Wakefield Lab

Housed in the Conrad Jobst Vascular Research Laboratory, the Wakefield Laboratory, led by Dr. Thomas W. Wakefield, has had a longstanding interest in investigating the connection between inflammation and venous thrombosis (VT). We are particularly interested in proteins known as selectins. A type of cell adhesion molecule, selectins help cells stick to one another and to surfaces in their environment. Selectins become upregulated in VT and, since white blood cells — important players in the inflammatory process — have selectin receptors on their surface, they slow down in the presence of selectins, attach to the inside lining of the vein and move into the vein wall and the growing clot.

The hypothesis that inflammation and thrombosis are related dates back to the 1970s. Our group was among the first to propose such a connection, and we have since made real strides in understanding the basic science and biological mechanisms at work when clots form. Our research is highly collaborative, and we work closely with investigators across the University of Michigan.

Almost one million individuals develop VT each year in the United States. These life-threatening clots can travel to the lungs, causing pulmonary embolism and, unfortunately, VT accounts for about 300,000 deaths annually. Those who survive often develop a condition known as post-thrombotic syndrome, pain and swelling in the extremity after DVT. Currently we treat, and try to prevent, VT with anticoagulants, but this approach raises the risk of bleeding, especially in our older patients. But individuals form clots for different reasons, and yet, when we treat VT, we use the same approach for everyone. The goal of the work in our laboratory is to better understand the specific mechanisms underlying VT so we can identify new therapeutic targets. Ultimately our goal is to take a personalized medicine approach to clot treatment and prevention.

The Wakefield Laboratory uses both pre-clinical and clinical investigations to probe the relationship between inflammation and thrombosis and test novel therapeutic approaches. More specifically, we have found that P- and E-selectin are key players in the process of clot development. When we inhibit these pro-inflammatory proteins in our studies, the clots that form are smaller and more prone to dissolve.

Our laboratory has been a leader in investigating and describing the connection between inflammation and venous thrombosis. Ours was one of the first groups to elucidate the complex role of inflammation in the thrombogenic process, including and more specifically, the role of cell adhesion molecules P- and E-selectin and IL-10, and we have conducted the first-ever small clinical trial of a selectin inhibitor for the treatment of DVT. We are also investigating the use of an E-selectin inhibitor in patients with COVID-19, as these patients have a particularly strong inflammatory response which relates to their increased incidence of thrombosis and their increased risk of mortality. Dr. Wakefield recently received a lifetime achievement award from the International Union of Phlebology for our pioneering work in this field, and the ATVB Special Recognition Award in Thrombosis from the American Heart Association.

The Jobst laboratory has led in the development of novel animal models of VT. Investigators in our group have analyzed many preclinical models of VT to gain a greater understanding of their strengths and weaknesses. This work has led to a national conversation on the best utilization of murine models in VT research as well as the demonstration of a new murine model of recurrent VT and pig model of VT. We also have identified several biomarkers of DVT that, when used together, have high positive and negative predictive values for the diagnosis of VT. These markers can help clinicians diagnose DVT in situations when imaging studies are not feasible.