Staff profile

Kalesh Karunakaran completed his MSc in Chemistry at the Indian Institute of Technology (IIT), Madras. He then pursued his PhD (received 2010) in Chemical Biology with Professor Yao Shao Qin at the National University of Singapore (NUS). His thesis focussed on the development of chemical tools, mainly using the activity-based protein profiling (ABPP) approach and rapid assembly of chemical compound libraries using the modular “click chemistry” approach, for the studies of protein kinases and protein phosphatases. Following his PhD, he joined in the R&D division of Albany Molecular Research Inc. (AMRI) Singapore as a senior research scientist and worked on the Medicinal chemistry and Structure-Activity-Relationship (SAR) studies of a number of inhibitor lead compounds. After a brief stint in the pharma industry, in 2012 he switched back to academic research with a Marie Curie individual fellowship from the European Research Agency and joined the research group of Professor Ed Tate in the Department of Chemistry of Imperial College London. Here he focussed on the development of chemical probes for the profiling of post-translational modifications arginine methylation and lysine succinylation and development of a competition-based ‘spike-in’ SILAC-quantitative chemical proteomics method for the target profiling of pharmacologically active natural products. In 2015, he joined the proteomics & mass-spectrometry group of Dr Peter DiMaggio in the Department of Chemical Engineering of Imperial College to work on a GSK-funded Engineered Medicines Laboratory project. Here he developed novel MS-chemical proteomics technologies for the study of intracellular ADP-ribosylation in cancer cells. In January 2019 he joined the Department of Chemistry of Durham University as an Assistant Professor (Research – GCRF NTD Research Fellow). His research interest is in developing and applying chemical biology and chemical proteomics methods for identifying and validating new drug targets for Leishmaniasis and Chagas disease. 

• Chemical Biology
• Chemical Proteomics

Journal Article

• Mina, J. G., Parthasarathy, A., Porta, E. O., Denny, P. W., & Kalesh, K. (2024). BONCAT-iTRAQ Labelling Reveals Molecular Markers of Adaptive Responses in Toxoplasma gondii to Pyrimethamine Treatment. Pathogens, 13(10), Article 879. https://doi.org/10.3390/pathogens13100879
• Porta, E. O., Gao, L., Denny, P. W., Steel, P. G., & Kalesh, K. (2023). Inhibition of HSP90 distinctively modulates the global phosphoproteome of Leishmania mexicana developmental stages. Microbiology Spectrum, 11(6), Article e02960-23. https://doi.org/10.1128/spectrum.02960-23
• Karunakaran, K., Sundriyal, S., Perera, H., Cobb, S. L., & Denny, P. W. (2021). Quantitative Proteomics Reveals that Hsp90 Inhibition Dynamically Regulates Global Protein Synthesis in Leishmania mexicana. mSystems, 6(3), Article e00089-21. https://doi.org/10.1128/msystems.00089-21
• Mantilla, B. S., Karunakaran, K., Brown, N. W., Fiedler, D., & Docampo, R. (2021). Affinity‐based proteomics reveals novel targets of inositol pyrophosphate (5‐IP7)‐dependent phosphorylation and binding in Trypanosoma cruzi replicative stages. Molecular Microbiology, 115(5), 986-1004. https://doi.org/10.1111/mmi.14672
• Mantravadi, P. K., Parthasarathy, A., & Karunakaran, K. (2021). Antileishmanial Drug Development: A Review of Modern Molecular Chemical Tools and Research Strategies. Current Medicinal Chemistry, 28(31), 6337 - 6357. https://doi.org/10.2174/0929867328666201125121018
• Parthasarathy, A., Mantravadi, P. K., & Karunakaran, K. (2020). Detectives and helpers: Natural products as resources for chemical probes and compound libraries. Pharmacology and Therapeutics, 216, Article 107688. https://doi.org/10.1016/j.pharmthera.2020.107688
