BME PhD Proposal Presentation
Date: Monday, December 10 (Atlanta) / Tuesday, December 11 (Beijing)
Time: 8:00 PM (Atlanta) / 9:00 AM (Beijing)
Location: Video conference (Atlanta, see below for connection info*) / No.1 Building of COE, Room 212 (PKU)
Zhifei, Dai (Advisor, PKU-BME)
Hanjoong Jo (Co-Advisor, GT-BME)
Brooks Lindsey (GT-BME)
Qiang Zhang (PKU- School of Pharmaceutical Sciences)
Xiaolong Liang (PKU- Third Hospital)
Ultrasound-guided transgene expression of KLK10 to inhibit atherosclerosis
Atherosclerosis is the leading causes of death worldwide. Atherosclerotic plaques preferentially develop in regions exposed to disturbed flow. Vascular endothelial cells respond to blood flow through mechanosensors, which transduce the shear stress associated with flow into cell signaling events and ultimately result in proatherogenic responses. Our recent studies show that KLK10 is an important atheroprotective gene, which is downregulated by disturbed flow. Therefore, transgene expression of KLK10 gene in vivo to normalize the dysfunctional endothelial cells is a promising therapy. However, targeted gene delivery to vascular endothelial cells remains a hard task.
Ultrasound as a cheap, noninvasive, non-ionizing and real-time imaging technique is an ideal tool for progress monitoring of atherosclerosis. At high power, ultrasound combined with microbubbles has been demonstrated to facilitate gene delivery. We propose to use ultrasound combined with microbubbles to induce transgene expression of KLK10 in vivo from two aspects. On one hand, we will use Doppler-mode ultrasound imaging combined with microbubbles to increase the permeability of carotid artery. After that, adeno-associated virus (AAV) carrying KLK10 gene will be injected, hoping that KLK10 can be expressed in the arterial endothelium of the selected area. On the other hand, the microbubble-mediated sonoporation is expected to induce enhanced KLK10 transgene expression in skeletal muscles. The transgene expression may provide sustained KLK10 proteins in circulation, and thus inhibit atherosclerosis.
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