Translational Biomedical Proteomics
                       
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  Jayantha GUNARATNE  
  Lab Location: #7-12

email:
jayanthag@imcb.a-star.edu.sg
tel: 65869689
 
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  Key Publications  
 


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

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. (2015)
ELABELA Is an Endogenous Growth Factor that Sustains hESC Self-Renewal via the PI3K/AKT Pathway
Cell Stem Cell 17(4):435-47

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(15):13539-49.

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

Alli Shaik, A, Wee, S, Li RH, Li, 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, Shaik, AA, 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

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

Coffill, R C, Muller, PA, Oh, H K, Neo, S P, Hogue, KA, Cheok, CF, Vousden, KH, Lane, DP, Blackstock, W P and Gunaratne, J (2012)
Mutant p53 interactome identifies nardilysin as a p53R273H-specific binding partner that promotes invasion
EMBO Reports 13:638-44

Swa, H L, Blackstock W, Lim, L and 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

 
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    Jayantha GUNARATNE
 


Jayantha Gunaratne obtained his Ph.D. (2003) from Tokyo Institute of Technology, Japan where he worked on the biochemical characterization of bioactive glycoproteins using chromatography, mass spectrometry and NMR-based approaches. In 2004, he joined Scripps Institution, University of California San Diego (UCSD) as a research scholar to pursue his postdoctoral work. In 2007, he moved to Singapore as a founder member of the Mass Spectrometry and Systems Biology Laboratory in IMCB and led quantitative proteomics -based biology research projects. Since 2011 June, he heads the IMCB Translational Biomedical Proteomics Group. He is currently a Principal Investigator in IMCB, and holds adjunct positions in Yong Loo Lin School of Medicine National University of Singapore (Associate Professor) and Imperial College London - Nanyang Technological University Singapore.

       
    Quantitative Mass Spectrometry & Translational Proteomics
   


Quantitative mass spectrometry (qMS)-based proteomics is a core technology in modern biology complementing the plethora of molecular biology methods. A key advantage lies in the simultaneous tracking of the abundance of thousands of proteins and in following, the assembly and disassembly of protein complexes – the fundamental effectors of living organisms. In combination with advanced computational biology, this technology allows system-wide characterization of dynamic biological events such as carcinogenesis, infection and inflammation at the levels of protein–protein interactions, protein expression variations, post-translational modifications and protein degradation.

Among several MS-based proteomics approaches, our lab employs bottom-up proteomics, also known as shotgun proteomics. This technology platform has established its niche in the crucial and imperative processing workflow of screening using discovery quantitative proteomics under data dependent acquisition (DDA) mode and validation/hypothesis testing using targeted proteomics strategies.

Our laboratory is equipped with core components required for bottom-up proteomics including high resolution LC-MS instrumentation, modern biochemical approaches and advanced MS-based computational pipeline. Fully established workflows for metabolic (SILAC) and chemical labelling (TMT/dimethyl labeling etc.), as well as label-free quantification (LFQ) are employed for quantification of global proteome/post-translational modifications (PTM) in any kind of biological samples including cell lines, tissues and biofluids. For detection of low abundant protein species that are mostly clinically relevant and to achieve high reproducibility and accuracy in quantification, we have also established targeted proteomics pipeline and engaged next generation Data Independent Acquisition (DIA) technologies for high-throughput data exploration in hypothesis testing and validation phase.  These establishments coupled with computational biology enable us to execute any systems biology-based and translational clinical research projects for diagnostics and therapeutics in human diseases.

 
 
Research: The group currently focuses on two main research themes

  (1)
Mode-of-action of small molecule (SM) drugs:

It is indisputable that detailed knowledge at the molecular level of the target and off-target interactions of a drug is important. Drug target identification has remained a bottleneck despite the development of many advanced methodologies to discover protein targets of SM drugs.

We use and develop qMS–based strategies to elucidate mode-of-action of selected anti-cancer SMs of diverse chemical nature. Bioorthogonal/click-chemistry-coupled chemical proteomics, thermal shift profiling as well as system-wide proteome/PTM using SILAC-based qMS are some approaches used for the identification of direct and off-protein targets and elucidation of molecular mechanisms. Integrative protein network analysis is carried out for the deduction of possible mode-of-action.
   
  (2)
Deregulated hubs of protein networks in human diseases:

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 modern MS strategies to capture positive protein markers which are involved in deregulating molecular pathways in various cancers. We screen clinical samples and cell lines using DDA-based chemical labeling and LFQ approaches to achieve in-depth proteome profiling to identify deregulated protein clusters distinct to the cancer. These strategies are coupled with advanced computational tools for reconstruction of biological networks to reveal druggable targets and other ‘extended’ prognostic markers that are clinically relevant.