Sussex Drug Discovery Centre Director
Experimental Therapeutics Centre Deputy Director
GlaxoSmithKline Pharmaceuticals Senior Investigator
Cardiff University, UK Ph.D. in Biochemistry
Cardiff University, UK B.Sc. in Biochemistry
I have been engaged in drug discovery for approximately 25 years, having spent 8 years at GlaxoSmithKline Pharmaceuticals in the UK, 14 years as Head of Biology at A*STAR’s Experimental Therapeutic Centre (ETC) in Singapore and 2 years as Director of the Sussex Drug Discovery Centre, University of Sussex, UK. I have been responsible for all the biology activities associated with preclinical drug discovery including assay development, high throughput screening, biophysics, structural biology, analytics and pre-clinical pharmacology. I firmly believe that to be successful in drug discovery one must utilize cutting edge technologies, explore the full range of drug modalities and attempt to drug the most challenging targets. I am interested in pursuing targets from all therapeutic areas especially oncology and infectious disease.
I have published over 115 peer reviewed articles, been cited over 2500 times (SCI/SCCI) and have an h-index of 26.
During my career I have led a number of drug discovery and biomarker projects. At GSK, I was the program leader for a study to identify novel biomarkers of hepatotoxicity. This program was managed by Discovery Research and Safety Assessment and resulted in the implementation of a number of assays to identify potential toxicants. Also at GSK, I led a number of early stage projects including an MCHR2 receptor antagonist project where we deorphanized a novel GPCR. While working for the Experimental Therapeutics Centre (ETC), A*STAR, Singapore, I led a dengue protease inhibitor project in a collaboration with Duke-NUS. I also led a companion diagnostics program, CDIC (Companion Diagnostics in Cancer) to identify PD and stratification biomarkers for the novel small molecules we generated. This was enabled by the award of a $10M grant. At the Sussex Drug Discovery Centre (SDDC) I led a number of ion channel projects and was a PI on a CRUK funded EBV driven cancer project.
In the Experimental Therapeutics Centre, Singapore, I was Head of Biology. Between 2012 and 2019, we advanced three molecules into clinical development, a seasonal flu vaccine, a MNK inhibitor (currently in Phase I in blast crisis CML patients & Philadelphia positive ALL patients) and a Wnt (Porcupine) inhibitor (currently in Phase Ib in patients with activating Wnt mutations).
Honors and Awards
• Scientific Impact Award - GlaxoSmithKline Pharmaceuticals - Cloning a novel human GPCR
• Exceptional Science Award - GlaxoSmithKline Pharmaceuticals - Identification of novel biomarkers
• Borderless Award - ETC, A*STAR, Singapore - MTI award for first Singapore drug
5 Selected Publications
1. S. Lim, T. Y. Saw, M. Zhang, M. R. Janes, K. Nacro, J. Hill, A. Q. Lim, C. T. Chang, D. A. Fruman, D. A. Rizzieri, S. Y. Tan, H. Fan, C. T. Chuah, S. T. Ong, Targeting of the MNK-eIF4E axis in blast crisis chronic myeloid leukemia inhibits leukemia stem cell function. Proceedings of the National Academy of Sciences of the United States of America 110, E2298-2307 (2013).
2. X. Koh-Stenta, J. Joy, A. Poulsen, R. Li, Y. Tan, Y. Shim, J.-H. Min, L. Wu, A. Ngo, J. Peng, Wei G. Seetoh, J. Cao, John Liang K. Wee, Perlyn Z. Kwek, A. Hung, U. Lakshmanan, H. Flotow, E. Guccione, J. Hill, Characterization of the histone methyltransferase PRDM9 using biochemical, biophysical and chemical biology techniques. Biochemical Journal 461, 323-334 (2014).
3. B. Madan, Z. Ke, N. Harmston, S. Y. Ho, A. O. Frois, J. Alam, D. A. Jeyaraj, V. Pendharkar, K. Ghosh, I. H. Virshup, V. Manoharan, E. H. Ong, K. Sangthongpitag, J. Hill, E. Petretto, T. H. Keller, M. A. Lee, A. Matter, D. M. Virshup, Wnt addiction of genetically defined cancers reversed by PORCN inhibition. Oncogene 35, 2197-2207 (2016).
4. X. Koh-Stenta, A. Poulsen, R. Li, J. L. Wee, P. Z. Kwek, S. Y. Chew, J. Peng, L. Wu, E. Guccione, J. Joy, J. Hill, Discovery and characterisation of the automethylation properties of PRDM9. The Biochemical journal 474, 971-982 (2017).
5. B. H. Liu, C. Jobichen, C. S. B. Chia, T. H. M. Chan, J. P. Tang, T. X. Y. Chung, J. Li, A. Poulsen, A. W. Hung, X. Koh-Stenta, Y. S. Tan, C. S. Verma, H. K. Tan, C. S. Wu, F. Li, J. Hill, J. Joy, H. Yang, L. Chai, J. Sivaraman, D. G. Tenen, Targeting cancer addiction for SALL4 by shifting its transcriptome with a pharmacologic peptide. Proceedings of the National Academy of Sciences of the United States of America 115, E7119-E7128 (2018).