AC

Arijit Chakraborty

Massachusetts General Hospital, Indian Institute of Chemical Biology CSIR

ORCID iD 0000-0002-0883-6385
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About

My long-term research goal is to define how bacterial pathogens actively reprogram host immune cell metabolism and chromatin states to promote persistence, and to leverage this knowledge to develop host-directed strategies to prevent or reverse chronic infection. During my doctoral training, I investigated host–pathogen interactions in bacterial and protozoan infection models and established non-canonical Wnt5a signaling as a key regulator of macrophage antimicrobial function, cytoskeletal remodeling, and immune homeostasis. This work provided my foundation in macrophage biology, immune regulation, molecular and cellular immunology, animal models of infection, and advanced imaging and flow cytometry. Building on this foundation, my postdoctoral research at Massachusetts General Hospital in the laboratory of Dr. Laurence G. Rahme, I shifted my focus toward pathogen-derived small molecules as active modulators of host immunity. I discovered that the Pseudomonas aeruginosa quorum-sensing metabolite 2-aminoacetophenone (2-AA) induces macrophage tolerization by rewiring lipid metabolism, autophagy, mitochondrial bioenergetics, and chromatin accessibility. Mechanistically, 2-AA suppresses intracellular bacterial clearance through HDAC1-dependent chromatin remodeling, reduced acetyl-CoA availability, and altered histone acetylation and lactylation, establishing a metabolic–epigenetic axis of immune tolerance. Using CUT&RUN, RNA-seq, metabolic profiling, and organ-on-chip infection models, I further demonstrated that these pathogen-induced epigenetic and transcriptional programs are durable yet reversible, highlighting therapeutic opportunities to restore host immune function. My ongoing work defines how pathogen-derived metabolites establish epigenetic memory in innate immune cells and how this memory can be therapeutically manipulated in chronic and immunocompromised settings. Across my doctoral and postdoctoral work, I have defined how pathogens exploit host signaling, metabolism, and chromatin architecture to evade immunity and establish persistence. My contributions bridge basic immunology and translational research and form the foundation of my independent research program focused on pathogen-induced epigenetic memory and immunometabolic tolerance. A key goal of my research is to develop host-directed strategies to reverse pathogen-induced immune tolerance through metabolic modulation and small-molecule inhibitors. This program is conceptually and technically distinct from my postdoctoral training and is designed to be executed with modest resources, leveraging my expertise in epigenetic profiling, metabolic assays, bacterial infection models, and organ-on-chip platforms. Collectively, my work aims to bridge basic immunology and translational science by uncovering mechanisms through which pathogens exploit host metabolic and epigenetic programs, laying the groundwork for therapeutic strategies that complement conventional antimicrobial approaches.

Employment

  • Massachusetts General Hospital Post Doctoral Research Fellow
    2019 - Present
  • Indian Institute of Chemical Biology CSIR Graduate Student
    2010 - 2018

Education

Education history is unavailable.

Projects & Funding

Projects & funding information is unavailable.

Publications (11)