Paris Margaritis, DPhil

Paris Margaritis, DPhil

Paris Margaritis, DPhil, is a researcher in the Division of Hematology at The Children's Hospital of Philadelphia.

Locations: Main Campus
Appointments and Referrals: 1-800-TRY-CHOP (1-800-879-2467)

Background

Our research pivots on a unique model that we have developed, whereby we 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. Indeed, in a series of novel experiments in life models with hemophilia, we showed that expression of FVIIa via gene transfer results in dramatic phenotypic improvements or complete correction. In addition, we developed mouse and canine-specific reagents, assays and endpoints that allow us to monitor in vivo effects in hemostasis resulting from the action of FVIIa. A current line of investigation in our laboratory 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 pose intriguing questions on previously unconsidered interactions affecting its function. As a result, part of ongoing work in our laboratory 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 we have 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.

Education and Training

Additional Training

Postdoctoral Fellow - The Children's Hospital of Philadelphia, Philadelphia, PA

Undergraduate Degree

BSc in Genetics - The University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, UK

Graduate Degree

DPhil in Molecular Biology and Gene Therapy - The University of Oxford, Oxford, UK

Titles and Academic Titles

Researcher

Research Assistant Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania

Departments and Services

Publications

Papers

2016

Marcos-Contreras Oscar A., Smith Shannon M., Bellinger Dwight A., Raymer Robin A., Merricks Elizabeth, Faella Armida, Pavani Giulia, Zhou Shangzhen, Nichols Timothy C., High Katherine A., Margaritis Paris: Sustained correction of FVII deficiency in dogs using AAV-mediated expression of zymogen FVII. Blood 127(5): 565, Feb 2016.

2014

Pavani Giulia, Ivanciu Lacramioara, Faella Armida, Marcos-Contreras Oscar A. and Margaritis Paris: The endothelial protein C receptor enhances hemostasis of FVIIa administration in hemophilic mice in vivo. Blood 124(7): 1157-65, Aug 2014.

Balestra Dario, Faella Armida, Margaritis Paris, Cavallari Nicola, Pagani Franscesco, Bernardi Franscesco, Arruda Valder R., Pinotti Mirko: An engineered U1 small nuclear RNA rescues splicing-defective coagulation F7 gene expression in mice. Journal of Thrombosis and Haemostasis 12(2): 177-85, Feb 2014.

Abstracts

2016

Hay Chuck, Ewing Laura, Fantegrossi William E., Hambuchen Michael, Reichard Emily, Margaritis Paris, Zhou Shangzhen, and Peterson Eric C.: Design and Testing of Long Acting Viral Mediated Anti-METH Immunotherapies. Behavior, Biology and Chemistry Conference, San Antonio (TX), USA Mar 2016.

2015

Marcos-Contreras Oscar A., Smith Shannon M., Bellinger Dwight A., Merricks Elizabeth, Faella Armida, Pavani Giulia, Zhou Shangzhen, Nichols Timothy C., High Katherine A., Margaritis Paris: Long-term correction of canine FVII deficiency using AAV-mediated expression of zymogen FVII. International Society of Thrombosis and Haemostasis Meeting Jun 2015.

2014

Pavani Giulia, Stafford Katherine, Margaritis Paris: Sequence determinants of mouse Protein C interaction with mouse Endothelial Protein C Receptor. American Society for Hematology Annual Meeting, San Francisco (CA), USA  Dec 2014.

Elkouby Liron, Davidson Robert J., Margaritis Paris, High Katherine A., Sabatino Denise E. : Improved Factor VIII Expression with the Introduction of a PACE-Furin Variant into Codon-Optimized Human Factor VIII. American Society for Hematology Annual Meeting, San Francisco (CA), USA   Dec 2014.

Connolly Courtney T., Faella Armida, Nichols Timothy C., High Katherine A., Arruda Valder R.,  Margaritis Paris: VKORc1 underexpression in skeletal muscle of humans, dogs, and mice: potential implications for ectopic coagulation factor expression in preclinical and therapeutic applications. American Society for Hematology Annual Meeting, San Francisco (CA), USA  Dec 2014.

