My research interests have emerged in the establishment of translational strategies to combat major chronic diseases in humans. The core objective of my research is to establish a fine balance between tolerance and immunity, ultimately preventing inflammation. To achieve this, I explore the potential of utilizing gut microbiome and nutritional therapies as effective interventions against these diseases.
Summary of Research:
1. Microbiome based nutritional therapy: A new arsenal against Toxoplasma gondii treatment induced obesity:
About a third of the world’s population is estimated to be infected by Toxoplasma gondii. This parasite is notorious for its ability to subtly alter human behaviour, even during a latent infection. In individuals with compromised immune systems, T. gondii infections are known to result in loss of vision or severe brain damage. Lack of vaccines and side effects of current treatment methods have kept scientists on the lookout for novel methods to control T. gondii infections. We have delineated a novel paradigm to counter infection caused by an intracellular T. gondii, using small molecules triggering the infected cell’s suicide mechanism, thus killing the parasite residing inside it.
The project based on the disruption of synchrony between gut microbiome and metabolic rhythms by Toxoplasma gondii infection. Competition between symbionts vs pathobiont determines tolerance (Treg/Tr1/Breg/Br1) vs inflammation (Th1/Th17/Inflammatory B1). Chronic infection leads to uncontrolled inflammation towards obesity. This translational research will examine mechanisms of the beneficial effects of probiotics and will discover microbiome based new generation of anti-inflammatory small molecules against T. gondii induced obesity.
2. Antidiabetic drugs can mitigate pan-Covid-19 infection:
In the pandemic situation, the continuum search of therapeutic compound(s) is the preeminent strategy for treating COVID-19 patients. A significant milestone has been reached in my laboratory, as we have made a groundbreaking discovery showing that anti-diabetic drugs have the potential to mitigate SARS-CoV-2 infection. This study reveals that pan-SARS-CoV-2 variants' receptor-binding domain (RBD) interacts with dipeptidyl peptidase-4 (DPP4, other name is CD26), an alternative receptor to ACE2, for viral entry. Our vision is disrupting RBD interactions with DPP4 and ACE2 to prevent all SARS-CoV-2 variants' entry. Advanced structure-assisted drug design and live pan-virus variant research yielded remarkable results. Sitagliptin and linagliptin, conventional diabetic drugs used alone or in combination, effectively suppressed the growth of SARS-CoV-2 variants, including major VOCs (variants of concern) like original SARS-CoV-2, alpha, beta, delta, and kappa clades. The inhibitory effects of sitagliptin and linagliptin on the interaction between the receptor-binding domain (RBD) and both ACE2 and DPP4 receptors demonstrate their potential as promising candidates to circumvent viral replication, offering multifaceted impacts. My team have embarked on a scientific innovation journey to develop effective therapies against pan-SARS-CoV-2 infections. This research not only opens new avenues in the fight against COVID-19 but also plays a significant role in reshaping COVID-19 research, paving the way for a healthier future.
Geetika Kumari, Amit Kumar, Rasmi Ranjan Muduli, Anupamjeet Kaur, Santosh Kumar, Kumod Kumar
• Santa-Cruz Biotechnology (USA) Investigator Award
• Certified Expert of FACS CANTO-II from BD Company, Boston, MA, USA.
• ‘International Travel Grant as Young Scientist’ to Villa-Real, Portugal from DST, Government of India.
• ‘International Travel Grant Award’ to Villa-Real, Portugal from CSIR, Government of India.
• CSIR-SRF (Govt. of India)
• The Best Oral Presentation at 34th Indian Immunology Society Conference-National AIDS Research Institute (NARI), Pune, India.
Independent Fellowship/Faculty Position
• Ramalingaswami Fellowship, DBT, Govt. of India.
• Faculty Recharge Program, UGC, Govt. of India.
- Ahuja R.,* Kaur A., Kumari G., Kumar A., Kumar S., Roy A.K., Majumdar T.* Enhanced expression and solubility of main protease (Mpro) of SARS-CoV-2 from E. coli. (2023) Protein Expression and Purification.
- Mani S, Kaur A, Jakhar K, Kumari G, Sonar S, Kumar A, Das S, Kumar S, Kumar V, Kundu R, Pandey AK, Singh UP, Majumdar T.* (2023) Targeting DPP4-RBD interactions by sitagliptin and linagliptin delivers a potential host-directed therapy against pan-SARS-CoV-2 infections. International J Biological Macromolecules 245:125444.
- Nag S, Mandal S, Majumdar T, Mukhopadhyay S, Kundu R. (2023) FFA-Fetuin-A regulates DPP-IV expression in pancreatic beta cells through TLR4-NFkB pathway. Biochem Biophys Res Commun. 647:55-61.
- Dwivedy A., Mariadasse R., Ahmad M., Chakraborty S., Kar D., Tiwari S., Bhattacharyya S., Sonar S., Mani S., Tailor P., Majumdar T.*, Jeyakanthan J.*, Biswal B.K.* Characterization of the NiRAN domain from RNA-dependent RNA polymerase provides insights into a potential therapeutic target against SARS-CoV-2. PLOS Computational Biology 13;17(9):e1009384, 2021.
