Jayantha GUNARATNE

Translational Biomedical Proteomics

Profile

Jayantha GUNARATNE
Lab Location: #7-12   Email: jayanthag@imcb.a-star.edu.sg   Tel: 65869689

Jayantha Gunaratne obtained his Ph.D. in Biosciences from Tokyo Institute of Technology, Japan in 2003 where he received training on gas and liquid chromatography, mass spectrometry and NMR technologies. He has received several scientific awards including the prestigious Japanese Government International Graduate Scholarship, and Yasumasu and Inoue Foundation Young Scientist awards in Japan (2001 & 2003). In 2004, he was offered a postgraduate research scholar position at Scripps Institution, University of California San Diego, USA to pursue his postdoctoral work on genome annotation, proteomics and biochemical analysis in developmental biology. In 2007, he moved to Singapore as a founder member of the Mass Spectrometry and Systems Biology Laboratory in IMCB and pioneered the establishment of high-resolution advanced quantitative proteomics technology in Singapore. He is currently a Principal Investigator heading translational biomedical proteomics research in IMCB and also an adjunct Associate Professor in Yong Loo Lin School of Medicine, National University of Singapore.

Research

Proteomics Mass Spectrometry in Health and Diseases

Proteomics mass spectrometry (MS) is the forefront technology for studying proteotype, the state of a proteome associated with a specific phenotype. Over the last decade, we have fully established this powerful technology including strategized pipelines for proteotype studies through proteome profiling (Swa et al. 2012 & 2015, Gunaratne et al. 2013, Alli Shaik et al. 2014, Ng et al. 2015), interactomes (Gunaratne et al. 2011, Coffill et al. 2012, Dong et al. 2016) and post-translational modifications (Alli Shaik et al. 2016 & 2017, Ho et al. 2015). Apart from discovery proteomics, our group also focuses on developing targeted proteomics applications (Wee et al. 2019). Currently we hold several translational and clinical research projects, and collaborate with international and national institutes, government agencies, hospitals and industry partners.

Our group focuses on 2 main research themes: 

1. Disease biomarker discovery:  Proteins orchestrate key biological events within the cell and any aberrant wiring in the complex protein-protein network often manifests itself in pathological conditions such as cancer. Identification of unique molecular signatures from haywire protein networks is important in early detection, precise diagnostics and targeted therapeutics of several disease conditions. Our group employs deep proteomics strategies to capture protein markers in dysregulated molecular pathways. We screen clinical samples including biofluids to identify deregulated protein clusters and subject them to advanced computational tools for reconstruction of biological networks to reveal druggable targets and prognostic markers that are clinically relevant. One of our main research interests is to dissect breast cancer heterogeneity and develop liquid biopsy approaches for early diagnosis, prognosis and patient stratifications. The other ongoing research projects in this line include chronic kidney disease (CKD), hepatitis B viral (HBV) infection, diabetic retinopathy (DR) and heart failure (HF) where our group leads in biomarker discovery and protein therapeutic target identification. We have already identified promising biomarker panels for bladder cancer and CKD (urine), breast cancer (tissue) as well as DR, HF and HBV (blood). In addition to conventional biochemical tools for biomarker validation, we also establish and use in-house targeted MS assays as part of the work under our technology development theme.


2. Technology development: Applications of proteomics MS have traditionally been focusing on expression and post-translational (e.g. phosphorylation, acetylation and ubiquitination) profiling. In our group, we push the limits of this state-of-art MS technology in interrogating, tracking and validating molecular events. One such clinical application is the prototype we developed for single-shot flavivirus diagnosis (Wee et al. 2019).  Other technology development projects include novel SWATH MS applications for tracking signalling pathways (in collaboration with SCIEX), development of novel screening tools (in collaboration with SFA), and biochemical approaches and advanced computational tools for next generation biomarker discovery.



