Micro-managing Atherosclerosis by Mechanosensitive “Athero-miRs”
12:30 – 1:30pm, Foege N130A (Wallace H. Coulter Seminar Room)
Atherosclerosis is the major underlying cause of myocardial infarction and stroke and preferentially occurs in arterial regions exposed to disturbed flow (d-flow) by mechanisms involving broad changes in gene expression. We have shown that D-flow rapidly induces atherosclerosis in vivo using a mouse partial carotid ligation model. In addition, we developed a novel intimal RNA preparation method using this animal model and identified numerous mechanosensitive endothelial genes that change in response to d-flow. Some of these mechanosensitive genes are regulated by microRNAs (miRNAs). While miRNAs are known to regulate various aspects of cardiovascular biology and disease, their role in atherosclerosis is unclear. Recently, we identified novel mechanosensitive miRNAs using the same mouse model and endothelial miRNA array. We employed an integrative approach, combining systems biology with functional genomics in a single experimental animal model to overcome a major obstacle in miRNA research: linking individual miRNA changes to a network of potential target genes in an unbiased manner to identify relevant molecular pathways and generate specific, testable hypotheses. I will discuss the role of mechanosensitive miRNA in endothelial function and atherosclerosis. Our results suggest that targeting mechanosensitive “athero-miR” with anti-miR-based approaches may provide a new treatment paradigm in atherosclerosis.
Dr. Hanjoong Jo is John and Jan Portman Professor of Biomedical Engineering (BME) at Georgia Tech and Emory University, and Professor of Medicine at Emory University. He is also the Associate Chair of Emory Affairs in BME. Dr. Jo received PhD in Physiology under the co-mentorship of John Tarbell (Chemical Engineering) and Ted Hollis (Physiology) at Pennsylvania State University in 1989. Upon postdoctoral training in Jay McDonald Lab at Washington University and University of Alabama at Birmingham, he became Assistant Professor in Pathology and BME in 1995. Dr. Jo joined the BME Department at Georgia Tech and Emory University in 2000. He directs the Cardiovascular Mechanobiology and Nanomedicine lab at Emory University. His lab studies how mechanical force associated with blood flow regulates vascular biology and cardiovascular disease, especially atherosclerosis and aortic valve (AV) calcification. He has published more than 130 peer-reviewed papers and edited a book. He is an elected fellow of American Heart Association and American Physiological Society. He serves as associate editors and editorial board members of several cardiovascular and biomedical engineering journals including Circulation Research, Atherosclerosis Thrombosis Vascular Biology, Am J Physiology, Cell Molecular Bioengineering and Cardiovascular Engineering and Technology. He also has been serving as reviewers and chairs of study sections of several funding agencies including the NIH and Am Heart Association. He also co-organized several national and international meetings, and in 2012, he served as the Chair of the Annual BME Society Meeting.