CHNG Wee Joo

Professor Chng Wee Joo’s research focus is on the use of global genomics methods (microarray and sequencing platforms) to study the clinical and biological heterogeneity in haematologic malignancies including acute myeloid leukemia, multiple myeloma and lymphoma. Using these methods, he has identified novel prognostic markers and well as molecular abnormalities in these malignancies that provide insights into disease pathogenesis and biology and serve as potential targets for therapy. This serve as an experimental therapeutic platform to also study new drugs in these disease and their mechanism of action and resistance.

The Haematological Malignancy Genomics Laboratory operates a comprehensive translational research program in haematological malignancies with focus on multiple myeloma (MM), acute myeloid leukemias (AML) and natural killer / T-cell Lymphoma (NKTL). At the core of this program is the use of high-throughput cutting edge genomics and proteomics techniques in human tumor samples and model system to make clinically relevant discoveries. These discoveries will encompass novel biological insights, identification of new diagnostic subtypes, prognostic factors, therapeutic targets, and aspects of molecular epidemiology and pharmacogenomics, all with potential impact on patient care. In this bench-to-bedside translational pipeline, discoveries are validated in the pre-clinical setting before clinical validation. The program will be supported by a comprehensive tissue bank that provides high-quality source materials for down-stream study, and a clinical database that is connected by a relational database for integrated system biology analysis (See Figure Below). In MM, we are focused on identifying the pathways leading to disease progression. In this regards, we have constructed step-wise pathways of progression for MM and is using this as a framework to design therapeutic intervention strategy. At the same time, we are using genomics to dissect the molecular heterogeneity of the disease. This has yielded robust genetic subtypes. We are now focusing on rationally targeting high-risk subtypes based on the underlying genomic aberrations and molecular defect. In AML, we have been working on mechanisms mediating therapeutic resistance in FLT3 positive AML, and in the process have identified novel molecules that play a fundamental role in leukemogenesis and may represent novel therapeutic targets. In addition, we are also testing novel compounds targeting EZH2, an oncogenic histone modifier, and has unraveled interesting biology in AML so far. In NKTL, we are using genomics to understand key molecular event mediating pathophysiology. Till now, we have identified key pathways that are activated and showed that most of these pathway activation is due to downregulation of regulating miRNAs. The downregulation of these miRNA are mediated by EBV infection or MYC activation. We also identified certain markers that are universally over-expressed in NKTL and may serve as novel therapeutic targets.

Selected Publications:

