Doctoral scholar,
Department of Biosciences and Bioengineering,
Indian Institute of Technology Guwahati,
Guwahati, Assam-781039, INDIA
I am Thirukumaran K, pursuing PhD under the supervision of Prof. Siddhartha Sankar Ghosh in the Department of Biosciences and Bioengineering, Indian Institute of Technology, Guwahati, India. Our research group is specialising in EMT dynamics, Bio-microfluidics and metastasis, Cancer therapeutics, and Nanotheranostics. Interdisciplinary research is being routinely persuaded in our group. The function of various signalling molecules and therapeutic modules in EMT and metastasis are being explored, and molecular signalling changes in detail are delineated.
This proposal has focused on the altered metabolism and EMT (epithelial to mesenchymal transition) signaling network of breast cancer. Altered metabolism is one of the hallmarks of cancer, in which cancer cells rewire their metabolic pathways to fulfil the massive energy requirement for rapid proliferation. Aerobic glycolysis is the well-established altered metabolism of glucose in cancer cells (i.e., Warburg effect). The number of ATP produced through oxidative phosphorylation is 15 to 20 times higher than the aerobic glycolysis. To balance the reduced ATP production through aerobic glycolysis, cancer cells uptake more glucose and increase the rate of aerobic glycolysis. Recent research evidence suggests that enzymes involved in the aerobic glycolysis can drive EMT, thereby potentiating metastasis. Mutually EMT also triggers the metabolic rewiring in cancer cells. During EMT, the epithelial phenotypic cancer cells acquire mesenchymal properties and detach from extracellular matrixes. This transition causes detachment triggered ATP deficiency as a result of reduced glucose uptake. After the mesenchymal transition, cancer cells undergo different phases of metastasis such as invasion, intravasation, circulation, extravasation and colonisation. In all these phases, the availability of nutrients is uncertain and the degree of stress brought by the environment is also higher, so the cancer cells rewire their metabolic pathways accordingly to tackle the stress. Under this metabolic stress, essential ATPs and biomass are generated from fatty acid oxidation and autophagy. Therefore, perturbating the interconnected network of EMT signaling and altered metabolism by targeting multiple proteins in the network can be evaluated as a potential therapeutic regime for breast cancer.
Construction of metabolic and EMT signaling network for breast cancer
Target selection and virtual screening for potent drug
Cell signaling studies to check the perturbation of network
Synthesis and characterisation of nanomaterials for targeted drug delivery
Investigation of targeted drug delivery by nanomaterials in breast cancer cells
Publication: Kandasamy, Thirukumaran, Plaboni Sen, and Siddhartha Sankar Ghosh. "Multi‐targeted Drug Repurposing Approach for Breast Cancer via Integrated Functional Network Analysis." Molecular Informatics (2022): 2100300.
May 2022 review - Recommendation with Commendation
1. Sen, Plaboni, Thirukumaran Kandasamy, and Siddhartha Sankar Ghosh. "Multi-targeting TACE/ADAM17 and gamma-secretase of notch signalling pathway in TNBC via drug repurposing approach using Lomitapide." Cellular Signalling 102 (2023): 110529.
2. Naskar, Debdut, Arindam Sain, Dipsikha Khamrai, and Thirukumaran Kandasamy. "Apigenin exerts anti-cancer effects in colon cancer possibly by regulating Heat shock protein 90 alpha family class A member 1 (HSP90AA1)." bioRxiv (2023): 2023-03.
3. Acharyya, S. R., Sen, P., Kandasamy, T., & Ghosh, S. S. (2022). Designing of disruptor molecules to restrain the protein–protein interaction network of VANG1/SCRIB/NOS1AP using fragment-based drug discovery techniques. Molecular Diversity, 1-22.
4. Acharyya, S. R., Sen, P., Kandasamy, T., & Ghosh, S. S. (2022). Dual therapeutic approach to modulate Glycogen Synthase kinase− 3 beta (GSK-3Β) and inhibitor of nuclear factor kappa kinase-beta (IKK-β) receptors by in silico designing of inhibitors. Journal of Molecular Graphics and Modelling, 108225.
