Research Interests:Hemostasis is the focus of my research. Our lab is interested in four major areas:
Platelet type- von Willebrand disease (PT-VWD):
Mutations in the platelet GP1BA gene causing this rare autosomal dominant bleeding disorder. I have identified and characterized a novel mutation in the macroglycopeptide region of the GP1BA gene in three members of a British family with PT-VWD phenotype and has coordinated an international project for the differential identification between the two closely similar disorders type 2B and PT-VWD based on genetic analysis . The results of this project is now published. For more info on pervious and ongoing related work please refer to http://www.pt-vwd.org/. We are currently investigating the bleeding phenotype in patients with PT-VWD worldwide, participating in international study using flowcytometry to differentiate type 2B VWD form PT-VWD as well as conducting a novel focused group of investigation in the PT-VWD mouse model including assessing the bleeding phenotype using thromboelastography during pregnancy and in response to infection as well as investigating novel treatment modalities.
Thromobelastography (TEG) studies:
We have demonstrated a wide inter and intra individual variations in the TEG pattern in hemophilia A dogs. We have also shown that acute exercise improves the global hemostatic efficacy in those hemophilic animals as shown by the changes in their TEG patterns. We evaluated the role of thromboelastography as a sensitive hemostatic tool to monitor the rFVII treatment in hemophilia A dogs. We are also investigating the role of TEG in determining haemostatic abnormalities in two medical conditions: Obstructive sleep apnea (OSA) and pre eclampsia. We are studying the TEG changes following inspiratory occlusion in anaesthetized rats to model OSA and also in LPS- treated pregnant rats to model pregnancy complication. We are currently investigating the effect of CPAP treatment on hypercoagulability in patients with severe OSA using a cross blinded study.
Prostate cancer and thrombosis:
We have recently extended our TEG studies to include prostate cancer investigating the role of this sensitive global assay in assessing hypercoagulability in these patients as well as novel markers that help risk stratification and guidance to anticoagulant prophylaxis. These studies are performed in collaboration with Dr. Rob Siemens. Currently we are studying the role of hypoxia in tumor microenvironment as well as the ADT therapy in thromboembolic risk in these patients.
Platelet- adenovirus interactions
We investigated the mechanism of acute thrombocytopenia that follows adenovirus administration and approaches to prevent this adverse effect. We have demonstrated a novel expression of CAR on human platelets and a critical role for the platelet P-selectin and the VWF protein in mediating adenovirus induced platelet clearance and currently studying the detailed adenovirus/ platelet interactions (binding/ internalization) both in vitro using human platelets and in vivo using mice platelets. We have studied the interaction of platelets with inert particles and compared it to adenovirus including the effect on platelet aggregation and the role of platelet membrane receptors as well as the ultrastructure of platelets in response to adenovirus. We are currently investigating approaches to reduce the adenovirus induced thrombocytopenia and their effect on virus liver transduction.