In utero environment and early life experience has been shown to have epigenetic consequences which affect susceptibility to complex diseases in later life. We are focused on a mechanistic understanding of these processes and discovering epigenetic biomarkers that can be used to assess the efficacy of lifestyle, nutritional or pharmacological intervention.

SICS has embarked with collaborators on large, longitudinal and extremely well controlled clinical studies and equally extensive studies in model organisms. In collaboration with the genomics and cell biology groups we are analyzing genomics data to formulate biological hypotheses and leading further studies to validate the mechanisms and biomarker signatures.

We have expertise in array and NGS data processing and integration.  We specialise in making biological sense of complex datasets.

Main Projects:

1. Analysis and integration of genomics data from biological samples collected in large translational research projects in Singapore and collaborator sites.  The aim is to discover epigenetic modifications caused by early environment, which have an impact of disease risk in adulthood.
2. Contribution of persistant epigenetic marks to metabolic and cognitive disease and implications for human therapeutics

Other projects:

1. Impact of genotype and methylome on the transcriptome: comparsion of methylome and transcriptomics data from different profiling technologies and across classes of CpG sites.
2. Stability of the epigenome across individuals and tissues and measurement in clinic.
3. Molecular classification of individuals based on RNA profiles in umbilical cord tissue, correlates to clinical data.
4. Molecular evolution of biological pathways implicated in metabolic and cognitive disease in humans and macaques.

Pan H, Chen L, Dogra S, Ling Teh A, Tan JH, Lim YI, Lim YC, Jin S, Lee YK, Ng PY, Ong ML, Barton S, Chong YS, Meaney MJ, Gluckman PD, Stunkel W, Ding C, Holbrook JD (2012) Measuring the methylome in clinical samples – improved processing of the infiniumHD 450K array. Epigenetics 7(10)

Stünkel W, Pan H, Chew R, Tng E, Tan JH, Joseph R, Cheong C, Chen L, Lee YS,  Chong YS, Mei SS,  Meaney MJ, Kwek K, Sheppard AM, Gluckman PD, Holbrook JD (2012) Transcriptome changes affecting hedgehog and cytokine signalling in the umbilical cord in late pregnancy: potential implications for disease risk. PLoS One. 7(7):e39744.

Sandanaraj E and Holbrook JD (2012) Gastric Cancer, oncogenes and targeted therapies. Gastric & Breast Cancer international 11(3): XXX

Yeo C, Ng F, Chai C, Tan J, Koh G, Chong YK, Koh L, Foong C, Sandanaraj E, Holbrook JD, Ang BT, Takahashi R, Tang C, Lim KL (2012) Parkin pathway activation mitigates glioma cell proliferation and predicts survival outcome for patients. Cancer Research 72(10):2543-2553

Jing J, Greshock J, Holbrook JD, Gilmartin AG, Zhang X, McNeil E, Conway T, Moy C, Laquerre S, Bachman KE, Wooster R (2012) Comprehensive Predictive Biomarker Analysis for MEK Inhibitor GSK1120212.  Molecular Cancer Therapeutics. 11(3):720-9

Holbrook JD, Parker JS, Gallagher KT, Halsey WS, Hughes AM, Weigman VJ, Lebowitz PF, Kumar R (2011) Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine. Journal of Translational Medicine 9:119 [Highly accessed article]

Sanger G, Holbrook JD, Andrews PL (2011) . The translational value of rodent gastrointestinal functions: a cautionary tale. Trends in Pharmaceutical Sciences 32(7):402-409

Rollins DK and Teh A (2010) An extended data mining method for identifying differentially expressed assay-specific signatures in functional genomic studies BioData mining 3:11

Zhang Y, Italia M, Magid-Slav M, Sethe G, Halsey W, Auger K, Brown J, Holbrook JD (2009) Evolutionary analysis of somatic mutations in cancer cell lines (2010) Molecular Cancer Therapeutics 9(2):279-291 [Selected for Editorial Highlight]

Holbrook JD, Frost C, Zebda N, Spencer JP, Leyland R, Rance KH, Trinh H, Yusaf SP, Courtney N, Luck J, Rhodes A, Modha S, Moore SE, Sanger GJ, Gunthorpe M (2009) Characterisation of 5-HT3C, 5-HT3D and 5-HT3E receptor subunits: evolution, distribution and function. Journal of Neurochemisty 108(2):384-396

