The vascular biology research laboratories in the Knight Cardiovascular Institute aim to uncover the underlying mechanisms of the vascular system, and to use that knowledge to prevent and treat cardiovascular disease. Our research focus is organized around microcirculation and its role in the prevention and treatment of microvascular disease, the cause of debilitating complications from chronic diseases like hypertension and diabetes. Current projects of interest include:
- Multi-departmental teams are working toward identifying the therapeutic target for microcirculation and ways to treat small vessel disease. Utilizing advanced imaging and transgenic animal models to understand microvascular networks and cell-cell interactions in the microcirculation.
- Uncovering processes in platelet function that can lead to therapeutic targets in the detection, prevention and treatment of cardiovascular diseases.
- Exploring the mechanisms underlying microvascular constriction and the disruption of neurovascular signaling in stroke.
We see microcirculation as the next frontier of discovery, innovation and medical breakthroughs in cardiovascular disease. Our scientific teams partner with physicians and industry to identify and resolve clinically significant cardiovascular problems.
Role of receptors
A team effort among the vascular biology laboratories and other departments across OHSU is involved in identifying those receptors essential to the function of microcirculation, with the goal of developing therapies to address chronic disease due to irregular blood flow. These teams are testing those receptors that will most effectively address small vessel disease, and the associated compounds that can be used to develop drugs that accomplish optimal blood flow in various cardiovascular conditions.
Current platelet research projects investigate how signaling systems regulate the cytoskeletal, secretory and procoagulant phenotypes that drive platelet function in hemostasis and thrombosis. Our work has uncovered roles for mTOR, PAK, protein kinase C (PKC), MAP kinase and other signaling networks in platelet physiology and associated cellular functions in general.
We use a range of systems biology based tools, including quantitative proteomics and bioinformatics pathway analysis, to interrogate novel pathways and molecular mechanisms of platelet function. Through this approach, we have recently uncovered roles for reversible protein lysine acetylation in platelet function and have developed insights into PKC and MAP kinases in regulating platelet activities. Additionally, using super-resolution microscopy tools such as SR-SIM and PALM, we have imaged microtubules, adhesion complexes and the actin cytoskeleton in platelets at unprecedented resolution.
Microvascular constriction and stroke
Our laboratory team has demonstrated that astrocytes regulate cortical microvascular flow by signaling to pericytes, and more importantly, that ischemia results in capillary constriction. Current research in our lab is testing the hypothesis that microvascular constriction occurs in vivo after a stroke, leading to a loss of energy supply, and that this is due to dysfunctional signaling from reactive astrocytes to capillary pericytes. We are also testing the mechanisms underlying the disruption of neurovascular signaling in stroke.