NON-COMMUNICABLE DISEASES / Immunology
Research Interests
Adaptive immunity to Mycobacterium tuberculosis, Vaccine formulation against Tuberculosis, T cell biology, Immunotherapy for Tuberculosis.
Description of Research
The lab investigates the spectrum of cellular and molecular bases underlying protective and pathogenic immune responses across various infectious disease models. The aim is to identify the immunological defences that govern host-pathogen interactions.
Tuberculosis has been an age-old disease, yet it still affects one-fourth of the world’s population. The anti-tuberculosis therapy is cumbersome and the only licensed vaccine, BCG is more than a century old and poses to be inefficacious in the adult population. Owing to this conjecture, our laboratory works on various novel strategies to develop immunological interventions that preferentially amplify protective immune responses while suppressing the immunoregulatory pathways that compromise host resistance to TB. One such work is to investigate the mechanism of immunomodulatory agents which can suffice as an adjunct to the current anti-TB therapy and overcome the boundaries of current therapeutics. We also work on the unconventional T cell subsets that interface the immune regulation, focusing on how their functional impairment drives TB progression and how their selective modulation can augment host response.
The lab also focuses on developing potential vaccine candidates with optimized adjuvant formulations and heterologous prime-boost regimens to establish durable tissue-resident immunity in adult populations. Our investigations focus on overcoming BCG-induced immune tolerance and generating sterilizing or durable clinical immunity through mechanistic evaluation of T cell differentiation, functional antibody responses, and mucosal immune priming. We also focus on characterizing the distinctive immune convolutions of Mycobacterium tuberculosis in its unconventional niches causing extrapulmonary TB, to identify therapeutic targets and biomarkers of risk. Through these integrated programs, we aim to translate immunological insights into rational strategies for TB prevention and treatment.
Use of novel immunomodulators as an adjunct therapy against TB. As an immunomodulator, Bergenin activates MAPK signaling pathways in the macrophages leading to the induction of NF-κB, which in turn results in the expression of protective pro-inflammatory cytokines and iNOS. The NO thus produced mediates the killing of intracellular mycobacteria and the pro-inflammatory cytokines activate Th cells, which mediates further protection.
Recent Publications
Pahuja I, Ghoshal A, Okieh AA, Verma A, Negi K, Agarwal M, Chandra NS, Sharma SK, Bhaskar A, Dwivedi VP. Immunoinhibitory effects of anti-tuberculosis therapy induce the host vulnerability to tuberculosis recurrence. Microbiol Spectr. 2024 Jul 2;12(7):e0041224.
Agarwal M, Bhaskar A, Singha B, Mukhopadhyay S, Pahuja I, Singh A, Chaturvedi S, Agarwal N, Dwivedi VP, Nandicoori VK. Depletion of essential mycobacterial gene glmM reduces pathogen survival and induces host-protective immune responses against tuberculosis. Commun Biol. 2024 Aug 6;7(1):949.
Mukhopadhyay S, Pahuja I, Okieh AA, Pandey D, Yadav V, Bhaskar A, Dwivedi VP. Bergenin potentiates BCG efficacy by enriching mycobacteria-specific adaptive memory responses via the Akt-Foxo-Stat4 axis. Tuberculosis (Edinb). 2024 Jul;147:102517.
Pahuja I, Verma A, Ghoshal A, Mukhopadhyay S, Kumari A, Shaji A, Chaturvedi S, Dwivedi VP, Bhaskar A. Biapenem, a Carbapenem Antibiotic, Elicits Mycobacteria Specific Immune Responses and Reduces the Recurrence of Tuberculosis. Microbiol Spectr. 2023 Aug 17;11(4):e0085823.
Bhaskar A, Pahuja I, Negi K, Verma A, Ghoshal A, Mathew B, Tripathi G, Maras JS, Chaturvedi S, Dwivedi VP. SIRT2 inhibition by AGK2 enhances mycobacteria-specific stem cell memory responses by modulating beta-catenin and glycolysis. iScience. 2023 Apr 10;26(5):106644.
Kumari A, Pahuja I, Negi K, Ghoshal A, Mukopadhyay S, Agarwal M, Mathew B, Maras JS, Chaturvedi S, Bhaskar A, Dwivedi VP. Withaferin A Protects against Primary and Recurrent Tuberculosis by Modulating Mycobacterium-Specific Host Immune Responses. Microbiol Spectr. 2023 Mar 14;11(2):e0058323.
Group Leader
Ved Prakash Dwivedi
ICGEB New Delhi, India
E-mail: [email protected],
[email protected]
Tel: +91-11-26741358/ 26741361/ 26742357/ 26742360 ext. 427
Group Leader CV
Group Members
Ashima Bhaskar, Research Scientist
Isha Pahuja, Post Doctoral Fellow
Akanksha Verma, PhD Student
Aishwarya Shaji, PhD Student
Ahmed Abdallah Okieh, PhD student (BIOTECHNET Fellow)
Suparba Mukhopadhyay, PhD Student
Ravikant Yadav, PhD Student
Satya Banger, PhD Student
Juhi Srivastava, PhD Student