Cardiovascular disease is the leading cause of death in our society, and the major culprit is a blood clot formed by the unwarranted activation of the clotting cascade. While cardiologists can often restore normal blood flow through by widening the blocked artery and inserting a stent to keep it open, this approach require powerful anti-platelet drugs that can themselves cause hemorrhagic or thrombotic problems.

Research in my laboratory focuses on understanding, at the molecular level, how a class of these drugs --- integrin antagonists --- recognize their target receptor and how that interaction actually alters its structure and function. Our biophysical approach to translational research is designed to hasten the development of a new generation of safer and more effective integrin-targeted therapies.

As Director of the Macromolecular Interactions Core Laboratory, I also strive to make an array of biotechnologies “user-friendly” to my colleagues here at the medical school, at Wake Forest University, and to the wider national and international research community.

Recent publications:

Hantgan, R., Stahle, M., Horita, D.:  Entropy Drives Integrin αIIbβ3:Echistatin Binding Evidence from Surface Plasmon Resonance Spectroscopy.  Biochemistry, in press (2007).

Hantgan, R. R., Stahle, M. C., Connor, J. H., Connor, R. F., Mousa, S. A.:  αIIbβ3 priming and clustering by orally active and intravenous integrin antagonists.  J. Thromb. Haemost., 5:542-50 (2007).

Burton, R. A., Tsurupa, G., Hantgan, R. R., Tjandra, N., Medved, L.:  NMR solution structure, stability, and interaction of the recombinant bovine fibrinogen alphaC-domain fragment.  Biochemistry, 46:8550-8560 (2007).

Guthold, M., Liu, W., Sparks, E. A., Jawerth, L. M., Peng, L., Falvo, M., Superfine, R., Hantgan, R. R., Lord, S. T.:  A comparison of the mechanical and structural properties of fibrin fibers with other protein fibers.  Cell Biochem. Biophys., 49:165-181 (2007).

Liu, W., Jawerth, L. M., Sparks, E. A., Falvo, M. R., Hantgan, R. R., Superfine, R., Lord, S. T., Guthold, M.:  Fibrin fibers have extraordinary extensibility and elasticity.  Science, 313:634 (2006).

Hantgan, R. R., Stahle, M.C., Connor, J. H., Horita, D. A., Rocco, M., McLane, M. A., Yakovlev, S., Medved, L.:  Integrin αIIbβ3: ligand interactions are linked to binding-site remodeling.  Protein Sci., 15:1893-906 (2006).

Levi, N., Hantgan, R. R., Lively, M. O., Carroll, D. L., Prasad, G. L.:  C-60-Fullerenes:  Detection of intracellular photoluminescence and lack of cytotoxic effects.  J. Nanobiotechnology, 4:14 (2006).

Ledford, A. S., Weinberg, R. B., Cook, V. R., Hantgan, R. R., Shelness G. S.: Self-association and lipid binding properties of the lipoprotein initiating domain of apolipoprotein B. J. Biol. Chem., 281:8871-6 (2006).

 Liu, W., Jawerth, L. M., Sparks, E. A., Falvo, M. R., Hantgan, R. R., Superfine, R., Lord, S. T., Guthold, M.:  Fibrin fibers have extraordinary extensibility and elasticity.  Science, 313:634 (2006).

Hantgan, R. R., Stahle, M.C., Connor, J. H., Horita, D. A., Rocco, M., McLane, M. A., Yakovlev, S., Medved, L.:  Integrin αIIbβ3: ligand interactions are linked to binding-site remodeling.  Protein Sci., 15:1893-906 (2006).

O'Flaherty, J.T., Rogers, L.C., Paumi, C.M., Hantgan, R.R., Thomas, L.R., Clay, C.E., High, K., Chen, Y.Q., Willingham, M.C., Smitherman, P.K., Kute, T.E., Rao, A., Cramer, S.D., Morrow, C.S.:  5-oxo-ETE analogs and the proliferation of cancer cells. Biochim. Biophys. Acta. 1736:228-236 (2005).

Jerome, W.G., Handt, S., Hantgan, R.R.: Endothelial cells organize fibrin clots into structures that are more resistant to lysis. Microsc. Microanal. 11:268-77 (2005).

Hantgan, R.R., Stahle, M.C., Connor, J.H., Lyles, D.S., Horita, D.A., Rocco, M., Nagaswami, C., Weisel, J.W., McLane, M.A.:  The disintegrin echistatin stabilizes integrin alphaIIbbeta3's open conformation and promotes its oligomerization.  J. Mol. Biol. 342:1625-1636 (2004).

Hantgan, R.R., Gibbs, W., Stahle, M.C., Aster, R.H., Peterson, J.A.:  Integrin clustering mechanisms explored with a soluable αIIbβ3 ectodomain construct.  Biochim. Biophys. Acta., 1700:19-25 (2004).

