Institute for Translational Medicine and Therapeutics || University of Pennsylvania

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Vladimir R. Muzykantov, M.D., Ph.D.
Associate Professor of Pharmacology and Medicine

Director, Targeted Therapeutics Program, ITMAT
Senior Investigator, Institute for Environmental Medicine

Member, Graduate Group in Pharmacological Sciences
Member, Bioengineering Graduate Group

Institute for Translational Medicine and Therapeutics
814 Biomedical Research Building II/III
University of Pennsylvania
421 Curie Boulevard
Philadelphia, PA 19104-6160

Telephone: 215-898-0254
Fax: 215-573-9004
Email: muzykant@mail.med.upenn.edu

Education:
1980	M.D. (Internal Medicine)	Moscow Medical School
1985	Ph.D. (Biochemistry)	Russian Cardiology Research Center

Research Summary:
Dr. Muzykantov works in the field of drug targeting. His research interests are focused in the areas of vascular targeting of enzyme therapeutics for containment of oxidative and thrombotic vascular stress, inflammation, endothelial injury and ischemia-reperfusion. The more new, powerful therapeutic agents are designed, the higher is interest in two questions: i) how to minimize their side effects via a more adequate delivery to therapeutic targets - an affected organ, tissue or cell; and, ii) how to improve their effects by precise addressing into the desirable subcellular compartments. For example, many enzymes and other therapeutic proteins are available in purified or recombinant forms and could find therapeutic use, but their sub-optimal delivery to therapeutic targets restricts therapeutic effects and cause side effects.

Muzykantov explores two strategies for delivery of anti-thrombotic enzymes: carriage by red blood cells and immunotargeting to endothelial surface determinants using recombinant fusion protein constructs. He also designs strategies for intracellular immunotargeting of drugs into endothelial cells using vehicles including immunoconjugates and polymer nanocarriers directed to cell adhesion molecules. This research includes studies of: i) Role of carriers geometry (size and shape) and endothelial environment, flow and functional status in targeting and endothelial responses to targeting; ii) The mechanisms of sub-cellular and trans-cellular addressing of targeted cargoes; and, iii) Pharmacokinetics, therapeutic and potential side effects in animals. Methodology includes protein biochemistry, bioconjugation and bioengineering; design of polymer carriers for drug delivery, morphological and imaging techniques, nano-technologies, recombinant, cell and molecular biology techniques; animal studies. The goal of this research supported by several grants from NIH, American Heart Association, Department of Defense, Pennsylvania Nano-Technology Institute, and the Penn Research Foundation is better understanding of action and optimization of design of drug delivery strategies and translation into the clinical domain.

Selected Key Publications:
Muzykantov V, Atochina E, Ischiropoulos H, Danilov S & Fisher A: Immunotargeting of antioxidant enzymes to the pulmonary endothelium. Proc Natl Acad Sci USA 93: 5213-5218, 1996.

Muzykantov V, Christofidou M, Balyasnikova I, Harshaw D, Schultz L, Fisher A & Albelda S: Streptavidin facilitates internalization and pulmonary targeting of an anti-endothelial cell antibody (PECAM): a strategy for intraendothelial drug delivery. Proc Natl Acad Sci USA 96: 2379-2384, 1999.

Scherpereel A, Wiewrodt R, Christofidou-Solomidou M, Gervais R, Murciano J-C, Albelda SM & Muzykantov VR: Cell-selective intracellular delivery of a foreign enzyme to endothelium in vivo using vascular immunotargeting FASEB J 15:416-426, 2001.

Wiewrodt R, Thomas A, Cipelletti L, Christofidou-Solomidou M, Weitz D, Feinstein SI, Schaffer D, Albelda SM, Koval M & Muzykantov V: Size-dependent immunotargeting of cargo materials into endothelial cells. Blood 99: 912-922, 2002.

Muro S, Wiewrodt R, Thomas A, Koniaris L, Albelda S, Muzykantov V & Koval M: A novel endocytic pathway induced by clustering endothelial ICAM-1 or PECAM-1. J Cell Sci 116: 1599-1609, 2003.