Pavani Giulia, Stafford Katherine A., Margaritis Paris: Sequence determinants of mouse Protein C interaction with mouse Endothelial Protein C Receptor. 43rd Annual Philadelphia Workshop on Hemostasis, Thrombosis and Atherosclerosis Nov 2014.

Nanaware-Kharade N., Gonzalez III G.A., Reichard E. E., Wolf S., Margaritis P., Peterson E. C.: Using Adeno-Associated Virus (AAV) Mediated Sustained Expression of an Anti-methamphetamine Antibody Fragment to Alter Methamphetamine Disposition in Mice. American Association of Pharmaceutical Scientists Annual Meeting, San Diego (CA), USA Nov 2014.

Pavani Giulia, Ivanciu Lacramioara, Faella Armida, Marcos-Contreras Oscar O., Margaritis Paris: Binding of FVIIa to the endothelial Protein C receptor enhances its hemostatic function in hemophilic mice  Thrombosis and Hemostasis Summit of North America meeting, Chicago (IL), USA Apr 2014.

Posters and Presentations

Posters

Marcos-Contreras Oscar A., Smith Shannon M., Bellinger Dwight A., Merricks Elizabeth, Faella Armida, Pavani Giulia, Zhou Shangzhen, Nichols Timothy C., High Katherine A., Margaritis Paris: Long-term correction of canine FVII deficiency using AAV-mediated expression of zymogen FVII CHOP Research Poster Day Feb 2015.

Connolly Courtney T., Faella Armida, Nichols Timothy C., High Katherine A., Arruda Valder R.,  Margaritis Paris: VKORc1 underexpression in skeletal muscle of humans, dogs, and mice: potential implications for ectopic coagulation factor expression in preclinical and therapeutic applications. CHOP Research Poster Day Feb 2015.

Lectures by Invitation

2016

"Gene based therapeutic approaches for bleeding disorders using coagulation Factor VII", University of Arkansas for Medical Sciences, Little Rock (AR)

2015

"Novel Therapeutic Approaches for Bleeding Disorders: Engineering Factor VII", University of North Carolina at Chapel Hill, Chapel Hill (NC)

2014

"Novel Therapeutic Approaches for bleeding Disorders: Engineering Factor VII" - School in Biochemistry, Molecular Biology and Biotechnology, University of Ferrara, Italy

Awards and Honors

2015, GRIFOLS Martin Villar Haemostasis Award, "The endothelial protein C receptor enhances hemostasis of FVIIa administration in hemophilic mice in vivo" manuscript. First author (Giulia Pavani) award recipient, Paris Margaritis, PI.

1996-1999, Graduate Scholarship, The Alexander S. Onassis Public Benefit Foundation (Greece)

1995,  "John Corran" Book Prize, Department of Genetics, The University of Newcastle-upon-Tyne (UK)

1994, Wellcome Trust summer studentship, Human Molecular Genetics Unit, The University of Newcastle-upon-Tyne (UK)

Editorial and Academic Positions

Editorial Positions

Editorial Board Member

Genetic Disorders and Gene Therapy

Reviewer

Journal of Blood Medicine

Ad-hoc reviewer

2016-present,  Hemophilia
2011-present, PLoS One
2011-present, Journal of Genetic Syndrome and Gene Therapy
2010-present, Journal of Thrombosis and Hemostasis
2010-present, The Veterinary Journal
2009-present, Thrombosis and Haemostasis
2009-present, Thrombosis Research
2008-present, Blood
2008-present, Molecular Therapy

Leadership and Memberships

Memberships in Professional Organizations

International

2009-present, Faculty of 1000 (Medicine) (Associate Member)
2009-present, International Society of Thrombosis and Haemostasis (Member)

National

2015 American Heart Association
- 2015, Grant Reviewer (Basic Cell - Genetics and Epigenetics 3)

2014-present, North American Society of Thrombosis and Hemostasis (Member)

2009-present, American Society of Hematology (Member)

2009-present, American Society of Gene and Cell Therapy (Member)