Susan T. Lord Ph.D.

Department of Pathology and Lab Medicine

Department of Chemistry

Department of Genetics

Contact Info: Office: 919-966-3584, Lab: 919-966-2617, Email: stl@med.unc.edu

I am the PI. I received my Ph.D. in Biochemistry from Cornell University Medical College. I was a postdoc at Yale University where I worked with Ca++ ATPase in muscle sarcoplasmic reticulum. I was then a staff fellow at the National Cancer Institute at Bethesda, Maryland where I worked with the SV40 DNA tumor virus. Since 1982, I have been at the University of North Carolina, where I began our studies with fibrinogen.

I am a Professor of Pathology and Lab Medicine, and an Adjunct Professor of Chemistry. I am also a member of the Curriculum of Genetics and Molecular Biology and the Carolina Cardiovascular Biology Center.

Our research is focused on the coagulation protein fibrinogen. Fibrinogen contributes structure and strength to a blood clot and thus has a central role in both hemostasis and thrombosis. Fibrinogen also interacts with many different cell types to mediate critical processes such as clot retraction, wound healing and vascular remodeling. Our studies offer insight into the molecular mechanisms that mediate fibrinogens functions with the long term goal of providing basic information relevant to the prevention or treatment of disease. Most of our past studies fit into two general categories—1) biochemical studies using pure recombinant fibrinogen to examine the molecular mechanisms of clot formation and dissolution and 2) in vivo studies using mouse models and patient samples to examine the role of fibrinogen in cardiovascular disease. These studies are supported by the National Institutes of Health and the American Heart Association.

We also have collaborations in two areas--the adsorption of fibrinogen to surfaces and the mechanical properties of fibrinogen and fibrin fibers. The former studies are in collaboration with Mark Schoenfisch, an analytical chemist whose laboratory examines the biocompatibility of medical implants and sensors. The latter studies are done in collaboration with Rich Superfine and Mike Falvo, physicists at UNC-Chapel Hill, and Martin Guthold, a physicist at Wake Forest University. In these studies we measure the forces needed to stretch and break individual fibrin fibers. Our first results were published in Science in August 2006. We have funding from the National Science Foundation to support further studies of these remarkable physical properties.

References:

Fibrinogen and fibrin: scaffold proteins in hemostasis. Lord ST, Curr Opin Hematol 14:236-241, 2007.

Probing the g2 Calcium-Binding Site: Studies with gD298,301A Fibrinogen Reveal Changes in the g294-301 Loop that Alter the Integrity of the "a" Polymerization Site. Kostelansky MS, Lounes KC, Ping LF, Dickerson SK, Gorkun OV, and Lord ST, Biochemistry 46:5114-23, 2007.

Fibrin fibers have extraordinary extensibility and elasticity. Liu W, Jawerth LM, Sparks EA, Falvo MR, Hantgan RR, Superfine R, **Lord ST and **Guthold M, (**corresponding authors) Science 313:634, 2006.

The structure of fibrinogen fragment D with the “A” knob peptide GPRVVE. Betts L, Merenbloom BK, and Lord ST, J Thromb Haemost 4:1139-41, 2006.

Interactions of thrombin with fibrinogen adsorbed on methyl-, hydroxyl-, amine-, and carboxyl-terminated self-assembled monolayers. Evans-Nguyen KM, Tolles LR, Gorkun OV, Lord ST, and Schoenfisch MH, Biochemistry 44:15561-8, 2005

The aC domains of fibrinogen affect the structure of the fibrin clot, its physical properties, and its susceptibility to fibrinolysis. Collet JP, Moen JL, Veklich YI, Gorkun OV, Lord ST, Montalescot G, and Weisel JW, Blood 106:3824-30, 2005.

Neonatal bleeding and decreased plasma fibrinogen levels in mice modeled after the dysfibrinogen Vlissingen/Frankfurt IV. Hogan KA, Merenbloom BK, Kim HS and Lord ST, J Thromb Haemost. 2:1484-7, 2004.

Calcium-binding site b2, adjacent to the "b" polymerization site, modulates lateral aggregation of protofibrils during fibrin polymerization. Kostelansky MS, Lounes KC, Ping LF, Dickerson SK, Gorkun OV, and Lord ST, Biochemistry 43:2475-83, 2004.

Cause-effect relation between hyperfibrinogenemia and vascular disease. Kerlin BA, Cooley BC, Isermann BH, Hernandez I, Sood R, Zogg M, Hendrickson SB, Mosesson MW, Lord S, and Weiler H, Blood 103:1728-34, 2004.

Effects of hyperfibrinogenemia on vasculature of C57BL/6 mice with and without atherogenic diet. Gulledge AA, McShea C, Schwartz T, Koch G, and Lord ST, Arterioscler Thromb Vasc Biol. 23:130-135, 2003.

Analysis of engineered fibrinogen variants suggests that an additional site mediates platelet aggregation and that “B-b” interactions have a role in protofibril formation. Lounes KC, Ping LF, Gorkun OV, and Lord ST, Biochemistry 41:5291-9, 2002.

Mouse models in coagulation. Hogan KA, Weiler H, and Lord ST, Review Article, Thromb Haemost 87:563-74, 2002.

A novel transgenic mouse model of hyperfibrinogenemia. Gulledge AA, Rezaee F, Verheijen JH and Lord ST, Thromb Haemost 86:511-16, 2001.