Guthold, M., Liu, W., Stephens, B., Lord, S.T., Hantgan, R.R., Erie, D.A., Taylor, R.M. Jr., Superfine, R.:  Visualization and Mechanical Manipulations of Individual Fibrin Fibers Suggest that Fiber Cross Section Has Fractal Dimension 1.3.  Biophys. J. 87:4226-42236 (2004).

Chen, K., Ballas, S. K., Hantgan, R.R., Kim-Shapiro, D.B.:  Aggregation of normal and sickle hemoglobin in high concentration phosphate buffer.  Biophys. J. 87:4113-4121 (2004).

Tsurupa, G., Veklich, Y., Hantgan, R., Belkin, A. M., Weisel, J. W., Medved, L.:  Do the isolated fibrinogen αC-domains form ordered oligomers?  Biophys. Chem. 112:257-266 (2004).

Hantgan, R.R., Lyles, D.S., Mallett, T.C., Rocco, M.:  Ligand binding promotes the entropy-driven oligomerization of integrin αIIbβ3.  J. Biol. Chem., 278:3417-3426 (2003).

Mizel, S.B., West, A.P., Hantgan, R.R.:  Identification of a sequence in human toll-like receptor 5 required for the binding of Gram-negative flagellin.  J. Biol. Chem., 278:23624-23629 (2003).

Hantgan, R.R., Stahle, M.C., Jerome, W.G., Nagaswami, C., Weisel, J.W.: Tirofiban blocks platelet adhesion to fibrin with minimal perturbation of GpIIb/IIIa structure.  Thromb. Haemost. 87: 910-917 (2002).

Yamamoto, Y., Poole, L.B., Hantgan, R.R., Kamio, Y.:  An iron-binding protein, Dpr, from Streptococcus mutans prevents iron-dependent hydroxyl radical formation in vitro.  J. Bacteriol. 184: 2931-2939 (2002).

Wood, Z.A., Poole, L.B., Hantgan, R.R., Karplus, P.A.: Dimers to doughnuts: redox-sensitive oligomerization of 2-cysteine peroxiredoxins.  Biochemistry 41: 5493-504 (2002).

Hockey, K. J., Anderson, R. A., Cook, V. R., Hantgan, R. R., Weinberg, R. B.:  The effect of the apolipoprotein A-IV Q360H polymorphism on post-prandial plasma triglyceride clearance.  J. Lipid Res. 42:211-217 (2001).

Patel, V. B., Cunningham, C. C., and Hantgan, R. R.:  Physiochemical properties of rat liver mitochondrial ribosomes.  J. Biol. Chem. 276: 6739-6746 (2001).

Bonnefoy, A., Hantgan, R., Legrand, C., and Frojmovic, M. M.:  A model of platelet aggregation involving multiple interactions of Thrombospondin-1, Fibrinogen and GPIIbIIIa receptor.  J. Biol. Chem. 276: 5605-5612 (2001).

Hantgan, R.R., Stahle, M., Del Gaizo, V., Adams, M., Lasher, T., Jerome, W.G., McKenzie, M., Lyles D.S.:  αIIb's cytoplasmic domain is not required for ligand-induced clustering of integrin aIIbβ3.  Biochim. Biophys. Acta. 1540: 82-95 (2001).

Hantgan, R.R., Rocco, M., Nagaswami, C., Weisel, J.W.:  Binding of a fibrinogen mimetic stabilizes integrin αIIbβ3's open conformation.  Protein Sci. 10: 1614-26 (2001).

Lounes, K.C., Lefkowitz, J.B., Henschen-Edman, A.H., Coates, A.I., Hantgan, R.R., Lord, S.T.:  The impaired polymerization of fibrinogen Longmont (Bβ166Arg-->Cys) is not improved by removal of disulfide-linked dimers from a mixture of dimers and cysteine-linked monomers.  Blood 98: 661-6 (2001).

Lounes, K.C., Lefkowitz, J.B., Coates, A.I., Hantgan, R.R., Henschen-Edman, A., Lord, S.T.:  Fibrinogen Longmont. A heterozygous abnormal fibrinogen with B β Arg-166 to Cys substitution associated with defective fibrin polymerization. Ann. N. Y. Acad. Sci. 936: 129-32 (2001).

Huang, T.C., Jordan, R.E., Hantgan, R.R., Alevriadou, B.R.:  Differential effects of c7E3 Fab on thrombus formation and rt-PA-Mediated thrombolysis under flow conditions. Thromb. Res. 102: 411-25 (2001).

Hogan K.A., Gorkun O.V., Lounes K.C., Coates A.I., Weisel J.W., Hantgan R.R., Lord S.T.  Recombinant fibrinogen Vlissingen/Frankfurt IV.  The deletion of residues 319 and 320 from the gamma chain of fibrinogen alters calcium binding, fibrin polymerization, cross-linking, and platelet aggregation.  J Biol Chem 275:17779-17785 (2000).

Modeling integrin antagonists binding to their target aIIbb3 receptor. From Hantgan et al., Journal of Thrombosis and Haemostasis, 5: 542-550 (2007).