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

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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.