Mekala Gunaratnam

I joined Prof. Neidle's group in Oct 2003 after completing my PhD in toxicology at Strathclyde University in Glasgow. During the past three years I have been conducting research in the field of Cancer Cell Biology (funded by Antisoma) in relation to novel telomere targeting agents (TTA). I have extensively studied the mechanism of TTAs in various human cancer cell lines representing Breast, Lung, Prostate, Leukaemia, Lymphoma, Melanoma, Gastrointestinal, and Ovarian cancers. I have developed several assays and techniques that facilitated our understanding of how these novel TTAs bring about anti-tumour activities and aided in substantiating our proof of concept. These include cytotoxicity assays, long term growth inhibition studies, Senescence, Apoptosis, measurement of Telomerase activity, Chromosome spreads, Telomere length measurements, Gene and Protein expression studies using Real-Time RT-PCR and Western Blotting, Cell cycle and DNA damage analysis. I am also conducting studies in Combination Therapy involving TTAs and other existing anti-cancer agents with the aim of increasing potency and reducing unwanted side effects associated with most anti-cancer drugs. Currently I am exclusively involved in a study that utilises our TTAs to target oncogenes associated with many Gastrointestinal Stromal Tumours (funded by Heptagon).

A549 un-treated	A549 treated with 2µM TTA (BRACO19) for 1 week
Confocal images showing Human Lung cancer cells, A549, treated with BRACO19 with subsequent induction of apoptosis evident by AnnexinV staining.

Publications

• Martins M, Gunaratnam M, Stuart J, Makwana V, Greciano O, Reszka A, Kelland L and Neidle S. Structure-based design of benzylamino-acridine compounds as G-quadruplex DNA telomere targeting agents. Bioorganic and Medicinal Chemistry Letters, 2007, Jan


• Milroy L, Zinzalla G, Prencipe G, Michel P, Ley S, Gunaratnam M, Beltran M, Neidle S. Chemical variation of natural product-like scaffolds: Design, synthesis and biological activity of fused bicyclic acetal derivatives. Angewandte Chemie, 2007, Feb 23


• Moorhouse AD, Santos AM, Gunaratnam M, Moore M, Neidle S, Moses JE. Stabilization of G-Quadruplex DNA by Highly Specific Ligands via Click Chemistry. Journal of American Chemical Society, 2006, 20;128(50), 15972-3.


• Moore MJ, Schultes CM, Cuesta J, Cuenca F, Gunaratnam M, Tanious FA, Wilson WD, Neidle S. Trisubstituted acridines as G-quadruplex telomere targeting agents I: The role of the 3,6-sidechains in quadruplex binding and telomerase activity. Journal of Medicinal Chemistry, 2006, 49(2), 582-99.


• Sann CL, Baron A, Mann J, van den Berg H, Gunaratnam M, Neidle S. New mustard-linked 2-aryl-bis-benzimidazoles with anti-proliferative activity. , Organic & Biomolecular Chemistry, 2006, 4, 1305-1312.


• Gunaratnam M. and Grant M.H. Damage to F-actin and cell death induced by chromium VI and nickel in primary monolayer cultures of rat hepatocytes. Toxicology In Vitro, 2004, 18(3), 245-53.


• Gunaratnam M. and Grant M.H. The role of glutathione reductase in the cytotoxicity of chromium (VI) in isolated rat hepatocytes. Chemico-Biological Interactions, 2001, vol 134, 191-202.