The overall focus of the Taylor basic science laboratory is to gain a better understanding of the role of inflammation in cardiovascular disease. Inflammation has diverse effects on the cardiovascular system, some positive others pathological. Maladaptive inflammation is a common theme in many disease states and is especially important to most cardiovascular diseases. The Taylor lab has focused on obtaining a better understanding of the mechanisms and consequences of inflammation in cardiovascular disease with an ultimate goal of developing improved therapies that target inflammation. We are also interested in the beneficial effects of vascular inflammation and have studied these in the setting of collateral vessel formation.
Much of our previous work has examined the regulation of inflammation via reactive oxygen species in the setting of abnormal biomechanical or humoral stimuli. Our work in the renin-angiotensin system has helped to define the role of angiotensin II in atherosclerosis and hypertensive vascular disease. Through unique collaborations with other investigators at Emory as well as those at Georgia Tech and Emory College, we have explored the impact of biomechanics on the vasculature with a specific interest in atherosclerosis and abdominal aneurysm formation.
Finally, we have become interested in cell-based approaches as immuno-modulatory therapies for cardiovascular disease. We are interested in the potential paracrine effects of cell-based therapies with a specific focus on the capacity of cell therapies to modulate inflammation with therapeutic benefit to the cardiovascular system.
Research Projects
Examining the Mechanisms Responsible for the Formation of Abdominal Aortic Aneurysms
We are currently broadly examining the mechanisms responsible for the formation of abdominal aortic aneurysms. At the molecular level, we are examining the role of hydrogen peroxide as a pivotal signaling mechanism for aneurysm formation and growth. Hydrogen peroxide normally functions as a homeostatic signaling molecule that regulates cell proliferation and migration. In the earliest stages of aneurysm formation, it is produced in excess and promotes a potent pro-inflammatory state. On a larger scale, we are studying the role of vascular biomechanics in abdominal aortic aneurysm formation. Abdominal aortic aneurysms form at a specific location in the abdominal aorta that appears to be pre-determined by local hemodynamic forces. To accomplish this latter goal, our research involves MRI of healthy human subjects coupled with computational modeling to better define the role of local biomechanical forces in aneurysm formation.
Defining the Role of the Pro-Inflammatory Extracellular Matrix Protein, Osteopontin, in the Process of Neo-Vascularization
We are also interested in defining the role of the pro-inflammatory extracellular matrix protein, osteopontin, in the process of neo-vascularization. Our lab is interested in determining how the human OPN isoforms, a, b, and c, deferentially affect cell migration and cell signaling and how this translates to changes in new vessel formation and perfusion in models of ischemia. Additionally, we are interested in changes in vascular production of Osteopontin in response to high blood pressure and cardiovascular stress.
Mesenchymal Stem Cells (MSC) as therapy to ischemic tissues
Cell based therapies are a promising new approach for treating patients with a myocardial infarction or critical limb ischemia. One mechanism through which this approach may work is modulating the inflammatory response in the ischemic tissues. However, current methods are limited due to inability of the stem cells to remain and survive in damaged tissues. Our lab is investigating new biomaterials as a novel way to deliver stem cells to ischemic tissues and the subsequent impact on the local inflammatory state.
Diabetes
Diabetes is another disease state in which dysregulation of inflammation results in adverse effects on the vasculature. One of the key regulatory steps for inflammation in diabetes involves the receptor for advanced glycation endproducts (RAGE). Work in the laboratory has centered in understanding the role of RAGE in regulating inflammation and subsequent collateral vessel formation.
Imaging Bacteria in the Setting of Infections of Cardiac Devices
A unique area of interest in the lab is to develop agents for imaging bacteria in the setting of infections of cardiac devices. Infection of pacemakers and defibrillators is an important cause of morbidity and mortality in cardiac patients, but it is often difficult to diagnose these infections. We are currently developing novel molecular PET and fluorescent probes to image bacteria with high specificity and sensitivity in order to improve on currently available techniques and detect these infections earlier.