Staff

Department: Jayantha GUNARATNE

Name: Siok Ghee LER

Designation: Senior Research Associate

Email: sgler@imcb.a-star.edu.sg


Name: Asfa ALLI SHAIK

Designation: Senior Research Fellow

Email: asfaas@imcb.a-star.edu.sg


Name: Qifeng LIN

Designation: Research Fellow

Email: qflin@imcb.a-star.edu.sg


Name: Zijie LIM

Designation: NUS-IMCB Collaborator

Email: mdclimz@nus.edu.sg


Name: Claire Lee Foon SWA

Designation: Senior Research Fellow

Email: swalf@imcb.a-star.edu.sg


Name: Suat Peng NEO

Designation: Senior Research Officer

Email: neosp@imcb.a-star.edu.sg


Name: Esther Wee Ling CHUA

Designation: Research Officer

Email: chuawl1@imcb.a-star.edu.sg


Name: Jared Guan Xian LIM

Designation: Research Officer

Email: limgxj@imcb.a-star.edu.sg


Name: Sheena WEE

Designation: Research Scientist

Email: swee@imcb.a-star.edu.sg


Name: Max KOSOK

Designation: SINGA Student

Email: maxk@student.imcb.a-star.edu.sg


Publications

2019

Wee S, Alli-Shaik A, Kek R, Swa HLF, Tien WP, Lim VW, Leo YS, Ng LC, Hapuarachchi HC, Gunaratne J. (2019)
Multiplex targeted mass spectrometry assay for one-shot flavivirus diagnosis.
Proc Natl Acad Sci U S A. 116:6754-6759
News release: https://www.360dx.com/mass-spec/proteomic-test-diagnose-differentiate-zika-dengue-developed-astar-team#.XJrqvVUzZhE

Lim JP, Nair S, Shyamasundar S, Chua PJ, Muniasamy U, Matsumoto K, Gunaratne J*, Bay BH.* (2019) *co-corresponding authors

Silencing Y-box binding protein-1 inhibits triple-negative breast cancer cell invasiveness via regulation of MMP1 and beta-catenin expression.

Cancer Lett. 452:119-131

 

Liu Z, Liow SS, Lai, Alli-Shaik A, Holder GE, Parikh BH, Krishnakumar S, Li Z, Tan MJ, Gunaratne J, Barathi VA, Hunziker W, Lakshminarayanan R, Tan CWT, Chee CK, Zhao P, Lingam G, Loh XJ & Su X. (2019)

Retinal-detachment repair and vitreous-like-body reformation via a thermogelling polymer endotamponade.

Nat Biomed Eng. doi: 10.1038/s41551-019-0382-7

 

2018

Chong PSY, Zhou J, Chooi JY, Chan ZL, Toh SHM, Tan TZ, Wee S, Gunaratne J, Zeng Q, Chng WJ. (2018)

Non-canonical activation of β-catenin by PRL-3 phosphatase in acute myeloid leukemia.

Oncogene. 38:1508-1519

 

Chen J, Rajasekaran M, Xia H, Kong SN, Deivasigamani A, Sekar K, Gao H, Swa HL, Gunaratne J, Ooi LL, Xie T, Hong W, Hui KM.

CDK1-mediated BCL9 phosphorylation inhibits clathrin to promote mitotic Wnt signalling.

EMBO J. 15;37(20).

 

Koh CWQ, Goh YT, Toh JDW, Neo SP, Ng SB, Gunaratne J, Gao YG, Quake SR, Burkholder WF, Goh WSS. (2019)

Single-nucleotide-resolution sequencing of human N6-methyldeoxyadenosine reveals strand-asymmetric clusters associated with SSBP1 on the mitochondrial genome.

Nucleic Acids Res. 46:11659-11670.

 

Jakhar R, Luijten MNH, Wong AXF, Cheng B, Guo K, Neo SP, Au B, Kulkarni M, Lim KJ, Maimaiti J, Chong HC, Lim EH, Tan TBK, Ong KW, Sim Y, Wong JSL, Khoo JBK, Ho JTS, Chua BT, Sinha I, Wang X, Connolly JE, Gunaratne J, Crasta KC.

Autophagy Governs Protumorigenic Effects of Mitotic Slippage-induced Senescence.

Mol Cancer Res. 16:1625-1640.

 

Liao KC, Chuo V, Ng WC, Neo SP, Pompon J, Gunaratne J, Ooi EE, Garcia-Blanco MA.

Identification and characterization of host proteins bound to dengue virus 3' UTR reveal an antiviral role for quaking proteins.

RNA. 24:803-814

 

2017

Alli-Shaik A, Wee S, Lim LHK, Gunaratne J. (2017)

Phosphoproteomics reveals network rewiring to a pro-adhesion state in annexin-1-deficient mammary epithelial cells.

Breast Cancer Res. 219:132.

 

Boopathy GTK, Lynn JLS, Wee S, Gunaratne J, Hong W. (2017)

Phosphorylation of Mig6 negatively regulates the ubiquitination and degradation of EGFR mutants in lung adenocarcinoma cell lines.

Cell Signal. 43:21-31.

 

Tan KK, Ler SG, Gunaratne J, Bay BH, Ponnampalam G. (2017)

In vitro cytotoxicity of L-amino acid oxidase from the venom of Crotalus mitchellii pyrrhus.