• Parthasarathy, A., & Karunakaran, K. (2020). Defeating the trypanosomatid trio: proteomics of the protozoan parasites causing neglected tropical diseases. RSC Medicinal Chemistry, 11(6), 625-645. https://doi.org/10.1039/d0md00122h
• Denny, P. W., & Karunakaran, K. (2020). How can proteomics overhaul our understanding of Leishmania biology?. Expert Review of Proteomics, 17(11-12), 789-792. https://doi.org/10.1080/14789450.2020.1885375
• Karunakaran, K., & Denny, P. W. (2019). A BONCAT-iTRAQ method enables temporally resolved quantitative profiling of newly synthesised proteins in Leishmania mexicana parasites during starvation. PLoS Neglected Tropical Diseases, 13(12), Article e0007651. https://doi.org/10.1371/journal.pntd.0007651
• Karunakaran, K., Lukauskas, S., Borg, A. J., Snijders, A. P., Ayyappan, V., Leung, A. K., Haskard, D. O., & DiMaggio, P. A. (2019). An Integrated Chemical Proteomics Approach for Quantitative Profiling of Intracellular ADP-Ribosylation. Scientific Reports, 9, Article 6655. https://doi.org/10.1038/s41598-019-43154-1
• Mantravadi, P., Karunakaran, K., Dobson, R., Hudson, A., & Parthasarathy, A. (2019). The Quest for Novel Antimicrobial Compounds: Emerging Trends in Research, Development, and Technologies. Antibiotics, 8(1), Article 8. https://doi.org/10.3390/antibiotics8010008
• Clulow, J. A., Storck, E. M., Lanyon-Hogg, T., Kalesh, K. A., Jones, L. H., & Tate, E. W. (2017). Competition-based, quantitative chemical proteomics in breast cancer cells identifies new target profiles for sulforaphane. Chemical Communications, 53(37), 5182-5185. https://doi.org/10.1039/c6cc08797c
• Ong, Y. S., Gao, L., Kalesh, K. A., Yu, Z., Wang, J., Liu, C., Li, Y., Sun, H., & Lee, S. S. (2017). Recent Advances in Synthesis and Identification of Cyclic Peptides for Bioapplications. Current Topics in Medicinal Chemistry, 17(20), https://doi.org/10.2174/1568026617666170224121658
• Wong, Y. K., Xu, C., Kalesh, K. A., He, Y., Lin, Q., Wong, W. F., Shen, H.-M., & Wang, J. (2017). Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action. Medicinal Research Reviews, 37(6), https://doi.org/10.1002/med.21446
• Parthasarathy, A., Anandamma, S. K., & Kalesh, K. A. (2017). The Medicinal Chemistry of Therapeutic Peptides: Recent Developments in Synthesis and Design Optimizations. Current Medicinal Chemistry, 24, https://doi.org/10.2174/0929867324666171012103559
• Cioffi, C. L., Liu, S., Wolf, M. A., Guzzo, P. R., Sadalapure, K., Parthasarathy, V., Loong, D. T., Maeng, J.-H., Carulli, E., Fang, X., Karunakaran, K., Matta, L., Choo, S. H., Panduga, S., Buckle, R. N., Davis, R. N., Sakwa, S. A., Gupta, P., Sargent, B. J., Moore, N. A., …Mhyre, A. J. (2016). Synthesis and Biological Evaluation of N-((1-(4-(Sulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide Inhibitors of Glycine Transporter-1. Journal of Medicinal Chemistry, 59(18), 8473-8494. https://doi.org/10.1021/acs.jmedchem.6b00914
• Wang, J., Gao, L., Lee, Y. M., Kalesh, K. A., Ong, Y. S., Lim, J., Jee, J.-E., Sun, H., Lee, S. S., Hua, Z.-C., & Lin, Q. (2016). Target identification of natural and traditional medicines with quantitative chemical proteomics approaches. Pharmacology and Therapeutics, 162, https://doi.org/10.1016/j.pharmthera.2016.01.010
• Wang, J., Zhang, C., Liu, L., Kalesh, K. A., Qiu, L., Ding, S., Fu, M., Gao, L.-Q., & Jiang, P. (2016). A capillary electrophoresis method to explore the self-assembly of a novel polypeptide ligand with quantum dots. ELECTROPHORESIS, 37(15-16), https://doi.org/10.1002/elps.201600164