Richter MC, Groy AX, Wang D, Lu Q, Holbrook JD, Sarpong MA, Seefeld MA, Smith DM, Laquerre SG, Gilmartin AG (2009) Reassessing IKKe as a Novel Oncology Target, presented at AACR-NCI-EORTC 2009

Papan C and Chen L (2009) Metabolic Fingerprinting Reveals Developmental Regulation of Metabolites During Early Zebrafish Embryonic Development. OMICS, A Journal of Integrative Biology 13(5)

Zhang G, Liu T, Wang Q, Chen L, Ma G and Zhang Z (2009) Mass Spectrometric Detection of Marker Peptides in Tryptic Digest of Gelatin: A New Method to Differentiate between Bovine and Porcine Gelatin, Food Hydrocolloids 23(7): 2001-2007

Vamethevan J, Hasan S, Madsen HA, Kumar V, Word M, Simmons MD, Topp SD, Foord SM, Sanseau P, Emes RD, Yang Z, and Holbrook JD (2008) The role of positive selection in determining the molecular cause of species differences in disease. BMC Evolutionary Biology 8:273 [Highly Accessed Article]

Michel AD, Clay WC, Ng SW, Roman S, Thompson K, Condreay JP, Hall M, Holbrook JD, Livermore D and Senger S (2008) Identification of regions of the P2X7 receptor that contribute to human and rat species differences in antagonist effects. British journal of Pharmacology 155(5):738-751

Olsson C, Holbrook JD, Bompadre G, Jonsson E, Hoyle CH, Sanger GJ, Holmgren S, Andrews PL. (2008) Identification of genes for the ghrelin and motilin receptors and a novel related gene in fish, and stimulation of intestinal motility in zebrafish (Danio rerio) by ghrelin and motilin. Gen Comp Endocrinol. 155(1):217-226

Michel AD, Clay WC, Ng SW, Roman S, Thompson K, Condreay JP, Hall M, Holbrook JD, Livermore D and Senger S (2008) Identification of regions of the P2X7 receptor that contribute to human and rat species differences in antagonist effects. British journal of Pharmacology 155(5):738-751

Chen L (2008) Using Multivariate Curve Resolution to Improve Proteomic Mass Spectra Classification(MCR-marker), Chemometrics and Intelligent Laboratory Systems 94(2): 123-130.

Chen L and Yap Y (2008) Automated Charge State Determination of Complex Isotope-Resolved Mass Spectrometry Using Peak-Target Fourier Transform. Journal of the American Society for Mass Spectrometry 19(1): 46-54

Vamathevan J, Holbrook JD, Emes RD (2007) The Mouse Genome as a Rodent Model in Evolutionary Studies. Encylopedia of Life Sciences DOI: 10.1002/9780470015902.a0020754 Article Online Posting Date: December 21, 2007

Cutler P, Akuffo E, Bodnar W, Briggs D, Davis J, Debouck C, Fox S, Gibson R, Gormley D, Holbrook JD, Hunter J, Kinsey E, Prinjha R, Richardson J, Roses A, Smith M, Tsokanas N, Willé D, Wu W, Yates J, Gloger IS (2007) Proteomic identification and early validation of complement 1 inhibitor and pigment epithelium-derived factor: Two novel biomarkers of Alzheimer's disease in human plasma. Proteomics 2(4):467-477

Campbell SJ, Jiang Y, Davis AEM, Farrands R, Holbrook J, Leppert D, Anthony DC. (2007) Immunomodulatory effects of etanercept in a model of brain injury act through attenuation of the acute-phase response. Journal of Neurochemistry 103 (6):2245-2255

Holbrook JD and Sanseau P (2007) Drug discovery and computational evolutionary analysis Drug Discovery and Computational Evolutionary Analysis. Drug Discovery Today 12(19-20):826-832

Li C, Chen L, Garland M (2007) Synchronicity of Mononuclear and Dinuclear Events in Homogeneous Catalysis Journal of the American Chemical Society 129(43): 13327-13334

Barnes MR, Holbrook J, Feild JA, Searls DB, Sanseau P. (2006) Risk in drug trials. Lancet 368(9554):2205

Stone C., Holbrook J., Madsen H., Modha S., Craig C. (2006) Amplification and sequencing of HIV-1 from Low Viral Load Plasma Samples and Analysis and Interpretation of Sequences Obtained. Poster presented at 4th European Drug Resistance Meeting.

