Naveen Manchanda, MD
New details in the field of hemostasis and thrombosis emerge continually. From doubts regarding the possibility of elucidating the coagulation cascade in the 1960s to today’s increasingly clear evidence of the various proteins involved in this cascade, there has been a sea-change in our understanding of this cascade.
Apart from being a mere collection of clotting proteins, we know that the proteins in this cascade include anticoagulants, fibrinolytic proteins and fibrinolysis inhibitors, cell surface receptors, immunological modulators, and a host of other molecules that mediate several other functions. As a fitting finale to this exciting meeting, several talks will be presented in this session that will explore various aspects of this cascade.
Anticoagulant proteins have been extensively studied to see if they could temper the imbalanced coagulation response in sepsis. Activated protein C (APC) was one of the anticoagulant proteases found to be effective, having an anticoagulant as well as an anti-inflammatory response. The mechanism underlying this anti-inflammatory response is not clear. Researchers from the Oklahoma Medical Research Foundation will present data showing the involvement of histones in mediating sepsis-associated organ damage. They will also show in vitro and in vivo models of APC blocking this toxicity by cleaving histone proteins. Whether accelerated cleavage of these proteins can prevent the protean manifestations of sepsis is a question that will be further explored.
Stimulated integrin receptors serve many functions including adhesion, protein binding, signaling, and cell trafficking, among others. The precise mechanism of integrin activation by a specific platelet agonist has not been ascertained. Dr. Mark Ginsberg of the University of California – San Diego will present elegant studies showing that Talin can bind and activate unclustered GPIIβ-IIIα receptors. This process requires Talin to interact with the phospholipid membrane. Whether this Talin-integrin interaction can be modulated to control platelet aggregation will be discussed.
Dr. Katherine High from the Children’s Hospital of Philadelphia will outline advances in gene therapy for hemophilia. This endeavor fascinates, inspires, and engages legions of researchers. Hemophiliac beings of the canine variety have been serving their scientist masters dutifully and were instrumental in showing success of liver transduction as well as expression of hemophilia B (factor IX) genes. This work has been extended to humans over the past decade and there has been continuing excitement over preliminary success of this technique in increasing factor levels to a safe range. However, the challenges of ensuring long-term factor expression and making the vector less immunogenic remain. Studies will be presented showing how improvements in technique have developed. The possibility that other hemophilia proteins could be targeted for expression in this fashion will also be discussed.
The Corvette of coagulation — this may be the name given to platelets in their unquenched desire to speedily form a blood clot. Unlike the soluble clotting system, we have no easily controllable mechanism of modulating platelet activity. The question remains how to preserve hemostasis while inhibiting platelet associated thrombosis. Dr. Louisa Dowal will present data about the G Protein-coupled receptor (GPCR) system in platelets and will show that the GPCR receptor signaling system can be interrupted to accomplish slowing of platelet thrombotic functions.
Plan to attend this special symposium taking place in Valencia D of the Orange County Convention Center.
Dr. Manchanda indicated no relevant conflicts of interest.