Vladimir R. Muzykantov, M.D., Ph.D.
Associate Professor of Pharmacology and
Medicine
Director, Targeted Therapeutics Program,
ITMAT
Senior Investigator, Institute for Environmental
Medicine
Chair, Graduate Group in Pharmacological
Sciences
Member, Bioengineering Graduate Group
ITMAT Lab: R823 BRBII/III
Telephone: 215-746-2337
IFEM Lab and office
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
Email: muzykant@mail.med.upenn.edu
Link: http://www.itmat.upenn.edu
Department of Pharmacology
Vladimir R. Muzykantov, M.D., Ph.D.
Education:| 1980 | M.D. (Internal Medicine) | Moscow Medical School |
| 1985 | Ph.D. (Biochemistry) |
Russian Cardiology Research Center |
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 grants from NIH and the Penn Research Foundation, is better understanding of action and optimization of design of drug delivery strategies and translation into the clinical domain.
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.
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 (Journal cover).
Muro S, Gayewsky C, Koval M and 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 and Muzykantov V: Polymer nanocarriers protecting active enzyme cargo against proteolysis. J Contr Rel 102: 427-439, 2005.
Ganguly K, Krasik T, Medinilla S, Bdeir K, Cines D, Muzykantov V and Murciano J-C: Blood clearance and activity of erythrocyte-coupled fibrinolytics. J Pharm Exp Therap 312: 1106-1113, 2005.
Ding B-S, Gottstein C, Grunow A, Kuo A, Ganguly K, Albelda S, Cines D and Muzykantov VR: Endothelial targeting of a recombinant construct fusing a PECAM-1 single-chain variable antibody fragment (scFv) with pro-urokinase facilitates prophylactic thrombolysis in the pulmonary vasculature. Blood 106: 4191-4198, 2005.
Muro S, Matescu M, Gayewsky C, Muzykantov V and Koval M: Control of intracellular trafficking of ICAM-1 targeted nanocarriers by endothelial Na/N exchanger (NHE) proteins. Am J Physiol Lung Cell Mol Physiol 290: L809-817 (Editorial Highlight), 2006.
Muro S, Dziubla T, Qui W, Leferovich J, Cui X, Berk E and Muzykantov VR: Endothelial targeting of high-affinity multivalent polymer nanocarriers directed to ICAM-1. J Pharm Exp Therap 317: 1161-1169, 2006.
Zaitsev S, Danielyan K, Murciano JC, Krasik T, Taylor RP, Pincus S, Jones SM, Cines DB, Muzykantov VR: (2006) CR1-directed targeting of tPA to circulating erythrocytes for prophylactic fibrinolysis. Blood 108: 1895-1902 (Editorial Highlight), 2006.
Ganguly K, Murciano JC, Westrick R, Leferovich J, Cines D and Muzykantov VR: (2007) The glycocalyx protects erythrocyte-bound tissue type plasminogen activator from enzymatic inhibition. J Pharm Exp Therap 321: 158-164, 2007.
Danielyan K, Ding B, Gottstein C, Cines D and Muzykantov VR: Delivery of anti-PECAM scFv-urokinase fusion protein to the cerebreal vasculature lyses arterial clots and attenuates post-ischemic brain edema. J Pharm Exp Therap 321: 947-952 (Journal Cover), 2007.
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) |
| • | First Prize of the German Society of Pulmonary Medicine (Pulmedica-Preis) (2000) |
| • | Bugher Stroke Award, National American Heart Association (2001) |
| • | American Heart Association plaque "In recognition of outstanding efforts in research fighting the heart disease and stroke" (2001) |
| • | Keynote Speaker, 4th Annual Colloquium "Cellular and Molecular Biomechanics", University of Virginia, Charlottesville, VA (2003) |
| • | Keynote Speaker, International Graduate Course in Drug Delivery, University of Groningem, The Netherlands (2005) |
| Mr. Bisen Ding Graduate Student ding2@mail.med.upenn.edu |
Dr. Marc Ilyes Post-doctoral fellow iliesma@sas.upenn.edu |
| Dr. Vladimir Shuvaev Research Investigator shuvaevv@mail.med.upenn.edu |
Mr. Eric Simone Graduate Student esimone@seas.upenn.edu |
| Dr. Sergei Zaitzev Research Assistant Professor zaitzev@mail.med.upenn.edu |
Institute for Translational Medicine and Therapeutics
823 Biomedical Research Building II/III
University of Pennsylvania School of Medicine
421 Curie Blvd.
Philadelphia PA 19104-6160
Lab Telephone: 215-746-2337 Lab Fax: 215-573-9004 Link: http://www.itmat.upenn.edu