Fluid flow Promotion of the Healthy State: Technology Platforms and Mechanisms

在我的实验室工作的重点是创建组织模型模仿流体力方面的各种组织的体内状态。 这些模型可用于测试细胞和组织生理学，发现细胞功能的关键调节剂，并开发流动下组织功能的机械理解。 在过去的五年里，我们已经根据这些概念翻译了发现和平台技术，提交了多项专利申请，成立了4家公司，并在工程和技术领域雇用了多名培训生。 在接下来的五到十年里，我们建议继续开发机械生物学的平台技术和知识，以促进健康和技术的进步。* 短期目标（5年）：1）确定血管细胞中流动介导的基因表达的关键调节剂。 2)开发新的成像和计算方法来量化体内液体流动和组织特征。 3)建立正常乳腺组织模型，量化流动环境中基因表达和细胞功能的变化。 * 长期目标（5-10年）：1）开发流动环境中内皮和上皮基因表达和功能的机制描述。 2)将内皮细胞和上皮细胞的流动反应与其他细胞类型的流动反应相关联，以绘制流体流动如何被用作刺激物，“调谐”细胞以创建或维持健康组织。3)识别液体（如血液或乳汁）中可用于表征个体健康状况的分子特征。* 意义和影响：本研究计划的创新在于：1）阐明流体流动环境中促进健康的机制，2）识别与流体流动相关的分子特征，3）开发用于血管和乳房健康特定研究的测试平台。这个项目将确定流体力敏感的分子调节器，这将有助于了解正常的人类血管和乳腺组织的功能。这些信息将直接导致刺激-功能关系，该关系将用于预测血管和乳腺组织如何维持健康功能，包括驱动生理反应的关键因素。这些关系将为理解健康提供一个新的范式，并将提供一种测试新疗法或设备并识别健康分子特征的方法。培训内容：本科生，研究生（博士和硕士）和博士后研究员将进行研究，并成为合作团队的一部分，推进知识和开发与流体力对细胞的影响相关的技术;获得招聘到生物技术，医疗器械和相关行业的宝贵技能。

Work in my lab is focused upon creating tissue models mimicking fluid forces aspects of the in vivo state of various tissues. These models can be used for testing cell and tissue physiology, discovering key modulators of cell function, and developing a mechanistic understanding of tissue function under flow. We have translated discoveries and platform technologies based on these concepts with submission of multiple patent applications, formation of 4 companies, and multiple trainees employed in the engineering and technology sectors in the past five years. Over the next five to ten years we propose to continue developing platform technologies and knowledge in mechanobiology to facilitate advances in health and technology. ***Short-term goals (5 years): 1) Identify key modulators of flow-mediated gene expression in blood vessel cells. 2) Develop new imaging and computational methods to quantify in vivo fluid flows and tissue characteristics. 3) Create normal breast tissue model and quantify gene expression and cell function changes in the flow environment. ***Long-term goals (5-10 years): 1) Develop a mechanistic description of endothelial and epithelial gene expression and function in a flow environment. 2) Correlate endothelial and epithelial flow responses to those in other cell types to map how fluid flow may be used as a stimulant that ‘tunes' cells for the creation or maintenance of healthy tissues. 3) Identify molecular signatures in fluids (such as blood or milk) that can be used to characterize health of an individual. ***Significance and Impact: The innovation in this research program is 1) elucidation of mechanisms of health promotion in fluid flow environments, 2) identification of molecular signatures associated with fluid flow, and 3) development of testing platforms for specific investigation of blood vessel and breast health. This project will identify fluid force sensitive molecular regulators that will aid in the understanding of normal human vascular and breast tissue function. This information will lead directly to a stimulus-function relationship that will be used to predict how blood vessels and breast tissue maintain healthy function, including the key factors driving physiological responses. These relationships will enable a new paradigm in understanding health, and will provide a way to test new therapeutics or devices and identify healthy molecular signatures.***Training: Undergraduate students, graduate students (PhD and MSc), and a postdoctoral fellow will perform the research and be part of collaborative teams advancing knowledge and developing technologies related to fluid force effects on cells; gaining valuable skills for recruitment into the biotechnology, medical device and related industries.