MEDICAL BIOTECHNOLOGY / Recombinant Diagnostics and Vaccines
The group’s long-term interest is to develop an alternate, preferably non-invasive method of disease diagnosis that could be useful at a point-of-care facility with limited resources. The immediate focus is to profile and identify important features (e.g. proteins, volatile organic compounds or miRNA) from different biofluids of humans, collected from collaborative clinical sites representing diverse geographical locations. The group employs robust multidimensional gas/liquid chromatography and mass spectrometry techniques to identify and quantify micro/macro molecular constituents of biofluids of tuberculosis active and suspect study groups. Comparative proteomics and metabolomics tools with system biology approaches are employed to identify important molecular constituents and their biological significance to explain disease specific perturbed conditions. The group’s phase-I/II breath based biomarker discovery work shows promising results, which will hopefully be translated to develop a POC test in the format of eNOSE in the coming years.
Tuberculosis, Immunology, Proteomics, Metabolomics, Metallomics, Therapeutics
Description of Research
Anemia of inflammation in Tuberculosis: Iron is a critical component for the basic survival of both host and pathogen. The host has evolved a complex mechanism involving major proteins (hepcidin, ferroportin, transferrin, DMT1, Nramp1, ferritin and others) to limit access of iron for pathogen survival. In parallel, the pathogen has also developed a strategy to alternately acquire or retain iron in anaemic conditions. The group’s preliminary data suggest that existing approved metal chelators could be useful for further limiting iron access to Mycobacteria for its survival in infected mice model systems and exploring their mechanism of action at molecular levels.
Contribution of immuno-senescence (in ageing) and chronic inflammation (in diabetes) to tuberculosis susceptibility: Ageing leads to profound changes in the body’s immune milieu, causing immune-senescence, and significantly increases a person’s susceptibility to reactivation of latent disease, or rapid progression to active tuberculosis (TB) disease. Reports showed decreased neutrophil count and monocyte functions, altered function in peripheral T lymphocytes and loss of naive T cells in aged mice models and humans. The group aims to understand and correlate the age-associated decline in immunological parameters and its contribution to TB susceptibility in human and in murine models of TB representing varied age groups. While type 2 diabetes mellitus (T2DM) has long been associated with a higher risk for TB infection and adverse disease outcomes, the underlying mechanisms of this susceptibility are poorly understood. In this project, using patients and animal models, we will try to understand the core mechanisms ruling the immune insufficiency in TB-DM at the cellular and molecular levels. Understanding the altered host immunity in aged and T2DM subjects might be useful to develop age or TB-DM appropriate therapeutic solutions for these co-morbid TB patients.
Alveolar type-II epithelial cells as niche for Mycobacterium survival: Like immune cells, type-II epithelial cells also represent a niche for Mycobacterial infection. The group uses optimised methods for infecting alveolar epithelial cell lines (A549) with different laboratory and clinical Mycobacterial strains to monitor the intermediates of central carbon metabolism and to probe the mitochondrial functional dynamics. The group employs carbon labelling (13C) and flux balance analysis (FBA) to monitor the glycolysis, TCA cycle and OXPHOs metabolism in control and infected A549 cells. Using inhibitors, the group aims to identify the critical host metabolic pathways to eliminate pathogens by modulating the energy kinetics.
Gut microbiota and their byproducts as nutrient supplements in tuberculosis: Employing metagenomics and metabolomics tools, the group observed microbial dysbiosis and deregulated fecal metabolites in tuberculosis patients and in in vivo model systems which partially resolve during therapeutic interventions. The group is confident to demonstrate the importance of gut microbiota and its by-products in resolving infectious disease conditions like tuberculosis.
Developing eNOSE for tuberculosis screening: Using exhaled breath volatile organic compounds as markers, the group is collaborating with a start-up company and an established player in this field with expertise in sensor, electronics designing and decision-making tools. The group is in the process of developing an eNOSE for further refinement and testing with clinical collaborators in India.
Meitei, H.N., Pandey, A., Faruquee, HMd., Thokchom, M., Athokpam, S., Guha, H., Das, R., Saha, S., Kupa, R., Kapfo, W., Keppen, J., Mohapatara, A.K., Priyadarsini, H., Koijam, A.S., Dasgupta, A., Goswami, B., Thong, A., Meru, K., Konyak, W., Gupta, D., Das, A., Khamo, V., Huidrom, L.S., Haobam ,S., Nanda, R.K., Haobamm R. 2021. Polymorphism of NAT2, PXR, ABCB1, and GSTT1 genes among tuberculosis patients of North Eastern States of India. medRxiv 2021.06.09.21258600; doi: https://doi.org/10.1101/2021.06.09.21258600
Faruquee, HMd,, Meitei, H.N., Pandey, A., Pahwa, F., Thokchom, M., Sonia, A., Chaudhary, S., Gupta, D., Singh, H.L., Haobam, S., Haobam, R., Nanda, R.K. 2021. Urine metabolome of tuberculosis patients receiving intensive phase of treatment show diurnal variations. medRxiv, doi: https://doi.org/10.1101/2021.03.30.21254606
Mohapatra, P., Shriwas, O., Mohanty, S., Kaushik, S.R., Arya, R., Rath, R., Majumdar, S.K.D., Muduly, D.K., Nanda, R.K., Dash, R. 2021. CMTM6 drives cisplatin resistance in OSCC by regulating AKT mediated Wnt signaling. bioRxiv 2020.03.18.993774; doi: https://doi.org/10.1101/2020.03.18.993774. JCI Insight 6(4):e143643 PubMed link
Shriwas, O., Arya, R., Mohanty, S., Kumar, S., Rath, R., Kaushik, S.R., Thakur, M.C., Pahwa, F., Majumdar, S.K.D., Muduly, D.K., Nanda, R.K., Dash, R. 2021. RRBP1 rewires cisplatin resistance in Oral Squamous Cell Carcinoma by regulating YAP-1. bioRxiv 2020.03.18.998070; Br J Cancer 124(12):2004-2016. https://doi.org/10.1038/s41416-021-01336-7
Arya, R., Dabral, D., Faruquee, H.M., Mazumdar, H., Patgiri, S.J., Deka, T., Basumatary, R., Kupa, R., Semy, C., Kapfo, W., Liegise, K., Kaur, I., Choedon, T., Kumar, P., Behera, R.K., Deori, P., Nath, R., Khalo, K.P., Saikia, L., Khamo, V., Nanda, R.K. 2020. Serum Small Extracellular Vesicles Proteome of Tuberculosis Patients Demonstrated Deregulated Immune Response. Proteomics Clin Appl 14,1,1900062 PubMed link
Meher, A., Guha, H., Pemmadi, R.V., Akram, S., Faruquee, H.M., Arya, R., Ghosh, H., Nikam, C., Saha, S., Das, R., Dasgupta, A., Goswami, B., Gupta, D., Das, A., Nanda, R.K. 2020. Whole-Genome sequence of drug-resistant Mycobacterium tuberculosis strain S7, isolated from a patient with pulmonary tuberculosis. Microbiol Resour Announce 9,17,e01567-19 PubMed link