Karthik Subramanian, PhD

Scientist E-I

Research Programs

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The first major research stream focuses on host extracellular vesicles (EVs), small membrane-bound particles released by cells that carry proteins, nucleic acids, and lipids. During bacterial infections, EVs become rich repositories of both host and pathogen signatures. The laboratory has shown that pneumococcal infection induces distinct EV populations that package bacterial antigens along with immune-response proteins. These EVs actively participate in shaping the host response rather than passively carrying cargo alone. Their cargo reflects disease state, severity, and tissue involvement, making them valuable candidates for biomarker discovery. Moreover, because EVs naturally deliver biological material to immune cells, they offer an attractive platform for presenting antigens or modulating immunity in a controlled way. This work forms the basis of ongoing efforts to identify EV-derived diagnostic markers and to engineer EVs as next-generation immunotherapeutic tools.

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The second research thrust is a recently started research program that explores how immune-cell populations in the lower respiratory tract respond differently to pneumococcal carriage versus pneumonia. In its commensal state, S. pneumoniae resides in the nasopharynx as a biofilm attached to the epithelium, causing minimal inflammation. However, when it reaches the lungs, the same organism triggers an intense and often damaging immune reaction. This project aims to map these contrasting immune landscapes using mouse models, examining the composition of immune-cell subsets, their gene-expression profiles, and the cytokine environments that distinguish benign colonization from invasive disease. By determining how the immune system tolerates pneumococcus in one site yet reacts aggressively in another, this work will help clarify what triggers disease progression. Such insights are essential for designing interventions that prevent pneumonia while respecting natural microbial carriage, and they align closely with the lab’s broad interest in immune–pathogen dynamics.

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The third research stream integrates two complementary efforts: systematic drug repurposing to suppress pneumococcal virulence and a new collaborative initiative with Dr. Nagarjun Narayanaswamy, Transdisciplinary program to develop advanced DNA aptamer-based diagnostic tools to differentiate 100 serotypes of S. pneumoniae. The drug-repurposing project screens FDA-approved or clinically investigated compounds to identify small molecules that disrupt key virulence pathways rather than total bacterial killing. By focusing on molecules that interfere with adaptation, toxin activity, or other disease-critical mechanisms, the lab aims to develop anti-virulence interventions that avoid the selective pressure associated with traditional antibiotics. Because many of the screened compounds already have established safety and pharmacokinetic profiles, promising candidates can advance more rapidly through preclinical evaluation. This strategy combines speed, safety, and mechanistic precision, offering an efficient route to new therapeutics against pneumococcal disease.

Current Research Grants

  • 2029 2026

    Title: Identification of Novel Extracellular Vesicle-Associated Bacterial Antigens and Host Biomarkers in Bacterial Pneumonia.
    Project budget: Rs. 14,946,235.32
    Indian Council of Medical Research [ICMR]

  • 2026 2021

    Ramalingaswami Fellowship
    Title: Investigating pneumococcal adaptation to intracellular survival within the host and characterization of macrophage extracellular vesicles for novel vaccine development.
    Department of Biotechnology [DBT]

  • 2026 2021

    Disarming bacterial pathogens using novel peptides that target pore-forming toxins: from in silico to in vivo
    Department of Science & Technology [DST]

Previous/ Completed Research Grants

    1. Unravelling bacterial immunoevasion and host immune reprogramming strategies in invasive pneumococcal diseases.
      DST-SERB Start-up Grant [SRG] 2021-2023

    2. Developing novel host-derived peptides to neutralize bacterial pore-forming toxins in bacteremic patients
      Karolinska Institutet, Stockholm, Sweden 2018-2020