• Kalesh, K. A., Clulow, J. A., & Tate, E. W. (2015). Target profiling of zerumbone using a novel cell-permeable clickable probe and quantitative chemical proteomics. Chemical Communications, 51(25), 5497-5500. https://doi.org/10.1039/c4cc09527h
• Tate, E. W., Kalesh, K. A., Lanyon-Hogg, T., Storck, E. M., & Thinon, E. (2015). Global profiling of protein lipidation using chemical proteomic technologies. Current Opinion in Chemical Biology, 24, https://doi.org/10.1016/j.cbpa.2014.10.016
• Kalesh, K. A., & Tate, E. W. (2014). A succinyl lysine-based photo-cross-linking peptide probe for Sirtuin 5. Organic and Biomolecular Chemistry, 12(25), https://doi.org/10.1039/c4ob00773e
• Prasannan, R., Kalesh, K. A., Shanmugam, M. K., Nachiyappan, A., Ramachandran, L., Nguyen, A. H., Kumar, A. P., Lakshmanan, M., Ahn, K. S., & Sethi, G. (2012). Key cell signaling pathways modulated by zerumbone: Role in the prevention and treatment of cancer. Biochemical Pharmacology, 84(10), https://doi.org/10.1016/j.bcp.2012.07.015
• Sasikala, K. A., Kalesh, K. A., Anabha, E. R., Pillai, P. M., Asokan, C. V., & Devaky, K. S. (2011). Synthesis of 2,3,5-trisubstituted furans from α-formylaroylketene dithioacetals. Tetrahedron Letters, 52(14), https://doi.org/10.1016/j.tetlet.2011.01.128
• Kalesh, K. A., Tan, L. P., Lu, K., Gao, L., Wang, J., & Yao, S. Q. (2010). Peptide-based activity-based probes (ABPs) for target-specific profiling of proteintyrosine phosphatases (PTPs). Chemical Communications, 46(4), https://doi.org/10.1039/b919744c
• Kalesh, K. A., Sim, D. S. B., Wang, J., Liu, K., Lin, Q., & Yao, S. Q. (2010). Small molecule probes that target Ablkinase. Chemical Communications, 46(7), https://doi.org/10.1039/b919888a
• Kalesh, K. A., Shi, H., Ge, J., & Yao, S. Q. (2010). The use of click chemistry in the emerging field of catalomics. Organic and Biomolecular Chemistry, 8(8), https://doi.org/10.1039/b923331h
• Tan, L. P., Wu, H., Yang, P.-Y., Kalesh, K. A., Zhang, X., Hu, M., Srinivasan, R., & Yao, S. Q. (2009). High-Throughput Discovery ofMycobacterium tuberculosisProtein Tyrosine Phosphatase B (MptpB) Inhibitors Using Click Chemistry. Organic Letters, 11(22), https://doi.org/10.1021/ol9023419
• Srinivasan, R., Tan, L. P., Wu, H., Yang, P.-Y., Kalesh, K. A., & Yao, S. Q. (2009). High-throughput synthesis of azide libraries suitable for direct “click” chemistry and in situ screening. Organic and Biomolecular Chemistry, 7(9), https://doi.org/10.1039/b902338k
• Kalesh, K. A., Liu, K., & Yao, S. Q. (2009). Rapid synthesis of Abelson tyrosine kinase inhibitors using click chemistry. Organic and Biomolecular Chemistry, 7(24), https://doi.org/10.1039/b913333j
• Liu, K., Kalesh, K. A., Bing Ong, L., & Yao, S. Q. (2008). An Improved Mechanism-Based Cross-Linker for Multiplexed Kinase Detection and Inhibition in a Complex Proteome. ChemBioChem, 9(12), https://doi.org/10.1002/cbic.200800212
• Kalesh, K., Yang, P.-Y., Srinivasan, R., & Yao, S. (2007). Click Chemistry as a High-Throughput Amenable Platform in Catalomics. QSAR & combinatorial science (Internet), 26(11-12), https://doi.org/10.1002/qsar.200740064
• Srinivasan, R., Li, J., Ng, S. L., Kalesh, K. A., & Yao, S. Q. (2007). Methods of using click chemistry in the discovery of enzyme inhibitors. Nature Protocols, 2(11), https://doi.org/10.1038/nprot.2007.323
• Nair, A. S., Subramaniam, C., Rosemary, M. J., Tom, R. T., Kumar, V. R. R., Singh, D. M. D. J., Cyriac, J., Jain, P., Kalesh, K. A., Bhattacharya, S., & Pradeep, T. (2005). Nanoparticles-chemistry, new synthetic approaches, gas phase clustering and novel applications. Pramana - Journal of Physics, 65(4), https://doi.org/10.1007/bf03010451