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Molecular Genetics and Genomics Program at Wake Forest University School of Medicine

Roy R. Hantgan
Associate Professor of Biochemistry 

B.S., 1968 Juniata College 
Ph.D., 1974 Cornell University 

 

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. Fortunately, "clot busting" drugs can usually activate the body's natural fibrinolytic system and dissolve the fibrin scaffold of this life-threatening thrombus. However, clots that are rich in platelets are resistant to this thrombolytic therapy. The goal of my research program is to understand the molecular and cellular events that contribute to thrombolytic resistance. 

In my laboratory, we approach the problem from two different perspectives, one focusing on platelet biochemistry and the other on protein structure/function. Our cellular studies use an in vitro model of the lytic-resistant platelet-rich thrombus coupled with a battery of spectroscopic and electron microscopic probes to identify new targets for improved thrombolytic therapy. Our molecular studies focus on the integrin receptors that link the fibrin strands of the blood clot tightly to the platelet surface. The goal of that project is to characterize the solution conformation, aggregation state, and receptor: ligand interactions of the platelet integrin alphallbbeta3 using the tools of solution biophysical chemistry. 


Recent Publications (selected):

Hantgan RR, Stahle M, Del Gaizo V, Adams M, Lasher T, Jerome WG, McKenzie M, Lyles DS. AlphaIIb's cytoplasmic domain is not required for ligand-induced clustering of integrin alphaIIbbeta3. Biochim Biophys Acta. 2001 Jul 25;1540(1):82-95.

Hantgan RR, Rocco M, Nagaswami C, Weisel JW. Binding of a fibrinogen mimetic stabilizes integrin alphaIIbbeta3's open conformation. Protein Sci. 2001 Aug;10(8):1614-26.

Lounes KC, Lefkowitz JB, Henschen-Edman AH, Coates AI, Hantgan RR, Lord ST. The impaired polymerization of fibrinogen Longmont (Bbeta166Arg-->Cys) is not improved by removal of disulfide-linked dimers from a mixture of dimers and cysteine-linked monomers. Blood. 2001 Aug 1;98(3):661-6.

Lounes KC, Lefkowitz JB, Coates AI, Hantgan RR, Henschen-Edman A, Lord ST. Fibrinogen Longmont. A heterozygous abnormal fibrinogen with B beta Arg-166 to Cys substitution associated with defective fibrin polymerization. Ann N Y Acad Sci. 2001;936:129-32.

Huang TC, Jordan RE, Hantgan RR, Alevriadou BR. Differential Effects of c7E3 Fab on Thrombus Formation and rt-PA-Mediated Thrombolysis Under Flow Conditions. Thromb Res. 2001 Jun 1;102(5):411-25.

Hockey KJ, Anderson RA, Cook VR, Hantgan RR, Weinberg RB. Effect of the apolipoprotein A-IV Q360H polymorphism on postprandial plasma triglyceride clearance. J Lipid Res. 2001 Feb;42(2):211-7.

Patel VB, Cunningham CC, Hantgan RR. Physiochemical properties of rat liver mitochondrial ribosomes. J Biol Chem. 2001 Mar 2;276(9):6739-46.

Bonnefoy A, Hantgan R, Legrand C, Frojmovic MM. A model of platelet aggregation involving multiple interactions of thrombospondin-1, fibrinogen, and GPIIbIIIa receptor. J Biol Chem. 2001 Feb 23;276(8):5605-12.

Hogan KA, Gorkun OV, Lounes KC, Coates AI, Weisel JW, Hantgan RR, Lord ST. Recombinant fibrinogen Vlissingen/Frankfurt IV. The deletion of residues 319 and 320 from the gamma chain of firbinogen alters calcium binding, fibrin polymerization, cross-linking, and platelet aggregation. J Biol Chem. 2000 Jun 9;275(23):17778-85.

Hantgan RR, Paumi C, Rocco M, Weisel JW. Effects of ligand-mimetic peptides Arg-Gly-Asp-X (X = Phe, Trp, Ser) on alphaIIbbeta3 integrin conformation and oligomerization. Biochemistry. 1999 Nov 2;38(44):14461-74.

Thomas MJ, Pang K, Chen Q, Lyles D, Hantgan R, Waite M. Lipid exchange between mixed micelles of phospholipid and triton X-100. Biochim Biophys Acta. 1999 Feb 4;1417(1):144-56.