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

我实验室的工作重点是创建组织模型，模拟各种组织在体内状态的流体力方面。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因子，并对流动下组织功能的机制理解。在过去的五年中，我们已经将基于这些概念的发现和平台技术转化为多个专利申请，组建了4家公司，并在工程和技术领域雇用了多名学员。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。***近期目标（5年）：1)确定血管细胞血流介导基因表达的关键调节因子。2)发展新的成像和计算方法来量化体内流体流动和组织特征。3)建立正常乳腺组织模型，量化血流环境下基因表达和细胞功能变化。***长期目标（5-10年）：1)建立血流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联系起来，以绘制流体流动如何被用作调节细胞以创造或维持健康组织的兴奋剂。3)识别液体（如血液或牛奶）中可用于表征个体健康状况的分子特征。***意义与影响：本研究项目的创新点在于：1)阐明了流体流动环境中促进健康的机制；2)确定了流体流动相关的分子特征；3)开发了血管和乳腺健康特异性研究的测试平台。该项目将确定流体力敏感分子调节剂，这将有助于理解正常的人类血管和乳腺组织功能。这些信息将直接导致刺激-功能关系，用于预测血管和乳腺组织如何保持健康功能，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例，并将提供一种方法来测试新的治疗方法或设备，并确定健康的分子特征。***培训：本科生、研究生（博士和硕士）和一名博士后将进行研究，并成为合作团队的一员，推进与细胞流体力效应相关的知识和开发技术；获得宝贵的技能，为招聘进入生物技术，医疗设备和相关行业。

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.