Our research focuses on using markers that can be found in the blood or other bodily fluids, known as biomarkers, to predict a patient’s risk for a disease, potential outcome from a treatment or intervention, or to help guide a patient’s treatment plan.
Our current lab favorite biomarker is soluble urokinase plasminogen activator receptor (suPAR), which is known to be elevated in our blood with inflammation – our body’s response to injury or illness - but not with acute stress episodes (such as surgery or heart attacks.) It is also known to be elevated with common risk factors, like increased age, smoking, diabetes, or autoimmune diseases. These qualities make suPAR superior to current biomarkers, and a great marker to look at as an easy, inexpensive, standalone test for disorders such as heart disease or kidney disease. While we look at the connections between these diseases, and expand into other diseases and conditions, we hope to be able to use this test to provide individualized therapies for patients with various conditions.
suPAR, a predictive biomarker
The urokinase receptor system is a key regulator of the intersection between inflammation, immunity and coagulation, and suPAR is the circulating form of a glycosyl-phosphatidylinositol-anchored three-domain membrane (DI, DII, and DIII) protein expressed on a variety of cells including immunologically active cells, endothelial cells and podocytes. The membrane bound form (uPAR) is involved in the regulation of cell adhesion and migration, specifically of immune cells. This is achieved through binding of integrins, enabling uPAR-expressing cells to move through the extracellular matrix.
While the specific physiologic role of the soluble form is unclear, suPAR is known to be a biomarker of the innate arm of the immune system, and suPAR levels in circulation are thought to reflect the sum of uPA/uPAR activity in various tissues. uPAR has been shown to scavenge vitronectin, a glycoprotein involved in coronary atherosclerosis. In experimental models, uPAR was involved in the modulation of TGFβ-1 related post-infarction fibrosis and scar healing, and regulation of apoptosis, suggesting a possible direct role for suPAR in the pathogenesis of myocardial diseases. Asymmetric dimethylarginine, a marker of oxidative stress, has also been shown to correlate with suPAR levels.