Dr. Margaritis's research pivots on a unique model he and his team developed, whereby they can enhance the extrinsic pathway of coagulation by raising the circulating levels of activated FVII (FVIIa) in animal models. Such an approach has obvious ramifications as a potential treatment for coagulation disorders that are currently treated with recombinant FVIIa.

In a series of novel experiments in life models with hemophilia, Dr. Margaritis showed that expression of FVIIa via gene transfer results in dramatic phenotypic improvements or complete correction. In addition, he and his lab team developed mouse- and canine-specific reagents, assays, and endpoints that allow for monitoring the in vivo effects in hemostasis resulting from the action of FVIIa. A current line of investigation aims to better define the intricacies of viral transduction-based FVIIa gene expression and its hemostatic effects in animal models of hemophilia.

The general concept of coagulation proteases interacting with factors other than their natural ligands also applies to FVIIa. Its binding to cell-surface receptors other than tissue factor poses intriguing questions on previously unconsidered interactions affecting its function. As a result, part of Dr. Margaritis's ongoing work is a new line of investigation that focuses on the molecular interactions between FVIIa and its binding partners and how these relate to the hemostatic and other role(s) of FVIIa in vivo. To address these functions he has developed unique in vitro and in vivo methodologies to define, quantitate, and even visualize FVIIa-participating reactions as they occur in real time. Exploiting this information may also form the basis for the rational design FVIIa-based therapeutics, either protein or gene-based, that can be used for the treatment of coagulation defects.

BSc, The University of Newcastle-upon-Tyne (Genetics), 1995

DPhil, The University of Oxford (Molecular Biology and Gene Therapy), 2000

Investigator

Research Assistant Professor of Pediatrics

Faculty of 1000, 2009-

International Society of Thrombosis and Haemostasis, 2009-

American Society of Gene and Cell Therapy, 2009-

American Society of Hematology, 2009-

American Heart Association, 2013-

North American Society of Thrombosis and Hemostasis, 2014-

Grifols Martin Villar Haemostasis Award, 2015