Scott Simon,
Professor of Biomedical Engineering,
University of California-Davis
An Established Investigator of the American Heart Association, Professor Simon's work on chronic inflammation focuses on structure-function studies of integrin and selectin receptors and vascular dysfunction during atherosclerosis. His laboratory was the first to discover the signaling functions of L-selectin and E-selectin. More recently, his group has developed novel microfluidic vascular mimetic lab-on-a-chip systems that provide real time imaging of force and molecular dynamics in leukocyte-endothelial interactions under defined shear stress. A recently funded project on atherogenesis aims to develop artery-on-a-chip devices to gauge the inflammatory potential of native lipoproteins and molecular events underlying monocyte recruitment to endothelium conditioned with lipids collected from normal and metabolic syndrome subjects. These approaches provide low cost, real time tools to study the tissue level consequences and biomarkers to assess disease progression. Another funded project with the Krubitzer laboratory in the Center for Neuroscience applies microfluidic thermal regulators that were developed to reversibly cooling and deactivate specific areas of the neocortex. The goal of these studies is to examine changes in receptive field size and location for neurons during and after cooling posterior parietal and motor/premotor cortex.
On-chip Phenotypic Analysis of Inflammatory Monocytes in Atherogenesis and Myocardial Infarction
Thursday, 18 September 2014 at 09:45
Add to Calendar ▼2014-09-18 09:45:002014-09-18 10:45:00Europe/LondonOn-chip Phenotypic Analysis of Inflammatory Monocytes in Atherogenesis and Myocardial InfarctionLab-on-a-Chip, Microfluidics and Microarray World Congress in San Diego, California, USASan Diego, California, USASELECTBIOenquiries@selectbiosciences.com
Acute myocardial infarction (MI) associated with coronary artery disease affects more than 2.5 million Americans annually and is a major cause of mortality worldwide. While stable coronary artery disease (CAD) can be promptly diagnosed through stress testing and angiography, plaque rupture due to atherosclerosis remains highly unpredictable. Furthermore, studies have shown that 50% of patients with MI lack the traditional risk factors for CAD, including elevated low-density lipoprotein cholesterol, fasting triglycerides, hypertension, and diabetes. Therefore, there is a clinical need for non-invasive assays of inflammatory cell activation to gauge its role in atherogenesis. Based upon relative expression of the monocyte markers CD14 and CD16 we assessed their numbers with the onset of CAD. These were identified by flow cytometry and their numbers in circulation increased in high risk subjects postprandial following a high fat meal, and in MI patients before treatment. In these high risk and CAD cohorts, we examined adhesion molecule expression on monocyte subsets and found that a member of the€ß2-integrin family associated with atherosclerosis, CD11c/CD18, was upregulated 60% on CD14++CD16+ inflammatory subset of monocytes. Furthermore, CD11c was upregulated 300% on patients undergoing an MI compared to healthy subjects. Since the integrins CD11c and VLA-4 support monocyte recruitment on VCAM-1, we sheared subject’s whole blood in our vascular mimetic microfluidic flow channels over recombinant VCAM-1. We detected a ~25% increase in enrichment of CD14++CD16+ monocytes postprandial and an ~80% increase for MI patients. There was no significant enrichment of the other monocyte subsets. This lecture will describe a lab on a chip approach to define the respective roles of CD11c as a biomarker of CAD and activator of VLA-4 dependent adhesion on VCAM-1 in high risk subjects and those experiencing MI.
Add to Calendar ▼2014-09-18 00:00:002014-09-19 00:00:00Europe/LondonLab-on-a-Chip, Microfluidics and Microarray World CongressLab-on-a-Chip, Microfluidics and Microarray World Congress in San Diego, California, USASan Diego, California, USASELECTBIOenquiries@selectbiosciences.com
Add to Calendar ▼2014-09-18 09:45:002014-09-18 10:45:00Europe/LondonOn-chip Phenotypic Analysis of Inflammatory Monocytes in Atherogenesis and Myocardial InfarctionLab-on-a-Chip, Microfluidics and Microarray World Congress in San Diego, California, USASan Diego, California, USASELECTBIOenquiries@selectbiosciences.com
