Biologic Systems Group

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The Biologic Systems Group focuses on modulation and target validation of tumour suppressor pathways by small molecules, functional determination of genetic variants of unknown significance (VUS) among patient derived cellular samples as well the functional evolution of the p53, HDM2 and BRCA family members. These studies are accomplished through a number of local and international collaborations as well as in-house experimental techniques, including protein interference, high-throughput screens of small molecules; structure activity relationship (SAR) investigations; resistance studies using whole genome knockouts by CRISPR; proteome and binding partner investigations by mass spectrometry; tissue culture phenotypic screens; cell signalling pathway elucidation; molecular biology; cloning; qPCR; FACS and assay designs.

Current members
Cindy Coffill
David Koschut
Mani Periyasamy
Aidana Shagirova
Yuezhen Xue
Kol Jia Yong

Publications

Xue Y, San Luis B, Lane DP*. Intratumour heterogeneity of p53 expression; causes and consequences. J Pathol. 2019 Nov;249(3):274-285 doi: 10.1002/path.5328.

Xue Y*, Barker N, Hoon S, He P, Thakur T, Abdeen SR, Maruthappan P, Ghadessy FJ, Lane DP. Bortezomib Stabilizes and Activates p53 in Proliferative Compartments of both Normal and Tumor Tissues in Vivo. Cancer Res. 2019, 79(14): 3595-3607. (Cover Figure in the Jul 15 issue)

Yuen TY*, Brown CJ, Xue Y, Tan YS, Ferrer Gago FJ, Lee XE, Neo JY, Yong , Thean D, Kaan HYK, Partridge AW, Verma CS, Lane DP, Johannes CW. Stereoisomerism of All-Hydrocarbon Stapled Peptide Inhibitors of the p53-Mdm2 Interaction: an Assessment of Synthetic Strategies and Activity Profiles. Chem Sci. 2019, 10(26):6457-6466.

Hwang LA, Phang BH, Liew OW, Iqbal J, Koh XH, Koh XY, Othman R, Xue Y, Richards AM, Lane DP*, Sabapathy K*. Monoclonal Antibodies against Specific p53 Hotspot Mutants as Potential Tools for Precision Medicine. Cell Rep. 2018, 22(1):299-312.

Ding CYG, Ong JFM, Goh HC, Coffill CR, and Tan LT. (2018) Benderamide A, a Cyclic Depsipeptide from a Singapore Collection of Marine Cyanobacterium Lyngbya. Marine Drugs.16: pii: E409.

Tan BX, Liew HP, Chua JS, Ghadessy FJ, Tan YS, Lane DP, and Coffill CR. (2017) Anatomy of Mdm2 and Mdm4 in evolution. J Mol Cell Biol. 9: 3-15

Xue Y, A Raharja, W Sim, E S M Wong, S A B Rahmat and D P Lane*. The hot-spot p53R172H mutant promotes formation of giant spermatogonia triggered by DNA damage. Oncogene. 2017, 36(14):2002-2013.

Siau JW, Coffill CR, Zhang WV, Tan YS, Hundt J, Lane D, Verma C, and Ghadessy F. (2016) Functional characterization of p53 pathway components in the ancient metazoan Trichoplax adhaerens. Sci Rep.6: 33972.

Coffill CR, Lee AP, Siau JW, Chee SM, Joseph TL, Tan YS, Madhumalar A, Tay BH, Brenner S, Verma CS, Ghadessy FJ, Venkatesh B, and Lane DP. (2016) The p53-Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans. Genes Dev. 30: 281-92.

Meuris F, Carthagena L, Jaracz-Ros A, Gaudin F, Cutolo P, Deback C, Xue Y, Thierry F, Doorbar J, Bachelerie F* . The CXCL12/CXCR4 Signaling Pathway: A New Susceptibility Factor in Human Papillomavirus Pathogenesis. PLoS Pathog. 2016, 12(12):e1006039. doi: 10.1371/journal.ppat.1006039.

Penny HL, Sieow JL, Adriani G, Yeap WH, Ee PSC, San Luis B, Lee B, Lee T, Mak SY, Ho YS, Lam KP, Ong CK, Huang RYJ, Ginhoux F, Rotzschke O, Kamm RD, Wong SC*. Warburg metabolism in tumor-conditioned macrophages promote metastasis in human pancreatic ductal adenocarcinoma. Oncoimmunology. 2016, 5(8):e1191731.

Eng HY, Wang CI, Xue Y, Lee CY, Binte Zulkifli S, Chiam PC, Ghadessy FJ, Lane DP*. Enhanced antigen detection in immunohistochemical staining using a 'digitized' chimeric antibody. Protein Eng Des Sel. 2016, 29(1):11-21.

Muller PA, Trinidad AG, Timpson P, Morton JP, Zanivan S, van den Berghe PV, Nixon C, Karim SA, Caswell PT, Noll JE, Coffill CR, Lane DP, Sansom OJ, Neilsen PM, Norman JC, Vousden KH. (2013). Mutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion. Oncogene.32: 1252-65.

Coffill CR, 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 Rep.

Coffill CR, Lane DP. (2011). The role of mutant p53 in human cancer. J Pathol. 223: 116-26.