What is fibrinogen?
In our opinion, it is the most important protein involved in blood coagulation. For anyone who has ever had to memorize or even glance at the cascade of proteins involved in blood clotting, you may recall the final step of the process: thrombin cleaves fibrinogen to produce fibrin. The individual fibrin molecules, or monomers, spontaneously polymerize in an ordered fashion to produce an intricate network of fibers. These fibers are the structural backbone of a thrombus, in which red blood cells and platelets can help to plug the wound at the site of injury.

What does our lab do?
The specialty of our lab is our ability to synthesize recombinant fibrinogens in Chinese Hamster Ovary (CHO) cells. Although we produce normal recombinant fibrinogen, we are most interested in synthesizing and studying specific recombinant variants.  The major purpose of creating these variants is to examine the residues important for interactions within a molecule and also with other molecules.

How do we decide which variants to make?
There are two ways in which we choose the mutations we will make. First, we choose to alter amino acids that have been implicated to have a distinct role in one of fibrinogen’s many functions, such as polymerization. With these variant fibrinogens, we are able to explore the structure-function relationship of fibrinogen.  Alternatively, we may model a mutation after a specific clinical case study. Natural variations in fibrinogen are termed dysfibrinogens, and often these variations can have devastating effects on a person’s well-being. For example, some dysfibrinogens can cause a bleeding disease, while others can cause thrombosis. Most dysfibrinogens occur in the heterozygous form, so by creating a homogeneous population of the variant fibrinogens, we can directly study the effect of the mutation. 

What do we do with the recombinant fibrinogen?
Some of us in the lab are very interested in the biochemistry of the molecule. By studying how the variant recombinant fibrinogens differ from normal fibrinogen under many conditions, we learn much about the structure and essential, functional domains of fibrinogen. Each fibrinogen molecule is a dimer made of six polypeptide chains (2Aa, 2Bb, and 2g).
 
Some of the ways in which we compare our proteins are by performing in vitro experiments which correlate to some aspect of an in vivo function of fibrinogen. For example, some of the functions we study are:

Fibrinogen Structure by X-Ray Crystallography
How fibrinogen bridges platelets during platelet aggregation
The kinetic process of polymerization
Final fiber thickness
Factor XIII cross-linking
Fibrinopeptide release
Calcium binding to fibrinogen
Clot lysis and plasmin degradation of fibrin
Clot retraction
Platelet signalling

Besides recombinant proteins, what else do we study in the lab?
Some of us in the lab are more interested in how fibrinogen contributes to a disease process such as atherosclerosis or thrombophilia. To investigate fibrinogen’s role in these two diseases, we are interested in studying mouse models. For example, Alyssa Gulledge, a former graduate student in the lab, constructed a mouse that overexpresses fibinogen. She looked at these mice to determine if overexpression of fibrinogen is a cause or effect of atherosclerosis.  We have also succeeded in making a mouse model of thrombophilia by producing a mouse with the Vlissingen/Frankfurt IV mutation.