Toxicon. 139:20-30.

 

Toloczko A, Guo F, Yuen HF, Wen Q, Wood SA, Ong YS, Chan PY, Shaik AA, Gunaratne J, Dunne MJ, Hong W, Chan SW. (2017)

Deubiquitinating Enzyme USP9X Suppresses Tumor Growth via LATS Kinase and Core Components of the Hippo Pathway.

Cancer Res. 77:4921-4933.

 

Lim JP, Shyamasundar S, Gunaratne J, Scully OJ, Matsumoto K, Bay BH. (2017) 
YBX1 gene silencing inhibits migratory and invasive potential via CORO1C in breast cancer in vitro.
BMC Cancer. 17:201

 

Singaravelu P, Lee WL, Wee S, Ghoshdastider U, Ding K, Gunaratne J, Grimes JM, Swaminathan K, Robinson RC.(2017) 
Yersinia Effector Protein YopO mediated Phosphorylation of Host Gelsolin Causes Calcium-Independent Activation leading to Disruption of Actin Dynamics.
J Biol Chem. 292(19):8092-8100

 

Lee WL, Singaravelu P, Wee S, Xue B, Ang KC, Gunaratne J, Grimes JM, Swaminathan K, Robinson RC. (2017) 
Mechanisms of Yersinia YopO kinase substrate specificity. 
Sci Rep. 7:39998.

 

2016

Asfa AS, Qiu B, Wee S, Choi H, Gunaratne J*, Tergaonkar V* (2016) * co-corresponding authors

Phosphoprotein network analysis of white adipose tissues unveils deregulated pathways in response to high-fat diet 
Sci Rep. 6:25844

 

Bararia D, Kwok HS, Welner RS, Numata A, Sárosi MB, Yang H, Wee S, Tschuri S, Ray D, Weigert O, Levantini E, Ebralidze AK, Gunaratne J, Tenen DG (2016)  
Acetylation of C/EBPα inhibits its granulopoietic function
Nat Commun.7:10968

 

Ward AM, Calvert ME, Read LR, Kang S, Levitt BE, Dimopoulos G, Bradrick SS, Gunaratne J, Garcia-Blanco MA. (2016) 
The Golgi associated ERI3 is a Flavivirus host factor. 
Sci Rep. 6:34379

Diril MK, Bisteau X, Kitagawa M, Caldez MJ, Wee S, Gunaratne J, Lee SH, Kaldis P. (2016)
Loss of the Greatwall Kinase Weakens the Spindle Assembly Checkpoint. 
PLoS Genet. 12(9):e1006310

Dong JM, Tay FP, Swa HL, Gunaratne J, Leung T, Burke B, Manser E. (2016)  
Proximity biotinylation provides insight into the molecular composition of focal adhesions at the nanometer scale. 
Sci Signal. 9(432):rs4

Brichkina A, Nguyen NT, Baskar R, Wee S, Gunaratne J, Robinson RC, Bulavin DV. (2016) 
Proline isomerisation as a novel regulatory mechanism for p38MAPK activation and functions. 
Cell Death Differ. 23:1592-601

2015

Ng CT, Yung LY, Swa HL, Poh, RW, Gunaratne J*, Bay BH* (2015) *co-corresponding author

Altered protein expression profile associated with phenotypic changes in lung fibroblasts co-cultured with gold nanoparticle-treated small airway epithelial cells.
Biomaterials 39:31-8.

 

Kumar P, Nandi S, Tan TZ, Ler SG, Chia KS, Lim WY, Bütow Z, Vordos D, De laTaille A, Al-Haddawi M, Raida M, Beyer B, Ricci E, Colombel M, Chong TW, Chiong E, Soo R, Park MK, Ha HK*, Gunaratne J*, Thiery JP*.(2015) *co-senior authors
Highly sensitive and specific novel biomarkers for the diagnosis of transitional bladder carcinoma. 
Oncotarget
. 6:13539-49.

