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Personal profile

Academic Biography

Dr Kalesh Karunakaran is a Lecturer in Chemistry at Teesside University. His research uses synthetic chemical tools, proteomic mass spectrometry and bioinformatics to understand living systems. After completing MSc in Chemistry at the Indian Institute of Technology Madras, Kalesh undertook his PhD in Chemical Biology at the National University of Singapore under the guidance of Prof. Yao Shao Qin. After receiving PhD in 2010, he joined as senior research scientist in the drug discovery unit of the pharmaceutical company Albany Molecular Research Inc. (now Curia) in the company’s Singapore site. At AMRI Singapore, he worked on two major drug discovery projects (Glycine Transporter-1 project & 5-HT6 project), contributed to the structure-activity-relationship studies of a number of inhibitor lead compounds and gained experience in the integrated drug discovery process in the pharmaceutical industry environment. In 2012 Kalesh received the Marie Curie Individual Fellowship from the European Research Agency (total grant amount € 209,033.40) and started his academic postdoctoral research with Prof. Ed Tate at Imperial College London to study posttranslational modifications of proteins using novel chemical probes and quantitative proteomic mass spectrometry. From 2014 to 2015, with Prof. Ed Tate, Kalesh worked on a Medical Research Council (MRC) UK Confidence-in-Concept grant to evaluate the therapeutic scope of orally active inhibitors of human N-myristoyltransferase enzyme in cancer. During this period, he collaborated extensively with leading cancer researchers at the Institute of Cancer Research (ICR) Sutton, UK. In 2015, Kalesh joined the proteomics and mass spectrometry group of Dr Peter DiMaggio at the Department of Chemical Engineering of Imperial to work on a GSK-funded project. Here he collaborated with researchers at the Department of Medicine of Imperial College, The Francis-Crick Institute London and GSK Stevenage to develop novel mass-spectrometry-based quantitative chemical proteomic methodologies for the characterisation of ADP-ribosylation in cancer cells. Following postdoctoral positions at Imperial (2012-2018), he was an Assistant Professor (Research) at Durham University (2019-2021), where, with the support of the MRC-Global Challenges Research Fund (£50,000), he independently established and led a research programme that resulted in several discoveries around the functional proteome of the Leishmania spp. parasites, the causative agents of the complex neglected tropical disease leishmaniasis.    

Kalesh has published over 30 articles in leading scientific journals including Nature Protocols, Microbiology Spectrum, mSystems, Journal of Medicinal Chemistry, Chemical Communications, Organic Letters, Scientific Reports, etc. He also serves as a reviewer of numerous scientific journals. 

Kaleshs's publications can be found on his Google Scholar page https://scholar.google.co.uk/citations?user=3RUsC3sAAAAJ&hl=en.

Summary of Research Interests

Kalesh’s research uses synthetic organic chemistry to generate functional tools that facilitate understanding of living systems. Specifically, in the area of chemical proteomics, his research develops and apply small molecule chemical probes to understand the functions of proteins, the workhorses of the living cell. Many proteins undergo posttranslational modifications (PTMs) and the PTMs alter the properties of the protein and play a crucial role in the biological function of the protein. Kalesh is interested in understanding how dysregulation of certain PTMs such as phosphorylation and ADP-ribosylation modulate cell signalling pathways and contribute to the development of diseases such as cancer. Another major area of interest is to understand the protein interactions and unknown functions of heat shock proteins. His research is multidisciplinary and incorporates a range of methodology including small molecule and peptide syntheses, biochemical techniques, cell- and molecular biology techniques, quantitative proteomic mass spectrometry, transcriptomics, computational methods, and bioinformatics. 

Current projects include:

  • Developing new chemical tools to unravel the functions of heat shock proteins in cancer.
  • Development of inhibitors of heat shock proteins.
  • Development of new protein labelling and detection strategies.
  • Developing new chemical tools for probing the Nicotinamide Adenine Dinucleotide (NAD+)-dependent enzymes and NAD+ redox pathways in live cells.
  • Characterisation and understanding of protein-protein interactions using chemical tools and proteomics mass spectrometry.
  • Profiling and functional characterisation of protein-nucleic acid interactions.

