RESEARCH OVERVIEW

Summary:

The primary focus of our research is on atherosclerosis, a disease of the blood vessels that leads to heart attack and stroke.  We are interested in why the disease shows up predictably in certain areas of the blood vessels and not others--a phenomenon that correlates closely with the local fluid mechanics of the blood.  We study the response of vascular endothelial cells to different flow characteristics to determine what might predispose the cells to disease in one case, or resistance in another.  We also seek to understand how risk factors for the disease such as “bad fats” or aging affect the disease process.  There is still much to be learned with respect to the mechanisms by which the endothelium integrates these diverse physiological cues to impact health and disease.  Our laboratory uses cell culture models and state-of-the-art technologies to probe the biology of the cell at a number of levels--from gene expression to functional outcomes such as monocyte recruitment--to help elucidate these mechanisms.  A better understanding of these mechanisms would help guide the development of novel strategies to prevent, diagnose and treat disease.

Current projects include: 

Vascular mimetic approaches to study inflammation and susceptibility to atherosclerosis.

This particular project is representative of our broad interest in how risk factors for cardiovascular disease converge with endothelial mechanobiology.  This project entails the use of in vitro cell culture models that mimic the early stages of disease in the blood vessels by simulating the effects of a high fat diet in the context of physiological flows and stresses.  This is a successful collaboration with Dr. Simon’s group.

Influence of endothelial cell aging on the inflammatory mechanisms of atherogenesis.

Aging is an important risk factor associated with atherosclerosis.  In this study we seek to understand how aging of the blood vessels makes them more susceptible to disease.  We propose that age-associated changes in the cells which line the blood vessels will impair their function and make them more susceptible to the disease process. 

Characterization of molecular signatures of adipose derived stem cell (ADSC) differentiation.

ADSCs can be differentiated into bone-like cells for use in tissue engineering applications, but the mechanisms behind this are not well characterized.  We aim to identify markers associated with the process of differentiation.  Aging is also an important aspect of this project.  We are investigating whether cells from old or young donors behave the same with respect to their differentiation.  This is an important consideration when analyzing therapeutic potential.  This is a collaborative project with the Leach lab.