 

Ho L, Tan SY, Wee S, Wu Y, Tan SJ, Ramakrishna NB, Chng SC, Nama S, Sczerbineska I, Chan W, Avery S, Tsuneyoshi N, Ng HH, Gunaratne J, Dunn NR, Reversade B. 
ELABELA Is an Endogenous Growth Factor that Sustains hESC Self-Renewal via the PI3K/AKT Pathway (2015). 
Cell Stem Cell 17:435-47

Yang BX, El Farran CA, Guo HC, Yu T, Fang HT, Wang HF, Schlesinger S, Seah YF, Goh GY, Neo SP, Li Y, Lorincz MC, Tergaonkar V, Lim TM, Chen L, Gunaratne J, Collins JJ, Goff SP, Daley GQ, Li H, Bard FA, Loh YH. 
Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells (2015) 
Cell.
 163:230-45

Lee J, Wee S, Gunaratne J, Chua RJ, Smith RA, Ling L, Fernig DG, Swaminathan K, Nurcombe V, Cool SM. Structural determinants of heparin-transforming growth factor-β1 interactions and their effects on signalling (2015) 
Glycobiology 25:149

Manokaran G, Finol E, Wang C, Gunaratne J, Bahl J, Ong EZ, Tan HC, Sessions OM, Ward AM, Gubler DJ, Harris E, Garcia-Blanco MA, Ooi EE. (2015)
Dengue subgenomic RNA binds TRIM25 to inhibit interferon expression for epidemiological fitness. 
Science. 350:217-21

Koh HW, Swa HL, Fermin D, Ler SG, Gunaratne J, Choi H. (2015) 
EBprot: Statistical Analysis of Labeling-based Quantitative Proteomics Data. 
Proteomics 15:2580-91

Tan CL, Teissier S, Gunaratne J, Quek LS, Bellanger S. (2015) 
Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy. 
Cell Cycle.
 14:1459-70.

Chakraborty S, Lakshmanan M, Swa H, Chen J,  Zhang X, Ong YH, Loo LS, Akıncılar S, Gunaratne J, Tergaonkar V, Hui K, Hong W(2015)  
An oncogenic role of Agrin in regulating focal adhesion integrity in Hepatocellular carcinoma. 
Nat Commun. 6:6184


2014

Alli Shaik A, Wee S, Li RH, Li Z, Carney TJ, Mathavan S, Gunaratne J (2014) 

Functional Mapping of the Zebrafish Early Embryo Proteome and Transcriptome. 
J Proteome Res. 13:5536-50

Swa HL, Alli Shaik A, Lim, LH., Gunaratne J (2014) 
Mass spectrometry-based quantitative proteomics and integrative network analysis accentuates modulating roles of Annexin-1 in mammary tumorigenesis. 
Proteomics 15:408-18

 

Ward AM, Gunaratne J, Garcia-Blanco MA (2014) 
Identification of dengue RNA binding proteins using RNA chromatography and quantitative mass spectrometry 
Methods Mol Biol:1138:253-70

 

Zhang W, Neo SP, Gunaratne J, Poulsen A, Boping L, Ong EH, Sangthongpitag K, Pendharkar V, Hill J, Cohen SM (2014) 
Feedback regulation on PTEN/AKT pathway by the ER stress kinase PERK mediated by interaction with the Vault complex. 
Cell Signal. 27:436-42

Qiu B, Shi X, Wong ET, Lim J, Bezzi M, Low D, Zhou Q, Akıncılar SC, Lakshmanan M,Swa HL, Tham JM, Gunaratne J, Cheng KK, Hong W, Lam KS, Ikawa M, Guccione E, Xu A ,Han W, Tergaonkar V. (2014) 
NUCKS is a positive transcriptional regulator of insulin signalling. 
Cell Rep 7:1876-86

Huang YF, Wee S, Gunaratne J, Lane DP, Bulavin DV (2014)
Isg15 controls p53 stability and functions 
Cell Cycle 13:2200-10

 

2013
 

Gunaratne J, Schmidt A, Quandt A, Neo SP, Sarac OS, Gracia T, Loguercio S, Ahrne E, Li Hai Xia R, Tan KH, Loessner C, Bahler J, Beyer A, Blackstock W, Aebersold R (2013) 
Extensive Mass Spectrometry-Based Analysis of the Fission Yeast Proteome: The S pombe PeptideAtlas 
Mol Cell Proteomics 12:1741-51

 

Zhang W, Hietakangas V, Wee S, Lim R, Gunaratne J, Cohen SM,(2013) 
ER stress potentiates insulin resistance through PERK-mediated FOXO phosphorylation 
Genes Dev 27:441-9

Bard-Chapeau EA, Gunaratne J, Kumar P, Chua BQ, Muller J, Bard FA, Blackstock W, Copeland NG, Jenkins NA (2013) 
EVI1 oncoprotein interacts with a large and complex network of proteins and integrates signals through protein phosphorylation 
Proc Natl Acad Sci U S A. 110:E2885-94

Xie Z, Gunaratne J, Cheong LL, Liu SC, Koh TL, Huang G, Blackstock WP, Chng WJ (2013) 
Plasma membrane proteomics identifies biomarkers associated with MMSET overexpression in T(4;14) multiple myeloma 
Oncotarget  4:1008-18

