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

职业：拥抱 STEM（内皮力学生物学研究和 STEM 中的多文化教育）

基本信息

批准号：
1846962
负责人：
Eno Ebong
金额：
$ 50万
依托单位：
Northeastern University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1846962&HistoricalAwards=false
关键词：
CAREER EMBRACE STEM Endothelial MechanoBiology

项目摘要

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.

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，并确定血管功能。血管特性的变化（通常是由于年龄或疾病引起的）会影响排列血管（内皮细胞）的细胞的活性，后者随后可以反应并进一步影响血管的性质。这个教师早期职业发展计划（职业）研究项目将检验一个两层假设，以进一步了解这种互动。首先，假设流体和固体力共同调节排列血管壁的内皮细胞的行为。这些细胞检测到这些力，并反应引导血管的功能维持健康。其次，假设内皮细胞对力的生物学反应（一种称为机械生物学的过程）通过糖卵形化发生，该糖层是一种糖层，糖层固定在和涂层内皮细胞上。该职业研究项目将解决有关这些血管内膜细胞如何响应其机械环境的重要差距，这一知识差距限制了预防血管疾病和治疗的成功。新知识将使设计创新的方法来控制内皮细胞机械生物学，并改变我们修复或再生血管中内皮细胞功能的方式。 STEM（科学，技术，工程和数学）教育和外展活动将与研究融合，以对机械生物学研究和STEM劳动力的积极影响。 K -12，本科生，硕士和博士生的一般和代表性不足的少数群体将通过体验式学习活动进行参与和培训 - 从K -3学生的挑战到科学公平项目，再到论文 - 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，还将为年长学生提供指导年轻学生的机会。该项目的教育部分的目标是，在不久的将来，在各个层面上扩大了STEM教育，并在长期的未来扩大了STEM劳动力的多样性，以增强创新。该项目的总体研究目标是定义内皮细胞和糖核酸的糖脂机制，通过机械生物学来定义血管调节的机制。已经建立了三个目标。首先，要在一系列混合流体固定的机械刺激上表征糖卵形的结构。其次，将糖椰子的机械控制结构与主角和拮抗剂分子机制的激活联系起来，这些机制驱动了内皮细胞的反应。最后，为了阐明合作机械，糖椰子和分子刺激的程度，引起了内皮细胞中影响血管功能的反应。这项职业建议的总体教育目标是指导和拥护文化多样的学生，以扩大未来的劳动力，利用新观点并增强内皮细胞机械生物学研究创新。将通过建立一个包容性的STEM社区来解决这一问题，该社区包括研究经验，指导和为研究生，本科生和高中生的财政支持 - 特别强调来自代表性不足的团体的学生 - 然后向K-8学生兴奋地激发了他们对STEM的兴奋。该奖项反映了NSF的法定任务，并通过评估师来的构成群体的范围来表现出众所周知的范围。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Regeneration and Assessment of the Endothelial Glycocalyx To Address Cardiovascular Disease

DOI：
10.1021/acs.iecr.1c03074
发表时间：
2021-12-08
期刊：
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
影响因子：
4.2
作者：
Banerjee, Selina;Mwangi, John G.;Ebong, Eno E.
通讯作者：
Ebong, Eno E.

New In Vitro Model to Study Multicellular and Flow Control of Blood‐Brain Barrier

研究血脑屏障的多细胞和流动控制的新体外模型

DOI：
10.1096/fasebj.2022.36.s1.l7754
发表时间：
2022
期刊：
The FASEB Journal
影响因子：
0
作者：
O'Hare, Nicholas R.;Harding, Ian;Vigliotti, Mark;Caraballo, Alex;Lee, Claire;Herman, Ira;Ebong, Eno E.
通讯作者：
Ebong, Eno E.

Atherosclerosis and endothelial mechanotransduction: current knowledge and models for future research