  1. V Selvarajan, J Yan, MF Ham, M Salto-Tellez, Dominic, Y Ito, WJ Chng*, SB Ng*. Characterization of the biological and clinical relevance of RUNX3 in Natural Killer/T-Cell lymphoma. Leukemia 2017; 31: 2219-2227.
  2. *WJ Chng, H Goldschmidt, MA Dimopoulos, P Moreau, D Joshua, A Palumbo, T Facon, H Ludwig, L Pour, R Niesvizky, A Oriol, L Rosiñol, A Suvorov, G Gaidano, T Pika, K Weisel, V Goranova-Marinova, HH Gillenwater, N Mohamed, S Feng, S Aggarwal, and R Hájek. Carfilzomib and Dexamethasone vs Bortezomib and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma Based on Cytogenetic Risk Status: Subgroup Analysis From the Phase 3 Study ENDEAVOR. Leukemia 2017; 31: 1368-74.
  3. Yan J, Li B, Lin B, Lee PT, Chung TH, Tan J, Bi C, Lee XT, Selvarajan V, Ng SB, Yang H, Yu Q, *Chng WJ. EZH2 phosphorylation by JAK3 mediates a switch to non-canonical function in natural killer/T-cell lymphoma. Blood 2016; 128: 948-58.
  4. *Chng WJ, Chung TH, Kumar S, Usmani S, Munshi N, Avet-Loiseau H, Goldschmidt H, Durie B, Sonneveld P. Gene signature combinations improve prognostic stratification of multiple myeloma patients. Leukemia 2016; 30: 1071-8.
  5. Mahara S, Lee PL, Feng M, Tergaonkar V, *Chng WJ, Yu Q. HIFI-α activation underlies a functional switch in the paradoxical role of Ezh2/PRC2 in breast cancer. Proc Natl Acad Sci U S A 2016: 113: E3735-44.
  6. Z Xie, C Bi, JY Chooi, ZL Chan, N Mustafa, and *WJ Chng. MMSET regulates transcription factors critical for survival of t(4;14) myeloma myeloma cells and its silence potentiates the effect of antimyeloma agents. Leukemia 2015; 29: 2347-54.
  7. PJ Teoh, TH Chung, C Sintosebastian, J Yan, SB Ng, R Fonseca, *WJ Chng. p53 haploinsufficiency and functional abnormalities in multiple myeloma. Leukemia 2014. 28: 2066-74.
  8. PSY Chong, J Zhou, LL Cheong, SC Liu, J Qian, T Guo, SK Sze, Q Zeng, *WJ Chng. LEO1 is Regulated by PRL-3 and Mediates Its Oncogenic Properties in Acute Myeloid Leukemia. Cancer Res 2014; 74: 3043-3053.
  9. *WJ Chng, A Dispenzieri, CS Chim, R Fonseca, H Goldschmidt, S Lentzsch, N Munshi, A Palumbo, J San Miguel, P Sonneveld, S Umani, BDG Durie, H Avet-Loiseau on Behalf of the International Myeloma Working Group. IMWG Consensus on Risk Stratification in Multiple Myeloma. Leukemia 2014; 28: 269-77.
  10. J Yan, SB Ng, JL Tay, B Lin, TL Koh, J Tan, V Selvarajan, SC Liu, C Bi, S Wang, SN Choo, N Shimizu, G Huang, Q Yu and *WJ Chng. EZH2 overexpression in natural killer/T-cell lymphoma confers growth advantage independently of histone methyltransferase activity. Blood 2013; 121: 4512-4520.
Name CHNG Wee Joo
Affiliations Deputy Director & Senior Principal Investigator, Cancer Science Institute of Singapore, NUS
Professor, Yong Loo Lin School of Medicine, National University of Singapore
Director, National University Cancer Institute, Singapore (NCIS)
Head and Senior Consultant, Division of Haematology, Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS)
Leader, Haematologic Malignancy Tumour Group, National University Cancer Institute, Singapore (NCIS)
Email mdccwj[at]nus.edu.sg

Education

Institute Degree (if applicable) Year(s)
University of Leeds MB ChB 1997
Membership of the Royal College of Physicians, UK MRCP 2000
Diploma Royal College of Pathologist, UK DipRCPath 2004
Membership of the Royal College of Pathologist, UK MRCPath 2005
National University of Singapore PhD 2011

Professional Experience

Professor, Yong Loo Lin School of Medicine, National University of Singapore 2015 – Present
Deputy Director, Cancer Science Institute of Singapore, National University of Singapore 2012 – Present
Senior Principal Investigator, Cancer Science Institute of Singapore, National University of Singapore 2008 – Present
Head, Division of Haematology, Department of Haematology-Oncology, NUH 2013 – Present
Senior Consultant, Division of Haematology, Department of Haematology-Oncology, National University Cancer Institute of Singapore, National University Health System 2012 – Present
Adjunct Assistant Professor in Medicine, Mayo Clinic College of Medicine, USA 2008 – Present
Consultant, Department of Haematology, National University Hospital, Singapore 2007 – 2012
Associate Professor, Yong Loo Lin School of Medicine, National University of Singapore 2008 – 2015
Research Collaborator in multiple myeloma genomics, Mayo Clinic Comprehensive Cancer Center, Scottsdale, Arizona, USA 2007 – Present
Visiting Scientist, Haematological Malignancies Lab (PI – Rafael Fonseca) Mayo Clinic Scottsdale, Arizona, USA. 2004 – 2007
Associate Consultant, Department of Haematology, National University Hospital, Singapore 2004 – 2006
Registrar, Department of Haematology, National University Hospital, Singapore 2001 – 2004

ZHOU Jianbiao

MD, PhD Senior Research Scientist

Applying system biology, including microarray, shRNA library, NGS, proteomics, animal models to investigate leukeomogensis and leukemia stem cells (CSCs), and to discover novel therapy.