- Shelly A., Gupta P., Ahuja R., Srichandran S., Meena J., Majumdar T.* Impact of microbiota: a paradigm for evolving herd immunity against viral diseases. Review article, Viruses, 2020; 12:1150-1173. (based on COVID-19)
- Majumdar T.,* Sharma S., Kumar M., Hussain A.M, Chauhan N., Kalia I., Sahu A.K., Rana V.S., Bharti R., Haldar A.K., Singh A.P., Mazumder S. Tryptophan-kynurenine pathway attenuates β-catenin-dependent pro-parasitic role of STING-TICAM2-IRF3-IDO1 signalosome in Toxoplasma gondii infection. Cell Death & Disease (Nature Group Publisher), 2019;10(161):1-20.
- Srivastava N., Shelly A., Kumar M., Pant A., Das B, Majumdar T., Mazumder S. Aeromonas hydrophilautilizes TLR4 topology for synchronous activation of MyD88 and TRIF to orchestrate anti-inflammatory responses in zebrafish. Cell Death & Discovery (Nature Group Publisher), 2017;3:17067-17076.
- Majumdar T., Dhar J., Patel S., Kondratov R., Barik, S. Circadian transcription factor BMAL1 provides innate immunity against select RNA viruses. Innate Immunity, 2017;23(2):147-154.
- Wang X., Majumdar T., Kessler P., Ozhegov E., Chattopadhyay S., Barik S., Sen GC. STING requires the adaptor TRIF to trigger innate immune responses to microbial infection. Cell Host & Microbe 2016;20:329- 341.
- Suryawanshi A., Manoharan I., Hong Y., Swafford D., Majumdar T., Manicassamy B., Thangaraju M., Koni P.A., Taketo M.M., Manicassamy S. Canonical Wnt Signaling in Dendritic Cells Regulates Th1/ Th17 Responses and Suppresses Autoimmune Neuroinflammation. J. Immunology 2015;194(7):3295-304.
- Majumdar T., Chattopadhyay S., Ozhegov E., Dhar J., Goswami R., Sen G.C., Barik S. Induction of interferon-stimulated genes by IRF3 promotes replication of Toxoplasma gondii. PLOS Pathogens 2015;doi:10.1371/journal.ppat.1004779.g006:1-22.
- Hong Y., Manoharan I., Suryawanshi A., Majumdar T., Angus-Hill M.L., Koni P.A., Manicassamy B., Mellor A.L., Munn D.H., Manicassamy S. β-catenin promotes regulatory T-cell responses in tumors by inducing vitamin A metabolism in dendritic cells. Cancer Research 2015;75:656-665.
- Majumdar T.,* Goswami R.,* Dhar J., Chattopadhyay S., Bandyopadhyay S.K., Verbovetskaya V., Sen G.C., Barik S. Viral degradasome hijacks mitochondria to suppress innate immunity. Cell Research 2013;23(8):1025-1042. *co-first author
- Musiyenko A., Majumdar T., Andrews J., Adams B., Barik S. PRMT1 methylates the single Argonaute of Toxoplasma gondii and is important for the recruitment of Tudor nuclease for target RNA cleavage by antisense guide RNA. Cellular Microbiology 2012;14:882-901.
- Haque S.J., Majumdar T., Barik S. Redox-assisted protein folding systems in eukaryotic parasites. Antioxidant Redox Signal. 2012;15:674-83.
- Swedan S., Andrews J., Majumdar T., Musiyenko A., Barik S. Multiple functional domains and complexes of the two nonstructural proteins of human respiratory syncytial virus contribute to interferon suppression and cellular location. J. Virology 2011;85:10090-100100.
- Majumdar T., Das B., Bhadra R.K., Dam B., Mazumder S. Complete nucleotide sequence of a quinolone resistance gene (qnrS2) carrying plasmid of Aeromonas hydrophilaisolated from fish. Plasmid 2011;66:79-84.
- Jayaswal S., Kamal M.K., Dua R., Gupta S., Majumdar T., Das G., Kumar D., Rao K.V.S. Identification of host-dependent survival factors for intracellular Mycobacterium tuberculosis through an siRNA screen. PLOS Pathogens 2010;6:1-15.
- Majumdar T., Das B., Mazumder S., Bhadra R.K. Complete sequence of the quinolone resistance gene carrying plasmid pBRST7.6 from the fish pathogen Aeromonas hydrophila. NCBI, Gene Bank Accession No. EU925817;2008.
- Majumdar T., Chattopadhyay P., Saha D.R., Sau S., Mazumder S. Virulence plasmid of Aeromonas hydrophilainduces macrophage apoptosis and helps in developing systemic infection in mice. Microbial Pathogenesis 2009;46:98-107.
- Majumdar T., Datta S., Ghosh D., Dutta S., Chakraborty A., Goswami R., Mazumder S. Role of virulence plasmid of Aeromonas hydrophilain the pathogenesis of ulcerative disease syndrome in Clariasbatrachus. Indian J. Biochemistry Biophysics 2007;44:401-406.
- Datta S., Saha D.R., Ghosh D., Majumdar T., Bhattacharya S., Mazumder S. Sub-lethal concentration of arsenic interferes with the proliferation of hepatocytes and induces in vivo apoptosis in ClariasbatrachusL. Comparative Biochemistry Physiology 2007;145:339-349.
- Majumdar T., Ghosh D., Datta S., Sahoo C., Pal J., Mazumder S. An attenuated plasmid cured strain of Aeromonas hydrophilaelicits protective immunity in ClariasbatrachusL. Fish & Shellfish Immunology 2007;23:222-230.
- Majumdar T., Ghosh S., Pal J., Mazumder S. Possible role of a plasmid in the pathogenesis of a fish disease caused by Aeromonas hydrophila. Aquaculture 2006;256:95-104.