Multiscale mechanobiology of right ventricular failure

与左心室衰竭（LVF）相比，对右心室衰竭（RVF）的了解很少， 严重后果是没有治疗方法。父母补助金将追求具体目标，以确定 用数据驱动的多尺度计算建模方法研究裂谷热的多尺度机制。这里我们 建议补充调查免疫系统对裂谷热的作用。实验和 开发一个计算模型组件，该组件将被纳入父母补助金的多尺度 这一方法将促进我们对裂谷热多尺度驱动机制的理解。 总体目标是为Mr.Mr.Mr.Mr.Mr.Mr.Mr.Mr.Mr.Mr.Mr. 开发一种新的多尺度免疫模型，该模型改进了Parent Grant的多尺度建模方法， 由于压力超负荷导致RVF进展。在补充目标1中，贝莱德斯先生将确定 增加活性氧，由于压力超负荷诱导心肌细胞线粒体 功能障碍，对巨噬细胞极性和活化的影响。在补充目标2中，Mr. Pandez将衡量和 建立巨噬细胞活化对压力所致右心室纤维化重构的影响的模型 超载。此外，Chesler公司的几位资深科学家将为Mr.Kendez提供专业知识和指导。 拥有丰富的生物工程和计算建模经验。 在这个项目期间，Mr. Alberdez将获得生物医学工程方面的新的和宝贵的技能， 计算模型构建，计算模型验证，以及所需的任何实验技能 进行必要的实验以测量关键的免疫学变量。Mr. Alberdez将 准备季度内部指导工作表，类似于个人发展计划（IDP）， 与Chesler博士一起，参加UCI的研究和写作成功研讨会，参加国家 会议，介绍他的工作，指导本科生进行研究在切斯勒实验室，并继续 他在他的研究生课程的多样性，公平和包容性委员会的参与，作为创始成员。 UCI为完成该研究项目和继续专业提供了良好的环境 何塞·罗德里格斯先生的发展。此外，Mr. Pandez将在Edwards Lifesciences工作。 基金会心血管创新和研究中心（CIRC）社区，并利用他们的 许多网络和学习机会。总之，这些研究和培训活动是 旨在为Mr. Alberdez在研究生阶段继续从事学术研究做好准备。

In comparison to left ventricular failure (LVF), right ventricular failure (RVF) is poorly understood with the critical consequence that no therapies exist. The parent grant will pursue Specific Aims to determine the multiscale mechanisms of RVF with a data-driven, multiscale, computational modeling approach. Here we propose supplemental aims to investigate immune system contributions to RVF. The experiments and development of a computational model component, which will be incorporated into the parent grant’s multiscale approach, will advance our understanding of the multiscale mechanisms that drive RVF. The overall goal is for Mr. Bermudez, a graduate student in Mathematical, Computational and Systems Biology to develop a novel multiscale immune model that refines the parent grant’s multiscale modeling approach of RVF progression due to pressure overload. In Supplemental Aim 1, Mr. Bermudez will determine the impact of increased reactive oxygen species, due to pressure overload-induced cardiomyocyte mitochondrial dysfunction, on macrophage polarity and activation. In Supplemental Aim 2, Mr. Bermudez will measure and model the impact of macrophage activation on fibrotic remodeling of the right ventricle due to pressure overload. Also, Mr. Bermudez will receive expertise and mentoring from several senior scientist in the Chesler lab with extensive bioengineering and computational modeling experience. During the period of this project, Mr. Bermudez will gain new and valuable skills in biomedical engineering, computational model construction, computational model validation, and any experimental skills required to conduct the necessary experimentation to measure the key immunological variables. Mr. Bermudez will prepare a quarterly in-house mentoring worksheet, similar to an Individual development Plan (IDP) in conjunction with Dr. Chesler, participate in workshops for research and writing success at UCI, attend national conferences to present his work, mentor undergraduates conducting research in the Chesler Lab, and continue his participation in his graduate program’s Diversity, Equity and Inclusion Committee, as a founding member. UCI provides an excellent environment for the completion of this research project and continued professional development of Mr. Jose Bermudez. Furthermore, Mr. Bermudez will work within the Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center (CIRC) community and take advantage of their many networking and learning opportunities. In all, these combined research and training activities are designed to prepare Mr. Bermudez for continued thriving in academic research in his post-graduate years.