Collaborative Research: Deciphering the synergistic interaction between hemodynamics and genetics that form the heart
合作研究:破译形成心脏的血流动力学和遗传学之间的协同相互作用
基本信息
- 批准号:2109959
- 负责人:
- 金额:$ 32.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-06-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
During early cardiac development, blood flow and genetic processes influence each other to ensure formation of an efficient heart. However, how exactly genes and blood flow interact with one another during formation and growth of the heart remains largely unknown. This collaborative research between the University of California at Irvine (UCI) and the Oregon Health & Science University (OHSU) will use advanced imaging methods together with computational simulations to unravel how altered blood flow affects programmed genetic processes, and conversely how altering genetic processes changes blood flow, leading to hearts with defects. Results from this project will ultimately guide approaches to treat heart defects before a baby is born. To further broaden the impact of this project to the society, outreach activities involving rising high school sophomores, juniors, and seniors in California and Oregon, will engage the students in scientific activities with the goal of learning about heart development and cultivate team science skills. Although both blood flow and genetic processes contribute to heart development, how exactly they interact and affect each other, and the synergistic roles that blood flow and genetics play to predispose the heart to malformations are yet undetermined. The project’s intellectual merit is to elucidate interlinked connections between blood flow and genetic processes during heart development. More specifically, the project will study early changes in gene expression in response to altered blood flow, and early changes in blood flow in response to altered signaling, using two complementary avian models of heart development. The project will focus on three main objectives: (1) Determine blood flow and flow-induced stresses during normal and aberrant cardiac formation through advanced engineering methods; (2) Identify and quantify cellular responses to normal and perturbed heart development by generating spatiotemporal maps of cardiac adaptation; and (3) Determine the genetic and epigenetic adaptations in cardiac tissues due to early perturbations by DNA methylation and RNA sequencing. As the broader impact, results from this project will ultimately guide fundamental knowledge on embryonic heart development and help devise strategies to improve diagnosis of heart defects, prevent heart malformations, and eventually guide early fetal interventions to ameliorate the adverse effects of cardiac defects.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.
在心脏发育的早期,血流和遗传过程相互影响,以确保形成有效的心脏。然而,在心脏的形成和生长过程中,基因和血流究竟如何相互作用,在很大程度上仍然未知。加州大学欧文分校(UCI)和俄勒冈州健康科学大学(OHSU)之间的这项合作研究将使用先进的成像方法和计算模拟来揭示改变的血流如何影响编程的遗传过程,以及相反地改变遗传过程如何改变血流,导致心脏缺陷。该项目的结果将最终指导婴儿出生前治疗心脏缺陷的方法。为了进一步扩大该项目对社会的影响,加州和俄勒冈州的高中新生、大三和大四学生将参加外展活动,让学生参与科学活动,以了解心脏发育和培养团队科学技能。虽然血流和遗传过程都有助于心脏发育,但它们如何相互作用和相互影响,以及血流和遗传对心脏畸形的协同作用尚未确定。该项目的智力价值在于阐明心脏发育过程中血流和遗传过程之间的相互联系。更具体地说,该项目将使用两种互补的鸟类心脏发育模型,研究基因表达对血流改变的早期变化,以及血流对信号改变的早期变化。该项目将集中于三个主要目标:(1)通过先进的工程方法确定正常和异常心脏形成过程中的血流和血流诱导的应力;(2)通过生成心脏适应的时空图来识别和量化细胞对正常和扰动心脏发育的反应;和(3)通过DNA甲基化和RNA测序确定由于早期扰动引起的心脏组织中的遗传和表观遗传适应。作为更广泛的影响,该项目的结果将最终指导胚胎心脏发育的基础知识,并帮助制定改善心脏缺陷诊断,预防心脏畸形,并最终指导早期胎儿干预以改善心脏缺陷的不良影响。该奖项反映了NSF的法定使命,并通过使用基金会的智力价值和更广泛的影响审查标准。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mitochondrial transplantation in cardiomyocytes: foundation, methods, and outcomes
- DOI:10.1152/ajpcell.00152.2021
- 发表时间:2021-09-01
- 期刊:
- 影响因子:5.5
- 作者:Pour, Paria Ali;Hosseinian, Sina;Kheradvar, Arash
- 通讯作者:Kheradvar, Arash
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Arash Kheradvar其他文献
TCT-830 Immediate and Delayed Effects of Stent Crimping on Pericardial Leaflets of Transcatheter Valves
- DOI:
10.1016/j.jacc.2012.08.876 - 发表时间:
2012-10-23 - 期刊:
- 影响因子:
- 作者:
Arash Kheradvar;Hamed Alavi - 通讯作者:
Hamed Alavi
A NOVEL ASSESSMENT METHOD OF MULTIDIRECTIONAL 3D MYOCARDIAL FINITE STRAIN PATTERN FROM 3D ECHOCARDIOGRAPHIC DATA
基于三维超声心动图数据的多方向三维心肌有限应变模式的一种新颖评估方法
- DOI:
10.1016/s0735-1097(25)02565-3 - 发表时间:
2025-04-01 - 期刊:
- 影响因子:22.300
- 作者:
Satya Prakash Pradhan;Mohammad Hashemi;Arash Yavari;Gianni Pedrizzetti;Arash Kheradvar - 通讯作者:
Arash Kheradvar
DETERMINANTS OF LEFT VENTRICULAR VORTEX RING CIRCULATION IN REMODELED HEARTS: IMPROVED VISUALIZATION OF CARDIAC FLUID-STRUCTURE INTERACTIONS BY ECHO CONTRAST PARTICLE IMAGING VELOCIMETRY
- DOI:
10.1016/s0735-1097(11)60814-0 - 发表时间:
2011-04-05 - 期刊:
- 影响因子:
- 作者:
Haruhiko Abe;Giuseppe Caracciolo;Arash Kheradvar;Jagat Narula;Partho P. Sengupta - 通讯作者:
Partho P. Sengupta
Transvalvular flow
跨瓣流
- DOI:
10.1016/b978-0-12-814661-3.00009-5 - 发表时间:
2019 - 期刊:
- 影响因子:0
- 作者:
Daisuke Morisawa;Arash Kheradvar - 通讯作者:
Arash Kheradvar
The Current Landscape of Artificial Intelligence in Imaging for Transcatheter Aortic Valve Replacement
- DOI:
10.1007/s40134-024-00431-w - 发表时间:
2024-10-10 - 期刊:
- 影响因子:1.900
- 作者:
Shawn Sun;Leslie Yeh;Amir Imanzadeh;Soheil Kooraki;Arash Kheradvar;Arash Bedayat - 通讯作者:
Arash Bedayat
Arash Kheradvar的其他文献
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