Biomarkers Research Group

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OVERVIEW
Centre for Medical Proteomics – CMedPro    
Proteins and associated molecules that enable cell metabolism represent the highest form of gene expression, and they also characterise cells and tissues in health and disease (Figure 1). Proteomics is one of the three corner stones of Personalised Medicine. The primary objective of CMedPro as part of SERI is to discover biomarkers of disease that can be used clinically for screening, the diagnosis of disease and the response to treatment. We will work primarily in understanding ophthalmic diseases, but we will also collaborate and provide proteomic and metabolomic analysis services outside of SERI.

Quantified biomarkers are used in individual patients for personalised medicine as aids to diagnosis and to evaluate the response to treatment. CMedPro has broad proteomics and metabolomic capabilities, offering analysis for small and large-scale studies, including clinical trials, as well as assistance in experimental design. Our instrumentation provides rapid throughput and high sensitivity. Furthermore, the Centre has quantitative capabilities, including iTRAQ for discovery proteomics and SWATH and MRM for absolute quantitation. As seen in our recent (4) paper, the tear proteome includes about 1300 identifiable proteins. This past year, we have published the first major review of tear proteomics (3). We can provide more detailed explanations of disease processes with a more physiological insight at the cellular level by understanding metabolic changes within the cell (5).

With our platform technology, we have developed clinically useful biomarkers for dry eye, keratoconus, and thyroid eye disease. Biomarkers are becoming increasingly useful in pharmaceutical development and are also reaching clinical use. They would decrease time and costs for diagnosis and determining the response to treatment. This year, we have added a new instrument, the Shimadzu 8040, which will increase throughput for small molecule services, including MRM. This will be particularly useful for those needing to examine protein binding or drug half-life in their tissues or blood.

PROJECTS
Biomarker Development:
Biomarkers (Figure 2) are a key component of the emphasis on personalised medicine and provide the basis for patient stratification.

A – Discovery – very important as this first step determines which biomarkers are considered for further work and analysis. This is a research project with needed quantitation and associated low throughput.

1-Platforms-mass spectrometry, sequencing etc.

B – Verification – Necessary step to select the most valid biomarkers.

C – Validation – Ultimately the biomarkers from “B” must be validated across a large number of samples and conditions. This is standardised and quantitative.

Instrumentaton:
strumentation:Dionex Ultimate 3000 nanoLC

AB SCIEX 5600 TripleTOF Mass Spectrometer

Shimadzu LCMS-8040

Services:
a-Discovery and shotgun proteomics-iTRAQ

b-Biomarker candidate validation

c-Quantitative evaluation: MRM, SWATH

d-Other types of analyses-phosphoprotein and metabolomics

e-Analysis of bands extracted from 1 and 2-D gels

Costs:
Depends on the goals of the research project.

PUBLICATIONS

1. Proteomic Analysis Revealed the Altered Tear Protein Profile in a Rabbit Model of Sjögren’s Syndrome-Associated Dry Eye. Zhou L, Wei R, Zhao P, Koh SK, Beuerman RW, Ding C.,Proteomics. 2013 Jun 3.

2. Quantitative proteomic analysis of N-linked glycoproteins in human tear fluid. Zhou L, Beuerman RW., Methods Mol Biol. 2013;951:297-306.

3. Tear analysis in ocular surface diseases. Zhou L, Beuerman RW., Prog Retin Eye Res. 2012 Nov;31(6):527-50.

4. In-depth analysis of the human tear proteome. Zhou L, Zhao SZ, Koh SK, Chen L, Vaz C, Tanavde V, Li XR, Beuerman RW. J Proteomics. 2012 Jul 16;75(13):3877-85.

5. Global metabonomic and proteomic analysis of human conjunctival epithelial cells (IOBA-NHC) in response to hyperosmotic stress. Chen L, Li J, Guo T, Ghosh S, Koh SK, Tian D, Zhang L, Jia D, Beuerman RW, Aebersold R, Chan EC, Zhou L. J Proteome Res. 2015 Sep 4; 14(9): 3982-95.

6. Characterization of the human tear metabolome by LC-MS/MS. Chen L, Zhou L, Chan EC, Neo J, Beuerman RW. J Proteome Res. 2011 Oct 7;10(10):4876-82.

MEMBERS
Head: Prof Roger Beuerman

Key Personnel:
Dr Zhou Lei, Head of Mass Spectrometry Lab;

Siew Kwan-BS, Mass Spectrometry Technician;

Liyan Chen, MS, Proteomics Analyst

Collaborators:
Dr. C. Ding, Dept. of Cell and Neurobiology, Keck School of Medicine, University of Southern California, USA

A/P Eric Chan, Dept. of Pharmacy, NUS;

Dr. Hannu Uusitalo, Chairman Department of Ophthalmology

Professor Rudi Aebersold, University of Tampere Medical School, Finland

Contact Us: Prof Roger W. Beuerman at roger.wilmer.beuerman@seri.com.sg