Publications

  • K. Kalesh*, W. Wei, B. S. Mantilla, T. I. Roumeliotis, J. Choudhary and P. W. Denny, “Transcriptome-wide identification of coding and noncoding RNA-binding proteins defines the comprehensive RNA-interactome of Leishmania mexicana”. Microbiol. Spectr., 2022, 10(1). *Corresponding author. DOI: 10.1128/spectrum.02422-21
  • K. Kalesh*, S. Sundriyal, H. Perera, S. L. Cobb and P. W. Denny, “Quantitative proteomics reveals that Hsp90 inhibition dynamically regulates global protein synthesis in Leishmania mexicana”. mSystems, 2021, 6, e00089-21. *Corresponding author. DOI: 10.1128/mSystems.00089-21
  • P. W. Denny* and K. Kalesh*, “How can proteomics overhaul our understanding of Leishmania biology”. Expert Rev. Proteomic., 2021, 17(11-12), 789-792. *Corresponding author. DOI: 10.1080/14789450.2020.1885375
  • P. K. Mantravadi, A. Parthasarathy and K. Kalesh*, “Antileishmanial Drug Development: A Review of Modern Molecular Chemical Tools and Research Strategies”. Curr. Med. Chem., 2021, 28(31), 6337-6357. *Corresponding author. DOI: 10.2174/0929867328666201125121018
  • B. S. Mantilla, K. Kalesh, N. W. Brown Jr, D. Fiedler and R. Docampo, “Affinity-based proteomics reveals novel targets of inositol pyrophosphate (5-IP7)-dependent phosphorylation and binding in Trypanosoma cruzi replicative stages”. Mol. Microbiol., 2021, 115(5), 986-1004. DOI: 10.1111/mmi.14672
  • A. Parthasarathy, P. K. Mantravadi and K. Kalesh*, “Detectives and helpers: Natural products as resources for chemical probes and compound libraries”. Pharmacol. Ther., 2020, 216, 107688. *Corresponding author. DOI: 10.1016/j.pharmthera.2020.107688
  • A. Parthasarathy and K. Kalesh*, “Defeating the trypanosomatid trio: proteomics of the protozoan parasites causing neglected tropical diseases”. RSC Med. Chem., 2020, 11, 625. *Corresponding author. DOI: 10.1039/d0md00122h
  • K. Kalesh* and P. W. Denny, “A BONCAT-iTRAQ method enables temporally resolved quantitative profiling of newly synthesised proteins in Leishmania mexicana parasites during starvation” PLoS Negl. Trop. Dis., 2019, 13(12). e0007651. *Corresponding author. DOI: 10.1371/journal.pntd.0007651
  • K. Kalesh, S. Lukauskas, A. J. Borg, A. P. Snijders, V. Ayyappan, A. K. L. Leung, D. O. Haskard and P. A. DiMaggio, “An Integrated Chemical Proteomics Approach for Quantitative Profiling of Intracellular ADP-Ribosylation”. Sci. Rep., 2019, 9, 6655. DOI: 10.1038/s41598-019-43154-1
  • A. Parthasarathy, S. K. Anandamma and K. A. Kalesh*, “The medicinal chemistry of therapeutic peptides: Recent developments in synthesis and design optimizations”, Curr. Med. Chem., 2019, 26, 2330-2355. *Corresponding author. DOI: 10.2174/0929867324666171012103559
  • M. Pavan, K. Kalesh, D. Renwick, A. Hudson and A. Parthasarathy, “The Quest for Novel Antimicrobial Compounds: Emerging Trends in Research, Development, and Technologies”, Antibiotics, 2019, 8, 8. DOI: 10.3390/antibiotics8010008
  • J. A. Clulow, E. M. Storck, T. Lanyon-Hogg, K. A. Kalesh, L. H. Jones and E. W. Tate, “Competition-based quantitative chemical proteomics in breast cancer cells identifies new target profiles for sulforaphane”, Chem. Commun., 2017, 53, 5182-5185. DOI: 10.1039/c6cc08797c
  • Y. K. Wong, C. Xu, K. A. Kalesh, Y. He, Q. Lin, W. S. F. Wong, H-M Shen and J. Wang, “Artemisinin as an anticancer drug: Recent advances in target profiling and mechanism of action”, Med. Res. Rev., 2017, 37, 1492-1517. DOI: 10.1002/med.21446
  • K. A. Kalesh, J. A. Clulow and E. W. Tate, “Target profiling of zerumbone using a novel cell-permeable probe and quantitative chemical proteomics”, Chem. Commun., 2015, 51, 5497-5500. DOI: 10.1039/c4cc09527h
  • E. W. Tate, K. A. Kalesh, T. Lanyon-Hogg, E. M. Storck and E. Thinon, “Global profiling of protein lipidation using chemical proteomic technologies”, Curr. Opin. Chem. Biol., 2015, 24, 48-57. DOI: 10.1016/j.cbpa.2014.10.016
  • K. A. Kalesh and E. W. Tate, “A succinyl lysine-based photo-cross-linking peptide probe for sirtuin 5”, Org. Biomol. Chem., 2014, 12, 4310-4313. DOI: 10.1039/c4ob00773e
  • Y. S. Ong, L. Gao, K. A. Kalesh, Z. Yu, J. Wang, C. Liu, Y. Li, H. Sun and S. S. Lee, “Recent Advances in Synthesis and Identification of Cyclic Peptides for Bioapplications”, Curr. Top. Med. Chem., 2017, 17, 2302-2318. DOI: 10.2174/1568026617666170224121658