Clay W., Condreaya P., Hall M., Holbrook J.,Livermore D., Michel A., Powell A., Senger S. (2006) Site-directed mutagenesis study of human and rat P2X7 receptors and the effect on ligand activity. Poster presented at European Medicinal Chemistry Conference

Chen L, Sze SK, Yang H (2006) Automated Intensity Descent Algorithm for Efficient Interpretation of Complex High Resolution Mass Spectra. Analytical Chemistry 78: 5006-5018

Gao F, Chen L, Garland M (2006) A new origin for stereo-differentiation in the Orito reaction. Residual chiral induction and enantiomeric excess reversal during piece-wise continuous experiments using a chiral fixed bed reactor.  Journal of Catalyst 238(2):402-111

Hong Pan et.al. (2006) Extracting Information for Meaningful Function Inference Through Text-Mining n Discovering Biomolecular Mechanisms with Computational Biology”, (Eisenhaber eds) Landes Bioscience,

Gill CH, Moore SE, Rance K, Yusaf SP, Courtenay N, Sanger GJ, Holbrook JD, Gunthorpe M (2005) Characterisation of the novel human 5-HT3 receptor subunits (HTR3C-E). Poster presented at the British Pharmacology Society Winter Meeting 2005

Birdsey GM, Lewin J, Holbrook JD, Simpson VR, Cunningham AA, Danpure CJ. (2005) A comparative analysis of the evolutionary relationship between diet and enzyme targeting in bats, marsupials and other mammals. Proc Biol Sci. 22;272(1565):833-40.

Foord SM, Topp SD, Abramo M, Holbrook JD. (2005) New methods for researching accessory proteins. J Mol Neurosci. 26(2-3):265-76.

Bajic VB, Veronika M, Veladandi PS, Meka A, Heng MW, Rajaraman K, Hong Pan, Swarup S (2005) Dragon Plant Biology Explorer. A text-mining tool for integrating associations between genetic and biochemical entities with genome annotation and biochemical terms lists Plant Physiol. 138(4):1914-25.

Tiffin N, Kelso JF, Powell AR, Hong Pan, Bajic VB, Hide WA (2005) Integration of text- and data-mining using ontologies successfully selects disease gene candidates Nucleic Acids Res. 33(5):1544-52.

Tan AH and Hong Pan (2005) Predictive Neural Networks for Gene Expression Data Analysis Neural Networks 18(3): 297-306.

Brooke G, Holbrook JD, Brown MH, Barclay AN. (2004) Human lymphocytes interact directly with CD47 through a novel member of the signal regulatory protein (SIRP) family. J Immunol. 173(4):2562-70.

Holbrook JD and Dingwall C. (2004) Human HtrA proteases. n Handbook of Proteolytic Enzymes, 2 edn (Barrett,A.J., Rawlings,N.D. & Woessner,J.F. eds), p.1476-1480, Elsevier, London

Zhao Y, Gao F, Li Chen L, Garland M (2004) A Chiral Fixed Bed Reactor for Stereoselective Heterogeneous Catalysis: Modification, Regeneration and Multiple Product Synthesis. Journal of Catalyst  221(2): 274-287

Hong Pan, Zuo L, Choudhary V, Zhang Z, Leow SH, Chong FT, Huang Y, Ong VW,Mohanty B, Tan SL, Krishnan SP, Bajic VB (2004) Dragon TF Association Miner: a system for exploring transcription factor associations through text-mining Nucleic Acids Res. 32(Web Server issue):W230-4.

White IR, Man WJ, Bryant D, Bugelski P, Camilleri P, Cutler P, Hayes W, Holbrook JD, Kramer K, Lord PG, Wood J. (2003) Protein expression changes in the Sprague Dawley rat liver proteome following administration of peroxisome proliferator activated receptor alpha and gamma ligands. Proteomics. 3(4):505-12.

Calver AR, Michalovich D, Testa TT, Robbins MJ, Jaillard C, Hill J, Szekeres PG, Charles KJ, Jourdain S, Holbrook JD, Boyfield I, Patel N, Medhurst AD, Pangalos MN. (2003) Molecular cloning and characterisation of a novel GABAB-related G-protein coupled receptor. Brain Res Mol Brain Res. 20;110(2):305-17.

Patel L, Buckels AC, Kinghorn IJ, Murdock PR, Holbrook JD, Plumpton C, Macphee CH, Smith SA. (2003) Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun. 300(2):472-6.

