Rodney M. Camire, Ph.D.

« Back to Members

Associate Professor of Pediatrics
University of Pennsylvania & The Children's Hospital of Philadelphia

Education and Training

Saint Anselm College, B.A, 1994

University of Vermont, Dept. of Biochemistry, Ph.D., 1998

The University of Pennsylvania and The Children's Hospital of Philadelphia, Division of Hematology, Postdoctoral Fellow, 1998-2001

Research Interests

The studies in my laboratory focus on the molecular mechanisms which are responsible for maintaining normal hemostasis. The generation of thrombin at the correct time and place is central to this process as inappropriate production can lead to hemorrhage or thrombosis. Our studies are directed toward understanding how discrete proteolysis of zymogen and procofactor proteins involved in blood coagulation relates to the expression of structural determinants (e.g. exosites, metal binding sites, active site, etc.) important to their function. Procofactors and zymogens cannot participate to any significant degree in their respective macromolecular enzymatic complexes. This indicates that proteolytic activation must result in appropriate structural changes that lead to the expression of sites which impart enzyme, substrate and cofactor binding capabilities.

Specifically, my laboratory is interested in studying the conversion of factor V to factor Va and factor X to factor Xa as model systems to provide insight into the molecular mechanisms underlying the expression of macromolecular binding interactions that accompany transitions from the procofactor and zymogen states. These processes are poorly defined, despite their physiologic importance and new insights into these mechanisms may aid in the development of exosite based FXa or FVa inhibitors capable of attenuating the abnormal hemostatic processes in thrombophilic disease states. Furthermore, information gathered from this work is being used to develop a new class of therapeutic procoagulant bypass agents for the treatment of hemophilia. We are using state of the art techniques to assess clot formation in vivo in murine models of hemophilia A and B.

Publications

Toso, R. and Camire, R.M. Removal of B-domain sequences from factor V rather than specific proteolysis underlies the mechanism by which cofactor function is realized. J. Biol. Chem. 279, 21643-21650, 2004.

Sun, Y.M., Jin, D.Y., Camire, R.M. and Stafford, D.W. Vitamin K epoxide reductase significantly improves carboxylation in a cell line over-expressing factor X. Blood 106, 3811-3815, 2005.

Schlachterman, A., Schuettrumpf, J., Liu, J., Furlan Freguia, C., Toso, R., Poncz, M., Camire, R.M., and Arruda, V.R. Factor V Leiden improves hemostasis in murine hemophilia models. J. Thromb. Haemost. 3, 2730-2737, 2005.

Toso, R. and Camire, R.M. Role of hirudin-like factor Va heavy chain sequences in prothrombinase function. J. Biol. Chem. 281, 8773-8779, 2006.

Zhu, H., Toso, R. and Camire, R.M. Inhibitory sequences within the B-domain stabilize circulating factor V in an inactive state. J. Biol. Chem. 282, 15033-15039, 2007.

Hacisalihoglu, A., Panizzi, P., Bock, P.E., Camire, R.M., and Krishnaswamy, S. Restricted active site docking by enzyme-bound substrate enforces the ordered cleavage of prothrombin by prothrombinase. J. Biol. Chem. 282, 32974-32982, 2007.

Aljamali, M.N., Margaritis, P., Schlachterman, A., Tai, S.J., Roy, E., Bunte, R., Camire, R.M., and High, K.A. Long-term expression of murine factor VIIa is safe but elevated levels result in premature mortality. J. Clin. Invest. 118, 1825-1834, 2008.

Cao, W., Krishnaswamy, S., Camire, R.M., Lenting, P.J., and Zheng, X.L. Factor VIII accelerates proteolytic cleavage of von Willebrand Factor by ADAMTS13. Proc. Natl. Acad. Sci. U.S.A. 105, 7416-7421, 2008.

Toso, R., Zhu, H., and Camire, R.M. The conformational switch from the factor X zymogen to protease state mediates exosite expression and prothrombinase assembly. J. Biol. Chem. 283, 18627-18635, 2008.

Jeimy, S.B., Fuller, N., Tasneem, S., Segers, K., Stafford, A.R., Weitz, J.I., Camire, R.M., Nicolaes, G.A.F., and Hayward, C.P.M. Multimerin 1 binds factor V and activated factor V with high affinity and inhibits thrombin generation. Thromb. Haemost. 100/6, 1058-1067, 2008.

Technologies Available for Licensing

"Enhanced Gamma-Carboxylation of Recombinant Vitamin K-dependent Clotting Factors." Rodney M. Camire, Ph.D., Katherine A. High, M.D., Peter Larson, M.D., and Darrel W. Stafford, Ph.D. U.S. Patent Number 7,220,849. Issued May 22, 2007 (Internal reference: CHOP-0082).

"Compositions and Methods for the Treatment of Hemophilia A." Rodney M. Camire, Ph.D. and Katherine A. High, M.D. U.S. Patent Number 7,211,558 B2 Issued May 1, 2007 (Internal reference: CHOP-0176).

"Gene-based approach for treatment of bleeding disorders using a bypass strategy." Katherine A. High, M.D., Paris Margaritis, Ph.D., and Rodney M. Camire, Ph.D. Patent Pending. Filed March 2001. (Internal reference: CHOP-0105).

"Anticoagulant protein for the treatment or prevention of thrombosis in high-risk patients with inherited or acquired hypercoagulability and method for in vivo study of proteins with short half-lives", Valder R. Arruda, M.D., Ph.D., Joerg Schuettrumpf, M.D., and Rodney M. Camire, Ph.D. Patent Pending, Filed March 2005. (Internal reference: CHOP-0264).

"Compositions and Methods for Modulating Hemostasis." Rodney M. Camire, Ph.D., Patent Pending, Filed November 2005. (Internal reference: CHOP-0267).

"Compositions and Methods for Modulating Hemostasis Using Variant Forms of Activated Factor V." Rodney M. Camire, Ph.D. and Valder R. Arruda, M.D., Ph.D. Patent Pending, Filed March 2006. (Internal reference: CHOP-0303).

"Snake Factor V and Methods and Use Thereof as a Procoagulant." Rodney M. Camire, Ph.D. and Mettine H. A. Bos, Ph.D. Patent Pending, Filed November 2008. (Internal reference: CHOP-0425).

Contact Information

Email: rcamire@mail.med.upenn.edu

Phone: 215-590-9968 (Office), 215-590-3873 (Lab)