YAN Junli

PhD Senior Research Scientist

Research is concentrating on the epigenetic regulator and non-coding RNAs in natural killer /T-cell lymphoma and acute lymphoblastic leukemia.

XIE Zhigang

PhD Research Scientist

MMSET protein is universally over-expressed in t(4;14) multiple myeloma. My research is focus on the identification of the critical protein partners of MMSET and elucidation of the downstream targets of MMSET.

CHUNG Tae-Hoon

PhD Research Fellow

Computational biologist; interested in genomic abnormalities, epigenetic changes as constitutive framework for cancer phenotypes; also interested in delivering gene expression study benefits to clinical patient care.

Nurulhuda MUSTAFA

PhD Research Fellow

Currently exploring novel therapeutics for multiple myeloma in the context of the role of pro-/-anti apoptotic proteins in the progression of the disease.

Phyllis CHONG Shu Yun

PhD Research Fellow

Global discovery of dysregulated protein expression and phosphorylation networks identifies Leo1 as the key substrate of PRL-3 phosphatase in AML.

TEOH Phaik Ju

PhD Research Fellow

Myeloma patients harbouring p53 hemizygous deletion have very poor prognosis. This study aims to investigate the systemic effects of p53 abnormalities on its pathway and its role in disease progression.

CHOOI Jing Yuan

Research Assistant

Determine protein partners of MMSET in t(4;14) multiple myeloma and functional pathways that contribute to the disease.

LI Boheng

Research Assistant

Role of EZH2 in natural killer/T cell lymphoma.

LIN Baohong

Research Assistant

Functional study of miRNAs in NK-T cell lymphoma and acute myeloid leukemia.

Muhamad Irfan Bin AZAMAN

Laboratory Executive

Explore potential mechanisms and downstream targets of MMSET isoforms in Multiple Myeloma.

LEE Pei Tsung

Laboratory Executive

To study oncogenic epigenetic modifier and the potential targeting strategy in lymphoma.

NEE Huey Fang Adina

Laboratory Executive

Preclinical studies to the test the efficacy of Daratumumab as a potential therapeutic on haematological cancers.

Yvonne NG

Laboratory Executive

Generating resistance cell line to understand the mechanism of drug resistance in patients and carrying out immunoprecipitation to identify PRL-3 targets.

QUAH Yiying Jessie

Laboratory Executive

Understanding the molecular mechanisms of novel therapy in acute myeloid leukemia for biomarker development.

Sabrina TOH

Laboratory Executive

Using molecular approaches to study the oncological role of PRL3 in Leukemia and to investigate Leukemogenesis in mice models.

NUS YLL SOM Outstanding Researcher of the Year Award 2017
NMRC Senior Translational (STaR) Research Award 2017
26th Seah Cheng Siang Memorial Lecture 2016
NMEA National Outstanding Clinician-Scientist Award 2016
NMRC Clinician Scientist (Senior) Award 2012
Chua Hua Toh Memorial Gold Medal (Best Graduate Thesis in
Life Science)
2011
NUS Young Researcher Award 2011
YLL SOM Faculty Outstanding Researcher Award (Young
Researcher Category)
2010
JCI The Outstanding Young Persons (TOYP) Award 2009
NMRC Clinician Scientist (INV) Award 2008
Celgene Future Leaders in Haematology Award 2007