Keith Neeves
Assistant Professor
Research Description
The long-term goal of our research is to develop methods that can predict an individual’s bleeding potential. Bleeding potential refers to the ability of your blood to form a stable blood clot. Certain genetic bleeding disorders like hemophilia and von Willebrand disease diminish an individual’s ability to form a stable clot. While diseases like myocardial infarctions, stroke, and deep vein thrombosis are examples of unrestrained clot growth, which is known as thrombosis and is the leading cause of death in the United States.
The difficulty in predicting bleeding potential is partially due to the complex interaction between coagulation, vascular injury, and hemodynamics. Our approach is to combine these three elements into in vitro flow assays of bleeding potential. These assays are different than most conventional bleeding assays because they incorporate hemodynamics, or blood flow. We are using a microsystems approach to improve the throughput and sensitivity of flow assays in an effort to move them into a clinical setting.
On a more fundamental level, we are interested in characterizing the molecular transport within clots. A blood clot can be treated as a porous medium with homogenous and heterogeneous reactions occuring on the surface of platelets. From a chemical engineering perspective, this falls into a class of problems characterized by low Reynolds number flow and high Peclet numbers (convection dominated transport). Understanding the biochemical events that occur in between platelets in a clot is critical to our understanding of clot stability. Furthermore, in designing better “clot busting” drugs for stroke and myocardial infarctions, we need to understand what characteristics of a drug or drug delivery system will enhance penetration into a clot.
Visit our lab web page for a more information on current projects in the lab.
selected Publications
K.B. Neeves, C.T. Lo, C.P. Foley, W.M. Saltzman, and W.L. Olbricht. Fabrication and characterization of microfluidic probes for convection enhanced drug delivery. Journal of Controlled Release, 111 (2006), 252-262.
KB. Neeves, A.J. Sawyer, C.P. Foley, W.M. Saltzman, and W.L. Olbricht. Dilation and degradation of the brain extracellular matrix enhances penetration of infused polymer nanoparticles. Brain Research, 1180 (2007), 121-132.
U.M. Okorie, W.S. Denney, M.S. Chatterjee, K.B. Neeves, and S.L. Diamond. Determination of surface tissue factor thresholds that trigger coagulation at venous and arterial shear rates: amplification of 100 fM circulating tissue factor requires flow. Blood, 111 (2008), 3507-3513.
K.B. Neeves and S.L. Diamond. A membrane-based microfluidic device for controlling the flux of platelet agonists into flowing blood. Lab on a Chip, 8 (2008), 701-709.
K.B. Neeves, S.F. Maloney, K.P. Fong, A.A. Schmaier, M.L. Kahn, L.F. Brass, and S. L. Diamond. Microfluidic focal thrombosis model for measuring murine platelet deposition and stability: PAR4 signaling enhances shear-resistance of platelet aggregates. Journal of Thrombosis and Haemostasis, 6 (2008), 2193-2201.