CHNG Wee Joo

Deputy Director & Senior Principal Investigator, Cancer Science Institute of Singapore, NUS
Provost’s Chair & 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)

mdccwj[at]nus.edu.sg

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 as well as molecular abnormalities in these malignancies, therby providing insights into disease pathogenesis and biology, and serve as potential targets for therapy.

Research

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 regard, 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 defects. 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 unravelled 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 activations are due to downregulation of regulating miRNAs. The downregulation of these miRNAs are mediated by EBV infection or MYC activation. We have also identified certain markers that are universally over-expressed in NKTL and may serve as novel therapeutic targets.

 

Lab Members

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-? 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.

Honors & Awards

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