The theme has long been the molecular identification, pathways and structural biology of the molecules constituting the pathogenetic mechanisms of major diseases particularly those that involve vascular biology. Following competitive identification, cloning and establishment of functional pathways of the blood coagulation system we identified various disease associated lipoproteins, then addressed application of these and other molecular pathways and functions to therapeutic design. Major advances are being realized in detailed elucidation the coagulation, aka thrombogenic, molecular cascades and the discovery of precise selective molecular interventions based on the structural biology of the involved precise structural interactions of proteins. Going beyond attenuation of thrombotic disease, the molecular insight has been advanced to therapeutic thrombosis of solid tumors for infarctive eradication. Analysis of in vivo gene display by the vasculature of solid tumors has led to new insight and targets for safe and effective cancer therapy. Lead therapeutic compounds have been designed, patented and advancing to clinical trials. We continue to focus on search and discovery science to advance knowledge and solutions based on the molecular maps of pathogenetic processes.
EL-Sheikh, A., Liu, C., Huang, H., and Edgington, T.S. A novel vascular endothelial growth factor heparin-binding domain substructure binds to glycosaminoglycans in vivo, and localizes to tumor microvascular endothelium. Cancer Res. 62(23):7118-7123, 2002.
Liu, C., Sun, C., Huang, H., Janda, K., and Edgington, T. Over-expression of legumain in tumors is significant for invasion/metastasis and a candidate enzymatic target for prodrug therapy. Cancer Res. 63:2957-2964, 2003.
Huang, H., Norledge, B.V., Liu, C., Olson, A.J., and Edgington, T.S. Selective attenuation of the extrinsic limb of the tissue factor driven coagulation protease cascade by occupancy of a novel peptidyl docking site on tissue factor. Biochemistry 42(36):10619-26, 2003.
Liu, C., Dickinson, C., Shobe, J., DoZate, F., Ruf, W., and Edgington, T.S. A hybrid fibronectin motif protein as an integrin targeting selective tumor vascular thrombogen. Mol. Cancer Therap.3:793-801, 2004
Edgington, T.S., Glassock, R.J., and Dixon, F.J. Autologous immune-complex pathogenesis of experimental allergic glomerulonephritis. Science 155:1432-1434, 1967.
Edgington, T.S., and Ritt, D.J. Intrahepatic expression of serum hepatitis virus-associated antigens. J. Exp. Med. 134:871-885, 1971.
Morrissey, J.H., Fakhrai, H., and Edgington, T.S. Molecular cloning of the cDNA for tissue factor, the cellular receptor for the initiation of the coagulation protease cascade. Cell 50:129-135, 1987.
Drake, T.A., Morrissey, J.H., and Edgington, T.S. Selective cellular expression of tissue factor in human tissues: Implications for disorders of hemostasis and thrombosis. Am. J. Pathol. 134:1087-1097, 1989.
Lathey, J.L., Agosti, J.M., Nelson, J.A., Corey, L., Gregory, S.A., Morrissey, J.H., Edgington, T.S., and Oldstone, M.B.A. A selective defect in tissue factor mRNA expression in monocytes from AIDS patients. Clin. Immunol. Immunopathol. 54:1â€‘13, 1990.
Taylor, F.B., Jr., Chang, A.K., Ruf, W., Morrissey, J.H., Hinshaw, L.B., Catlett, R., Blick, K., and Edgington, T.S. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibodies. Circ. Shock 33:127-134, 1991.
Mackman, N., Fowler, B.J., Edgington, T.S., and Morrissey, J.H. Functional analysis of the human tissue factor promoter and induction by serum. Proc. Natl. Acad. Sci. USA, 87:2254-2258, 1990.
Ruf, W., and Edgington, T.S. An anti-tissue factor monoclonal antibody which inhibits [TF:VIIa] complex is a potent anticoagulant in plasma. Thromb. Haemost. 66:529-533, 1991.
Huang, X., Molema, G., King, S., Watkins, L., Edgington, T.S., and Thorpe, P.E. Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor vasculature. Science 275:547-550, 1997.
Liu, C., Huang, H., Doñate, F., Dickinson, C., Santucci, R., EL-Sheikh, A., Vessella, R., and Edgington, T.S. Prostate-specific membrane antigen directed selective thrombotic infarction of tumors. Cancer Res. 62(19):5470-5475, 2002.
Lin, R., Maeda, S., Liu, C., Karin, M., Edgington, T.S. A large non-coding RNA is a marker for murine and human hepatocellular carcinomas. Oncogene, 26:851-858, 2007.
Mackman, N., Morrissey, J.H., Fowler, B., and Edgington, T.S. Complete sequence of the human tissue factor gene, a highly regulated cellular receptor that initiates the coagulation protease cascade. Biochemistry 28:1755-1762, 1989.