| Description | Molecular Engineering and Sciences Seminar Series
Abstract: In-Vivo Molecular Engineering with Focused Ultrasound Concentrating ultrasound into an exceptionally small focus (i.e. focused ultrasound) permits, under image-guidance, the precisely targeted deposition of energy deep into soft tissues. By tuning the ultrasound application parameters, the resultant energy deposition may range from an almost purely thermal regime to an almost purely mechanical regime. Thus, in essence, focused ultrasound represents a versatile tool for engineering molecular responses in-vivo via thermal and mechanical modulation of the tissue microenvironment. Our group leverages these molecular level responses for several biomedical applications. Thermal focused ultrasound is used in sparse ablation patterns to generate regions of heat-shocked cells in solid tumors that, in turn, potentiate the ability of immunotherapies to recognize and control metastatic disease. Our work in this area supports clinical trials at UVA that rationally combine focused ultrasound with immunotherapies for breast cancer and other neoplasms. In contrast, we use mechanical focused ultrasound primarily as a tool to temporarily “engineer” the molecular structure of the blood-brain barrier. Specifically, we are able to safely disrupt the blood-brain barrier in highly localized regions to permit drug and gene-bearing nanoparticle delivery. This is done primarily in the context of pre-clinical models of Parkinson’s Disease and primary and metastatic brain tumors. Finally, we have recently developed the concept of “sonoselective” transfection of cerebrovascular endothelium. Here, mechanical focused ultrasound is carefully tuned to yield gene delivery specifically to endothelial cells in the brain, without using an endothelial cell-specific promoter. We envision this approach may have utility as a tool for stimulating hippocampal neurogenesis, inhibiting or reversing vascular cognitive impairment, and/or improving drug delivery to the CNS via blockade of blood-brain barrier efflux transporters.
This weekly seminar brings together students, faculty and invited guests from various disciplines across campus to explore current trends in molecular engineering and nanotechnology. It is a forum for active interdisciplinary discussions. These talks are open to the public and attract a diverse audience of students and faculty. |
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