 

Lai D, Tan CL, Gunaratne J, Quek LS, Nei W, Thierry F, Bellanger S (2013) 
Localization of HPV-18 E2 at Mitochondrial Membranes Induces ROS Release and Modulates Host Cell Metabolism 
PLoS ONE 8: e75625


2012 

Coffill RC, Muller PA, Oh HK, Neo SP, Hogue KA, Cheok CF, Vousden KH,  Lane DP, Blackstock WP, Gunaratne J (2012) 
Mutant p53 interactome identifies nardilysin as a p53R273H-specific binding partner that promotes invasion 
EMBO Reports 13:638-44

Swa, HL, Blackstock W, Lim L, Gunaratne J (2012) 
Quantitative proteomics profiling of murine mammary gland cells unravels impact of Annexin-1 on DNA damage, cell adhesion and migration 
Mol Cell Proteomics 11:381-93

Lößner C, Wee S, Ler SG, Blackstock W, Gunaratne J (2012) 
Analysis of the zebrafish embryo proteome using a multiple fractionation approach followed by tandem mass spectrometry 
Proteomics 
12:1879-82

Khong JH, Zhang T, Gunaratne J, Blackstock W, Surana U (2012) 
"Reductional anaphase" in replication-defective cells is caused by ubiquitin-conjugating enzyme Cdc34-mediated deregulation of the spindle 
Cell Cycle 11:2896-910

Chuang LSH, Lai LK, Murata-Hori M, Yamada A, Hoi-Yeung Li, Gunaratne J, Ito Y (2012)
RUNX3 interactome reveals novel centrosomal targeting of RUNX family of transcription factors 
Cell Cycle 11:1938-47

Tan CL, Gunaratne J,  Lai D, Carthagena  L, Wang Q, Xue YC, Quek LH, Bachelerie F, Thierry F, Bellanger S (2012) 
HPV-18 E2^E4 chimera: 2 new spliced transcripts and proteins induced by keratinocyte differentiation 
Virology
 429:47-56

Bard-Chapeau EA, Jeyakani J, Kok C, Muller J, Chua BQ, Gunaratne J, Batagov A, Jenjaroenpun P, Kuznetsov V, Wei C, D'Andrea R, Bourque G, Jenkins NA, Copeland NG (2012) 
EVI1 regulates multiple cellular processes important for cancer and is a synergistic partner for FOS in invasive tumors 
Proc Natl Acad Sci U S A. 109: 2168-73

 

Migliori V, Muller J, Phalke S, Low D, Bezzi M, Mok WC, Sahu KS, Gunaratne J, Capasso P, Bassi C, Cecatiello V, De Marco A, Blackstock W, Kuznetsov V, Amati B, Mapelli M, Guccione E (2012) 
Symmetric dimethylation of H3R2 is a newly identified histone mark that supports euchromatin maintenance 
Nat Struct & Mol Biol 19:136-44

2011 & before

Lößner C, Blackstock W, Gunaratne J (2011) 
Enhanced performance of Pulsed Q Collision Induced Dissociation-based peptide identification on a dual-pressure linear ion trap 
J Am Soc Mass Spectrom 23:186-89

Ward AM, Bidet K, Yinglin A, Ler SG, Hogue KA, Blackstock WP, Gunaratne J, Garcia-Blanco M (2011) 
Quantitative Mass Spectrometry of DENV-2 RNA-Interacting Proteins Reveals that the DEAD-box RNA helicase DDX6 Binds the DB1 and DB2 3’ UTR Structures 
RNA Biology 8:1173-86

Gunaratne J, Goh MX,  Swa H L , Lee FY, Sanford E, Wong LM, Hogue K, Blackstock W, Okumura K (2011) 
The protein interactions of PTEN and its cancer-associated G20E mutant compared by SILAC-based parallel affinity purification and mass spectrometry 
J Biol Chem 286:18093-103

Chan SW, Lim CJ, Huang C, Chong YF, Gunaratne HJ, Hogue K, Blackstock W, Harvey KF, Hong W (2010) 
WW Domain-mediated Interaction with Wbp2 is Important for Oncogenic Property of TAZ 
Oncogene 30:600-10

 

For publications before joining IMCB, please visit Pubmed (keyword: Gunaratne H.J.)

Patent filed:

Biomarker discovery in the urine of early stage bladder cancer patients. Europe Patent # 3066474, China Patent Publication # CN 105899953B, International patent application # IMC/P/07991/01/PCT. Licensed in 2018, # PC/SW/2934/0518/ETPL-IMCB.

 

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