The Shiu Research Laboratory is devoted to laboratory and clinical research related to hemodialysis vascular access, vascular dysfunctions in chronic kidney disease and mechanobiology of vascular cells in health and in disease.
Major Areas of Focus
One of our major areas of focus is the investigation of the pathophysiology of hemodialysis vascular access failure, as well as strategies to inhibit vascular access stenosis. Performance of a successful hemodialysis procedure requires a functional vascular access, which is a surgically-created blood conduit and the site on the patient’s body where blood is removed and returned during dialysis. Unfortunately, these conduits often fail and vascular access dysfunction is a major cause of morbidity and hospitalization in the hemodialysis population. No clinical therapies are currently available to significantly prevent or treat vascular access dysfunction. There are three main forms of vascular access: (1) the native arteriovenous fistula, (2) the synthetic arteriovenous graft, and (3) the cuffed double-lumen catheter. Each form has its own specific problems leading to failure. Dr. Shiu’s Research Laboratory is devoted to laboratory and clinical research related to understanding the pathophysiology of vascular access failure, and developing novel approaches to improve vascular access longevity and function. We aim to identify new mechanotransduction pathways responsible for neointimal hyperplasia formation in and failure of arteriovenous grafts and fistulas. We also aim to understand the role of extracellular matrices in hemodialysis vascular access failure. The results have the potential for broad applications in other vascular pathological conditions.
Another major area of focus is the investigation of the biomechanics of hemodialysis vascular access. In arteriovenous grafts and fistulas, shunting of arterial blood flow directly into the vein alters the hemodynamics in the vein. We believe that aberrant hemodynamic changes are major contributors to vascular access failure. Detailed hemodynamic changes in the arteriovenous conduits are not yet fully understood, partly because of the technical challenges, especially those that are required to assess the deformation of the thin venous wall. We have made significant progress in establishing these techniques in recent years. We have used imaging-based computational fluid dynamics to characterize the complex blood flow patterns and fluid shear stress in human and porcine arteriovenous accesses. We also have used imaging-based finite element analysis to measure the deformation of thin venous wall under arterial pressure at high resolution and calculate the wall stress. We also use elastography and other strain analysis methods for in vivo measurement of vein mechanics. These state-of-the-art techniques have broad applications in the biomechanics fields.
We also have substantial experience in (1) investigating cell responses to mechanical stimulation using in vitro and ex vivo models where cells are exposed to mechanical loading that closely approximates in vivo conditions; (2) using imaging-based modeling to characterize mechanical environments in vivo; (3) exploring how vascular cells sense and react to altered blood flow rate/pressure and how hemodynamic stress contributes to vascular wall remodeling. Our laboratory is fully equipped for research projects in these areas, and our methods are state-of-the art techniques.