CAREER: Vascular Gene Therapy: Characterization and Optimization

9985012 chesler基因治疗是治疗和预防血管疾病的一种令人兴奋的新方式。工程基因治疗递送技术可以使这项技术更经济实惠，从而广泛地为心血管患者提供服务。通过将定量工程分析应用于活的生物系统，PI希望进一步了解人类血管运输机制（目标1），优化腺病毒基因治疗方法（目标2），并评估优化的基因治疗策略在人类动脉和静脉中的疗效（目标3）。体外血管培养系统将用于实现这些目标。离体动脉和静脉器官培养是研究严格环境和机械控制下血管转运现象的理想实验范式。此外，它允许在三维的、接近生理的环境中进行活体人体组织实验。提出的职业规划的第一个教育目标是教授工程专业学生PI专业领域的基础知识：热流体科学（目标1）。将采用基于问题的学习技术和与当地工业的互动来实现这一目标。第二个目标是加强研究生和本科生工程师的团队合作和沟通技巧（目标2）。具体来说，学生将在课堂上获得设计项目，并被分配到混合级别和混合性别的团队。他们将通过向他们的同龄人和外行观众（当地的中学生）做演讲来指导技术交流和实践。教育计划的第三个目标是解决工程劳动力多样性的问题（目标3）。大学级别的指导将是频繁和非正式的。通过在大学、高中和初中阶段的推广和指导，PI希望增加工程领域的女性人数。

9985012CheslerGene therapy is an exciting new modality for treating and preventing vascular disease. Engineered gene therapy delivery techniques could make this technology more affordable and thus broadly accessible to the cardiovascular patient population. By applying quantitative engineering analyses to a living, biological system, the PI hopes to further our knowledge of human vascular transport mechanisms (aim 1), optimize adenoviral gene therapy methods (aim 2), and assess the efficacy of optimized gene therapy treatment strategies in human arteries and veins (aim 3). An ex vivo vascular culture system will be used to pursue each of these goals. Ex vivo arterial and venous organ culture is an ideal experimental paradigm for investigating vascular transport phenomena under rigorous environmental and mechanical control. Further, it allows living human tissue experimentation in a three-dimensional, near-physiological environment. The first educational goal of the proposed career plan is to teach engineering students the fundamentals in the PI's area of specialization: the thermofluid sciences (aim 1). The techniques of problem-based learning and interaction with local industry will be used to achieve this goal. The second aim is to strengthen teamwork and communication skills in both graduate and undergraduate engineers (aim 2). Specifically, students will be given design projects in classes and assigned to mixed-level and mixed-gender teams. They will be given instruction in technical communication and practice by giving presentations to their peers and a lay audience (local middle-school children). The third goal of the educational program is to addresses the problem of diversity in the engineering workforce (aim 3). University-level mentoring will be frequent and informal. Through outreach and mentoring at the university, high school and middle school levels, the PI hopes to increase the number of women in engineering and in the pipeline.