University of Vermont

College of Medicine

Department of Pathology and Laboratory Medicine

doyle_lab

Doyle Lab Research

Research

Our overall research is geared towards better understanding the role of circulating biomarkers for human disease.  All too often we look for one answer to very broad disease states. Terms such as cardiovascular disease, cancer, and aging are very broad terms for what has turned out to be very complicated diseases involving genetics, environment and viral or bacterial challenges. Each individual has a different contribution from each area, thus having a unique biomarker profile. If we can understand an individual profile for disease, we can provide better targeted medical interventions.

Overview of current areas of research

Endothelial Progenitor Cells and circulating endothelial cells in COPD: We are currently measuring endothelial progenitor cells and circulating endothelial cells in a case control study of chronic obstructive pulmonary disease. Circulating endothelial progenitor cells are thought to be a measure of vascularization, while circulating endothelial cells are thought to be a measure of endothelial breakdown. We are looking for differences in each of these measures and the two taken together as an indication of progression of chronic obstructive pulmonary disease.

The role of innate and adaptive immune cells in atherosclerosis: We have determined cellular levels of a variety of immune cells (T cells, T helper cells, Th1, Th2, gd T cells, natural killer cells, memory T helper cells, naïve T helper cells, endothelial progenitor cells and resting and stimulated monocyte tissue factor levels) from ~1000 people of various ethnic background. These participants have been followed for >10 years with various information collected, including cardiovascular, anthropometric, nutrition and exercise, as well as blood, urine and cellular components. We have demonstrated that circulating Th1 levels show a positive correlation to the coronary artery calcium as well as intima media thickness. The Th1 level appears to be driven, to a large part, by the titer of CMV in the participant. The exact mechanism for this remains to be elucidated. The role of these immune cells in other disease states in currently under investigation. We are also attempting to find plasma markers for these cells that will allow estimation of cell types from stored plasma samples.

The nature of soluble cellular receptors circulating in blood: As soluble receptors found circulating in the blood appear to play a role in disease, we set forth to determine the exact nature of these soluble receptors. Of current interest are the soluble Il6 receptor, the soluble CD14 receptor and the soluble IL2 receptor alpha. ; These receptor may exist in three forms: a full length form that remains associated with lipid as a microparticle circulating through blood, an ectodomain form that has been cleaved from the cell by a “sheddase”, or an alternatively spliced soluble form that is released from cellular granules. We are using gel filtration column chromatography, SDS gel electrophoresis and western blooting techniques to determine which type or types exist in plasma, if different types exist in different people, and if different types exist between disease states.

Last modified June 11 2012 12:19 PM