factor VIII deficiency. Vol. 38, Annals of the Academy of Medicine, Singapore. Singapore; 2009. p. 280–1.
  
• Nicolini FE, Mauro MJ, Martinelli G, Kim D-W, Soverini S, Müller MC, et al. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute  lymphoblastic leukemia patients with BCR-ABL T315I mutation. Blood. 2009 Dec;114(26):5271–8.
  
• Chuah C, Melo J V. Targeted treatment of imatinib-resistant chronic myeloid leukemia: Focus on  dasatinib. Onco Targets Ther. 2009 Feb;2:83–94.
  
• Au WY, Caguioa PB, Chuah C, Hsu SC, Jootar S, Kim D-W, et al. Chronic myeloid leukemia in Asia. Int J Hematol. 2009 Jan;89(1):14–23.
  
• Melo J V, Chuah C. Novel agents in CML therapy: tyrosine kinase inhibitors and beyond. Hematol Am Soc Hematol Educ Progr. 2008;427–35.
  
• Pavlu J, Andreasson C, Chuah C, Kaeda J, Goldman JM, Apperley JF, et al. Dual inhibition of ras and bcr-abl signalling pathways in chronic myeloid leukaemia:  a phase I/II study in patients in complete haematological remission. Br J Haematol. 2007 Jun;137(5):423–8.
  
• Melo J V, Chuah C. Resistance to imatinib mesylate in chronic myeloid leukaemia. Cancer Lett. 2007 May;249(2):121–32.
  
• Chuah C, Lim TH, Lim AST, Tien SL, Lim CH, Soong R, et al. Dasatinib induces a response in malignant thymoma. Vol. 24, Journal of clinical oncology: official journal of the American Society of Clinical Oncology. United States; 2006. p. e56-8.
  
• Gullo CA, Chuah CTH, Hwang WYK, Teoh GKH. Detection and quantification of the abelson tyrosine kinase domains of the BCR-ABL gene translocation in chronic myeloid leukaemia using genomic quantitative real-time polymerase chain reaction. Ann Acad Med Singapore. 2006 Oct;35(10):680–7.