The Simon laboratory studies the innate immune mechanisms governing inflammation, infection, and atherosclerosis. The onset of vascular inflammation is the interaction between circulating leukocytes and endothelial cells, where they attach to the wall of a blood vessel and migrate into effected tissue. Our laboratory develops technologies to delve the force and molecular dynamics by which monocytes and neutrophils recruit to inflamed endothelium and migrate to the site of tissue insult. Imaging technologies are developed to delve the multistep sequence by which leukocytes roll-arrest and transmigrate to a site of acute inflammatory tissue insult. Our strategy is to mimic the hydrodynamic shear, chemokine gradients, and adhesion molecule presentation using recombinant protein substrates and endothelial monolayers in microfluidic based lab-chip devices to provide a means of studying complex cell signaling and mechanoregulation in reduced systems accessible to real-time observation. Three active NIH R01 grants fund the labs activity:
- Outside-In Mechanotransduced Inflammatory Targets: The premise is that acquiring a deeper knowledge of how selectin and integrin receptors use tensile bond force to convert biochemical signals to synchronize a suite of functional responses, we can better target drugs to ameliorate inappropriate inflammation while maintaining critical immune responses.
- Engineering the Innate Immune Response to Staphaureus Infection: Host and microbial factors enhance myeloid differentiation of hematopoietic stem cells and fortify antimicrobial functions of expanded PMN against drug resistant Staphaureus. This host response can be engineered to hasten clearance and improve wound healing. To test this hypothesis we employ an innovative in-vivo immunofluorescence imaging approach to noninvasively monitor PMN recruitment and local expansion while manipulating these processes to facilitate SA clearance and wound resolution.
- An Integrated In Vitro 3D Model of Human Bone Marrow and Peripheral Infection: Our premise is that by creating a perfused microfluidic-based vascular network with a functional bone marrow, we can incorporate the essential components of the innate immune response, including scale, dilution, transport barriers, and vascular dynamics, and address key questions such as: What are the signals that mobilize HSPCs from the bone marrow into the peripheral circulation and to the site of infection?