Research
At Pundir Lab, we study how the innate immune system senses and responds to its environment to maintain tissue health and defend against infection. Our research centers on mast cells, granule-rich, tissue-resident immune cells found at barrier sites such as the skin and mucosa, where they detect host and microbial signals and coordinate immune responses. We focus on how mast cells interpret these signals through cell surface receptors, particularly G protein-coupled receptors (GPCRs), and how this signaling regulates immune activation, inflammation, and homeostasis. Using genetically engineered mouse models, we aim to uncover the mechanisms driving mast cell-mediated immune responses in infection and inflammatory disease.
Theme 1. Cell Surface Receptor Signaling in Mast Cell Activation
A key focus of our group is dissecting how mast cells decode extracellular cues through cell surface receptors, particularly GPCRs such as Mrgprs, distinguishing host from microbe-derived signals and translating them into immune activation, resolution, or tissue remodeling. We investigate this signaling using genetically engineered mouse models, multiparametric flow cytometry, and confocal microscopy, with the goal of identifying receptors that could serve as therapeutic targets in inflammatory and infectious disease.
Theme 2. Mast Cell Surveillance, Neuroimmune Communication, and Tissue Development at Barrier Sites
Our second research area explores how mast cells at the skin and mucosal surfaces monitor their environment, maintain homeostasis, and respond to infection or injury, including cutaneous wound repair, where mast cells are among the first responders shaping the healing process. We also examine how mast cells communicate with the nervous system, focusing on how neuropeptides and microbial ligands influence immune activation and sensory responses, and how the local tissue environment and microbiota shape mast cell maturation, recruitment, and effector function using cell and tissue culture alongside in vivo mouse models.
Theme 3. Mast Cell-Mediated Host Defense in Infection and Inflammatory Disease
Our third research theme addresses how mast cell responses can be protective or pathological depending on context, including central nervous system infection, where meningeal mast cells shape the balance between protective immunity and neuroinflammation during bacterial meningitis. Using mouse and microbial genetics, sequencing, and infection models, we study how mast cells contribute to pathogen clearance and immune regulation, connecting receptor signaling and barrier surveillance to understand when mast cell activation helps versus harms the host.
Skin sections from a Mrgprb2-Cre:tdTomato reporter mouse showing mast cells stained with avidin (green) and tdTomato signal marking Mrgprb2-expressing cells (red). Yellow indicates complete colocalization, confirming that skin mast cells are Mrgprb2⁺.
3D confocal images of avidin-sulforhodamine (red) labeling mast cell granules in whole-mount mouse ears following CSP-1 injection, a quorum sensing molecule from S. pneumoniae (I). Quantification of mast cell degranulation per field of view (J). Scale bar: 50 μm.
Fluorescence microscopy of mouse meninges showing mast cells labelled with avidin (green) and nuclei stained with DAPI (blue). Mast cells cluster along the dural sinus, positioning these immune cells at a critical barrier for brain defense.