Molecular mechanisms of leukocyte adhesion and trafficking
Leukocyte adhesion cascade
Integrin activation at the footprints of neutrophils. Movie: TIRF imaging of neutrophil-like HL-60 cell rolling and arrest under flow. CMDR: cell membrane. TagRFP-K3: kindlin-3 labeled with TagRFP, mAb24-AF488: antibody reporter of high-affinity β2 integrin. Flow direction: top to down. 0 s, cell arrest. < 0 s, cell rolling. > 0 s, cell adhesion. Scale bar, 5 µm.
Visualization of neutrophil recruitment and function during inflammation
Neutrophils circulating in the bloodstream are first captured by the vessel wall, followed by rolling, slow rolling, full activation, and arrest, before transmigration across the vessel wall. In response to inflammation, receptor ligation on the membrane of immune cells is transmitted by intracellular second messengers. We develop and apply tools including reporter mice for cAMP/cGMP/Ca2+ and β2 integrin activation to understand inter- and intra-cellular signaling responding to inflammatory signals.
β2 integrin activation in vivo. Movie: Mouse neutrophils arrest on the vessel wall in response to CXCL1. Reporter antibodies show extended integrin (red, top) and high-affinity integrin conformation (green, middle). Channel merge shown in yellow (bottom). Purple, neutrophil cell outline.
Engineering immune cells for cancer immunotherapy
We use a variety of approaches to test our hypotheses and to achieve our goals.