CAREER: EMBRACE STEM (Endothelial MechanoBiology Research And multiCultural Education in STEM)

流体(血液)和固体(血管壁)力都是血管自然机械环境的一部分，决定着血管的功能。血管属性的变化--通常是由于年龄或疾病--会影响排列血管的细胞(内皮细胞)的活动，后者随后会做出反应，并进一步影响血管的属性。这项教师早期职业发展计划(Career)研究项目将检验一个两层假设，以进一步理解这种相互作用。首先，假设流体和固体力量共同作用来调节血管壁上的内皮细胞的行为。这些细胞检测这些力量，并作为回应，引导血管功能以维持健康。其次，假设对内皮细胞作用力的生物反应(这一过程称为机械生物学)是通过糖萼发生的，这是一层固定在内皮细胞上并覆盖着内皮细胞的糖层。这一职业研究项目将解决关于这些血管衬里细胞如何对其机械环境做出反应的关键知识空白，这一知识空白限制了血管疾病预防和治疗的成功。新的知识将使我们有可能设计出控制内皮细胞机械生物学的创新方法，并改变我们修复或再生血管内皮细胞功能的方式。STEM(科学、技术、工程和数学)教育和推广活动将与研究相结合，对机械生物学研究和STEM劳动力产生积极影响。K-12、本科生、硕士和博士生组成的一般和代表性较低的少数群体将通过体验式学习活动参与和培训--从K-3学生的动手挑战到科学博览会项目到论文--这将由职业研究项目催化。首席调查员将担任代表性不足的少数族裔教练，还将为年龄较大的学生提供指导较年轻学生的机会。该项目教育部分的目标是，在不久的将来，扩大各级STEM教育，在长期内，扩大STEM劳动力的多样性，以加强创新。该项目的总体研究目标是通过机械生物学来确定血管调节的内皮细胞和糖萼机制。已经确定了三个目标。首先，描述在一系列流体-固体机械刺激组合下的糖萼的结构。第二，将糖萼的机械控制结构与驱动内皮细胞反应的主角和拮抗剂分子机制的激活联系起来。最后，阐明机械刺激、糖基化刺激和分子刺激在多大程度上在血管内皮细胞内引起影响血管功能的反应。这份职业计划的总体教育目标是指导和支持不同文化背景的学生拓宽未来的劳动力，利用新的视角，并加强内皮细胞机械生物学研究的创新。这将通过建立一个包容性的STEM社区来实现，该社区包括为研究生、本科生和高中生提供研究经验、指导和财务支持--特别强调来自代表不足的群体的学生--他们然后回到K-8学生那里，让他们对STEM感到兴奋。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Fluid (blood) and solid (blood vessel wall) forces are both part of the natural mechanical environment of blood vessels and determine blood vessel function. Changes in the properties of blood vessels -- often due to age or disease - can influence the activity of the cells that line the blood vessels (endothelial cells), which can subsequently respond and further affect the properties of the vessel. This Faculty Early Career Development Program (CAREER) research project will test a two-tier hypothesis to further understand this interaction. First, it is hypothesized that the fluid and solid forces work together to regulate behavior of the endothelial cells that line the blood vessel wall. These cells detect these forces, and, in response, guide blood vessel function to maintain health. Second, it is hypothesized that the biological response to force by the endothelial cells (a process called mechanobiology) occurs via the glycocalyx, which is a sugar layer that is anchored to and coats endothelial cells. This CAREER research project will address a critical gap in knowledge about how these vascular lining cells respond to their mechanical environment, a knowledge gap which has limited the success of vascular disease prevention and treatment. New knowledge will make it possible to engineer innovative approaches to control endothelial cell mechanobiology and transform how we repair or regenerate endothelial cell function in blood vessels. STEM (science, technology, engineering, and math) education and outreach activities will be integrated with the research in a manner that will positively impact both mechanobiology research and the STEM workforce. General and underrepresented minority populations of K -12, undergraduate, masters, and doctoral students will be engaged and trained through experiential learning activities -- ranging from hands on challenges for K-3 students to science fair projects to dissertations -- which will be catalyzed by the CAREER research project. The principal investigator will serve as an underrepresented minority coach, and opportunities will also be provided for older students to mentor younger students. This goal of the educational portion of this project is to, in the near future, expand STEM education at all levels and, in the long-term future, expand the diversity of the STEM workforce to enhance innovation.The overall research goal of this project is to define the endothelial cell and glycocalyx mechanisms of blood vessel regulation through mechanobiology. Three objectives have been established. First, to characterize the architecture of the glycocalyx over a range of combined fluid-solid mechanical stimuli. Second, to link the mechanically-controlled architecture of the glycocalyx to the activation of both protagonist and antagonist molecular mechanisms that drive the response of endothelial cells. And finally, to clarify the extent to which cooperative mechanical, glycocalyx, and molecular stimuli evoke a response within the endothelial cells that impacts blood vessel function. The overall educational objective of this CAREER proposal is to coach and champion culturally diverse students to broaden the future workforce, leverage new perspectives, and enhance endothelial cell mechanobiology research innovation. This will be approached by building an inclusive STEM community that includes research experiences, mentoring, and financial support for graduate, undergraduate, and high school students -- with special emphasis on students from underrepresented groups -- who then reach back to K-8 students to excite them about STEM.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.