Holbrook JD, Abramo M., Blaney F., Foord S. (2003) Disregarding evolutionary noise to discover noise to discover functional relationships between genes. Poster presented at HGM2003

Chen L, Zhao Y, Gao F and Garland M (2003) Determination of Enantiomeric Excess using the Ultraviolet-Circular Dichroism and the High-Performance Liquid Chromatography-Circular Dichroism Methods. Applied Spectroscopy 57(7): 797-804

Chen L, Chew W and Garland M (2003) Spectral Pattern Recognition of in situ FT-IR Spectroscopic Reaction Data Using Minimum of Entropy and Spectra Similarity (MESS): Application to the Homogeneous Rhodium Catalyzed Hydroformylation of Isoprene. Applied Spectroscopy,  57(5): 491-498

Chen L and Garland M (2003) Computationally Efficient Curve-Fitting Procedure for Large Two-Dimensional Experimental Infrared Spectroscopic Arrays Using the Pearson VII Model. Applied Spectroscopy 57(3): 331-337

Chen L and Garland M (2003) Band Centers and Track Finding for Large Two-Dimensional Infrared Spectroscopic Arrays.Applied Spectroscopy 57(3):323-330

Tan AH, Ong H, Hong Pan, Ng J and Li QX (2003)Web Intelligence via Personalized Information Management Knowledge and Information Systems 6(5).

Holbrook JD, Danpure CJ. (2002) Molecular basis for the dual mitochondrial and cytosolic localization of alanine:glyoxylate aminotransferase in amphibian liver cells. J Biol Chem. 18;277(3):2336-44.

Chen L, Weng Z, Goh L, Garland M (2002) An Efficient Algorithm for Automatic Phase Correction of NMR Spectra Based on Entropy Minimization Journal of Magnetic Resonance 158: 164-168

Chen L and Garland M (2002) Use of Entropy Minimization for the Preconditioning of Large Spectroscopic Data Arrays: Application to in situ FT-IR Studies from the Unmodified Homogeneous Rhodium Catalyzed Hydroformylation Reaction. Applied Spectroscopy, 56(11) 1422-1428

Holbrook JD, Danpure CJ. (2002) Molecular basis for the dual mitochondrial and cytosolic localization of alanine:glyoxylate aminotransferase in amphibian liver cells. J Biol Chem. 18;277(3):2336-44.

Holbrook JD, Birdsey GM, Yang Z, Bruford MW, Danpure CJ. (2000) Molecular adaptation of alanine:glyoxylate aminotransferase targeting in primates. Mol Biol Evol. 17(3):387-400.

Holbrook JD and Danpure CJ (2000) Molecular evolution of alanine:glyoxylate aminotransferase intracellular targeting. In Biochemistry and Molecular Biology of Vitamin B6 and PQQ-Dependent Proteins (Ana Iriarte, Herbert M. Kagan, Marino Martinez-Carrion eds), p.117-122, Birkhauser

Pan H, Chen L, Dogra S, Ling Teh A, Tan JH, Lim YI, Lim YC, Jin S, Lee YK, Ng PY, Ong ML, Barton S, Chong YS, Meaney MJ, Gluckman PD, Stunkel W, Ding C, Holbrook JD (2012) Measuring the methylome in clinical samples – improved processing of the infiniumHD 450K array.Epigenetics 7(10)

Stünkel W, Pan H, Chew R, Tng E, Tan JH, Joseph R, Cheong C, Chen L, Lee YS,  Chong YS, Mei SS,  Meaney MJ, Kwek K, Sheppard AM, Gluckman PD, Holbrook JD (2012) Transcriptome changes affecting hedgehog and cytokine signalling in the umbilical cord in late pregnancy: potential implications for disease risk PLoS One. 7(7):e39744.

Sandanaraj E and Holbrook JD (2012) Gastric Cancer, oncogenes and targeted therapies Gastric & Breast Cancer international 11(3)

Yeo C, Ng F, Chai C, Tan J, Koh G, Chong YK, Koh L, Foong C, Sandanaraj E, Holbrook JD, Ang BT, Takahashi R, Tang C, Lim KL (2012) Parkin pathway activation mitigates glioma cell proliferation and predicts survival outcome for patients. Cancer Research 72(10):2543-2553

Chen Li
Senior Postdoctoral Fellow

Shaillay Kumar Dogra
Senior Research Bioinformatician

Ong Mei Lyn
Postdoctoral Fellow

Pan Hong
Senior Research Bioinformatician

Johnny Wong
Database Manager

Robin Choo
Statistician

Teh Ai Ling
Research Bioinformatician

Melvir Singh
Web/Software Developer