Kozower B, Christofidou-Solomidou M, Sweitzer T, Muro S, Buerk D, Solomides C, Albelda A, Patterson G & Muzykantov V: Immunotargeting of catalase to the pulmonary endothelium alleviates oxidative stress and reduces acute transplantation lung injury. Nature Biotech 21: 392-398, 2003.

Murciano JC, Medinilla S, Eslin D, Atochina E, Cines DB & Muzykantov VR: Prophylactic fibrinolysis through selective dissolution of nascent clots by tPA-carrying erythrocytes. Nature Biotech 21: 891-896, 2003.

Atochin D, Murciano JC, Cursoy-Ozdemir Y, Krasik T, Noda F, Ayata C, Dunn A, Moskowitz M, Huang P & Muzykantov VR: Mouse model of microembolic stroke and reperfusion. Stroke 35: 2177-2182, 2004.

Muro S, Gayewsky C, Koval M & Muzykantov V: ICAM-1 recycling in endothelial cells: a novel pathway for sustained intracellular delivery and prolonged effects of drugs. Blood 105: 650-658, 2005.

Dziubla TD, Karim A & Muzykantov V: Polymer nanocarriers protecting active enzyme cargo against proteolysis. J Contr Rel 102: 427-439, 2005.

Awards, Honors, Membership in Honorary Societies:

•	USSR National Young Investigator Award in Pharmacology, 1st Prize (1986)
•	Young Investigator Award, The World Congress of Angiology, Rome (1989)
•	Young Investigator Award, 16th LH Gray Conference on Tumor Vasculature, Manchester (1990)
•	International Union of Biochemistry Wood Award, Visiting Scientist, Department of Biochemistry, University of Virginia (1992)
•	International Society of Immunology Travel Award, 8th International Congress of Immunology, Budapest (1992)
•	AHA Established Investigator (1997)
•	The Pulmonary Circulation Assembly Highlight of American Thoracic Society International Scientific Conference: “Intracellular immunotargeting of active reporter enzyme to endothelium in vivo” (2000)
•	First Prize of the German Society of Pulmonary Medicine Pulmedica-Preis (2000)
•	Bugher Stroke Award, National American Heart Association (2001)
•	National AHA plaque “In recognition of outstanding efforts in research fighting the heart disease and stroke” (2001)
•	Keynote Speaker, 4th Annual Colloqium “Cellular and Molecular Biomechanics”, University of Virginia, Charlottesville, VA (2003)

Laboratory Personnel:

Dr. Kristina Danielyan Postdoctoral Fellow danielya@pobox.upenn.edu	Dr. Tom Dziubla Research Associate dziubla@mail.med.upenn.edu
Mr. Bisen Ding Graduate Student ding2@mail.med.upenn.edu	Dr. Kumkum Ganguly Postdoctoral Fellow kumkum@mail.med.upenn.edu
Dr. Carmen Garnacho Postdoctoral Fellow carmengm@mail.med.upenn.edu	Mr. John Leferovich Research Specialist jleferov@mail.med.upenn.edu
Dr. Silvia Muro Res. Assistant Prof. silvia@mail.med.upenn.edu	Ms. Weining Qui Graduate Student weiningq@seas.upenn.edu
Mr. Eric Simone Graduate Student esimone@seas.upenn.edu	Dr. Vladimir Shuvaev Res. Investigator shuvaevv@mail.med.upenn.edu
Dr. Thomas Stover Postdoctoral Fellow tstover@mail.med.upenn.edu	Mrs. Samira Tilba Research Specialist stilba@mail.med.upenn.edu
Dr. Sergei Zaitzev Research Associate zaitzev@mail.med.upenn.edu

Lab Address:
Institute for Translational Medicine and Therapeutics
823 Biomedical Research Building II/III
University of Pennsylvania
421 Curie Blvd.
Philadelphia, PA 19104-6160

Lab Telephone: 215-746-2337 Lab Fax: 215-573-9004

IFEM Lab Address:
One John Morgan Building
University of Pennsylvania School of Medicine
3620 Hamilton Walk
Philadelphia PA 19104-6068

Telephone: 215-898-9823 Fax: 215-898-0868

Institute for Translational Medicine and Therapeutics || University of Pennsylvania