Analysis of clotting across species, from phage to fish to mammals
Disorders of blood clotting (both too much and too little) are responsible for significant morbidity and mortality, affecting millions of patients on a yearly basis. The coagulation cascade has been well studied over the last half century, yet there are still elements of initiation of the intrinsic and extrinsic pathways that are not fully understood. Our objective is to use innovative technologies, including phage display and the zebrafish model, to study these pathways both in vitro and in vivo. Using these techniques, we have previously shown the ability to map protein domains and identify critical residues in vitro and in vivo. We will extend this work to the study of polyphosphate binding protein, a critical mediator of intrinsic pathway initiation by polyphosphate, as well as tissue factor (TF), the protein responsible for initiation of the extrinsic pathway.