Our lab is interested in the molecular mechanisms that regulate neutrophil activation.
Neutrophils are the most abundant leukocyte in humans. During infection, swarms of neutrophils migrate toward pathogens where they secrete cytokines to amplify the inflammatory response and kill microorganisms through phagocytosis and release of toxic mediators including reactive oxygen species, granule enzymes and neutrophil extracellular traps. Neutrophils are critical for host defense; however, aberrant and/or prolonged neutrophil activity can also inflict devastating tissue damage in inflammatory conditions. Calcium is an evolutionarily conserved signaling messenger that is a central component of multiple signaling pathways.
In immune cells, increases in cytoplasmic calcium are controlled via store-operated calcium entry where calcium release-activated calcium channels allow influx of extracellular calcium when endoplasmic reticulum stores are depleted. STIM proteins are ER calcium “sensors” which sense calcium depletion and directly gate ORAI, a pore subunit of the CRAC channel. We use genetic and pharmacological approaches to study how STIM and ORAI molecules regulate calcium entry to direct neutrophil activation. New projects focus on how other ion channels interact with and modulate calcium-dependent neutrophil activation.
2: Identify molecular targets to manipulate neutrophil activation during infection and inflammation
Projects
- Role of STIM and ORAI-mediated calcium flux in neutrophil migration and “swarming” behavior
- Membrane potential as a unique determinant of neutrophil subpopulations during development and disease
- Mechanisms of neutrophil evasion by bacterial pore-forming (ion channel-like) toxins
- STIM and ORAI-mediated calcium flux in acute lung injury