  • J. Wang, L. Gao, Y. M. Lee, K. A. Kalesh, Y. S. Ong, J. Lim, J-E. Jee, H. Sun, S. S. Lee, Z-C. Hua and Q. Lin, “Target identification of natural and traditional medicines with quantitative chemical proteomics approaches”, Pharmacol. Ther., 2016, 162, 10-22. DOI: 10.1016/j.pharmthera.2016.01.010
  • C. Cioffi, S. Liu, M. Wolf, P. Guzzo, K. Sadalapure, P. Visweswaran; D. Loong, J-H. Maeng, E. Carulli, X. Fang, K. A. Kalesh, L. Matta, S. H. Choo, S. Panduga, R. Buckle, R. Davis, S. Sakwa, P. Gupta, B. Sargent, N. Moore, M. Luche, G. Carr, Y. Khmelnitsky, J. Ismail, M. Chung, M. Bai, W. Leong, N. Sachdev, S. Swaminathan and A. Mhyre, “Synthesis and Biological Evaluation of N-((1-(4-(Sulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide Inhibitors of Glycine Transporter-1”, J. Med. Chem., 2016, 59, 8473-8494. DOI: 10.1021/acs.jmedchem.6b00914
  • R. Prasannan, K. A. Kalesh, M. K. Shanmugam, A. Nachiyappan, L. Ramachandran, A. H. Nguyen, A. P. Kumar, M. Lakshmanan, K. S. Ahn and G. Sethi, “Key cell signaling pathways modulated by zerumbone: role in the prevention and treatment of cancer”, Biochem. Pharmacol., 2012, 84, 1268-1276. DOI: 10.1016/j.bcp.2012.07.015
  • J. Wang, C. Zhang, L. Liu, K. A. Kalesh, L. Qiu, S. Ding, M. Fu, L. Gao and P. Jiang, “A capillary electrophoresis method to explore the self-assembly of a novel polypeptide ligand with quantum dots”, Electrophoresis, 2016, 37, 2156-2162. DOI: 10.1002/elps.201600164
  • A. Sasikala, K. A. Kalesh, E. R. Anabha, P. M. Pillai, C. V. Asokan and K. S. Devaky, “Synthesis of 2, 3, 5-trisubstituted furans from α-formylaroylketenedithioacetals”, Tetrahedron Lett., 2011, 52, 1667-1669. https://doi.org/10.1016/j.tetlet.2011.01.128
  • K. A. Kalesh, S. B. D Sim, J. Wang, K. Liu, Q. Lin and S. Q. Yao, “Small molecule probes that target Abl kinase”, Chem. Commun., 2010, 46, 1118-1120. DOI: 10.1039/b919888a
  • K. A. Kalesh, L. P. Tan, K. Liu, L. Gao, J. Wang and S. Q. Yao, “Peptide-based activity-based probes (ABPs) for target-specific profiling of protein tyrosine phosphatases (PTPs)”, Chem. Commun., 2010, 46, 589-591. DOI: 10.1039/b919744c
  • K. A. Kalesh, K. Liu and S. Q. Yao, “Rapid synthesis of abelson tyrosine kinase inhibitors using click chemistry”, Org. Biomol. Chem., 2009, 7, 5129-5136. DOI: 10.1039/b913333j
  • K. A. Kalesh, H. Shi, J. Ge and S. Q. Yao, “The use of click chemistry in the emerging field of catalomics”, Org. Biomol. Chem., 2010, 8, 1749-1762. DOI: 10.1039/b923331h
  • A. Kalesh, P. -Y. Yang, R. Srinivasan and S. Q. Yao, “Click chemistry as a high-throughput amenable platform in catalomics”. QSAR Comb. Sci., 2007, 26, 1135-1144. DOI: 10.1002/qsar.200740064
  • K. Liu, K. A. Kalesh, L. B.Ong and S. Q. Yao, “An improved mechanism-based cross-linker for multiplexed kinase detection and inhibition in a complex proteome”. ChemBioChem, 2008, 9, 1883-1888. DOI: 10.1002/cbic.200800212
  • L. P. Tan, H. Wu, P. –Y. Yang, K. A. Kalesh, X.Zhang, M. Hu, R. Srinivasan and S. Q. Yao, “High-throughput discovery of mycobacterium tuberculosis protein tyrosine phosphatase (MptpB) inhibitors using click chemistry”, Org. Lett., 2009, 11, 5102-5105. DOI: 10.1021/ol9023419
  • R. Srinivasan, J. Li, S. L. Ng, K. A. Kalesh and S. Q. Yao, “Methods of using click chemistry in the discovery of enzyme inhibitors”. Nat. Protoc., 2007, 2, 2655-2664. DOI: 10.1038/nprot.2007.323
  • R. Srinivasan, L. P. Tan, H. Wu, P. –Y. Yang, K. A. Kalesh and S. Q. Yao, “High-throughput synthesis of azide libraries suitable for direct click chemistry and in situ screening”, Org. Biomol. Chem., 2009, 7, 1821-1828. DOI: 10.1039/b902338k

Learning and Teaching Interests and Activities

Dr Kalesh is currently teaching the following modules:

  • Introduction to Organic Chemistry (Year 1), Module leader
  • Organic Chemistry (Year 2), Module contributor
  • Chemical Information Processing (Year 2), Module contributor
  • Life Science Research Project (MSc), Module contributor

PhD and Research Opportunities

Currently no funded positions are available. However, informal enquiries from potential PhD and postdoctoral candidates who are prepared to apply for external research funding are welcome to contact me. Full assistance will be given in preparing a competitive research proposal for outstanding researchers.

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