5. Kandasamy, Thirukumaran, Plaboni Sen, and Siddhartha Sankar Ghosh. "Multi‐targeted Drug Repurposing Approach for Breast Cancer via Integrated Functional Network Analysis." Molecular Informatics (2022): 2100300.
6. Sain, Arindam, Thirukumaran Kandasamy, and Debdut Naskar. "Targeting UNC-51-like kinase 1 and 2 by lignans to modulate autophagy: possible implications in metastatic colorectal cancer." Molecular Diversity (2022): 1-17.
7. Sain, A., Khamrai, D., Kandasamy, T., & Naskar, D. Targeting protein tyrosine phosphatase 1B in obesity‐associated colon cancer: Possible role of sweet potato (Ipomoea batatas). Proteins: Structure, Function, and Bioinformatics (2022).
8. Sundaramahalingam, M. A., Amrutha, C., Rajeshbanu, J., Thirukumaran, K., Manibalan, S., Ashokkumar, M., & Sivashanmugam, P. In silico approach for enhancing innate lipid content of Yarrowia lipolytica, by blocking the acyl-CoA oxidase-1 enzyme, using various analogous compounds of lipids. Journal of Biomolecular Structure and Dynamics, 1-14 (2021).
9. Barman, S., Roy, A., Bardhan, I., Kandasamy, T., Shivani, S., & Sudhamalla, B. Insights into the Molecular Mechanisms of Histone Code Recognition by the BRPF3 Bromodomain. Chemistry–An Asian Journal, 16(21), 3404-3412 (2021).
10. Sen, Plaboni, Thirukumaran Kandasamy, and Siddhartha Sankar Ghosh. "In-silico evidence of ADAM metalloproteinase pathology in cancer signaling networks." Journal of Biomolecular Structure and Dynamics (2021): 1-16.
11. Sain, Arindam, Thirukumaran Kandasamy, and Debdut Naskar. "In silico approach to target PI3K/Akt/mTOR axis by selected Olea europaea phenols in PIK3CA mutant colorectal cancer." Journal of Biomolecular Structure and Dynamics (2021): 1-16.
12. Jayaraman, Arun Baskaran, Thirukumaran Kandasamy, Dilip Venkataraman, and S. Meenakshisundaram. "Rational design of Shewanella sp. l-arabinose isomerase for d-galactose isomerase activity under mesophilic conditions." Enzyme and Microbial Technology 147 (2021): 109796.
13. Kandasamy, Thirukumaran, Babu Sudhamalla, and Debdut Naskar. "Designing of RNA aptamer against DNA binding domain of the glucocorticoid receptor: A response element-based in-silico approach." Journal of Biomolecular Structure and Dynamics (2020): 1-8.
14. Manibalan, Subramaniyan, Kandasamy Thirukumaran, Mathimaran Varshni, Ayyasamy Shobana, and Anant Achary. "Report on biopharmaceutical profile of recent biotherapeutics and insilco docking studies on target bindings of known aptamer biotherapeutics." Biotechnology and Genetic Engineering Reviews 36, no. 2 (2020): 57-80.
15. Manibalan, Subramaniyan, Ayyachamy Shobana, Manickam Kiruthika, Anant Achary, Madasamy Swathi, Renganathan Venkatalakshmi, Kandasamy Thirukumaran, K. Suhasini, and Sharon Roopathy. "Protein Network Studies on PCOS Biomarkers with S100A8, Druggability Assessment, and RNA Aptamer Designing to Control Its Cyst Migration Effect." Frontiers in bioengineering and biotechnology 8 (2020): 328.
16. Subramanian, Manibalan, Shobana Ayyachamy, Kiruthika Manickam, Swathi Madasamy, Venkatalakshmi Renganathan, Anant Achary, Thirukumaran Kandasamy, K. Suhasini, and Sharon Roopathy. "Identification of target candidate in Polycystic ovarian syndrome and invitro evaluation of therapeutic activity of the designed RNA Aptamer." bioRxiv (2019): 603357.