Multiscale mechanobiology of right ventricular failure

与左心室衰竭（LVF）相比，人们对右心室衰竭（RVF）知之甚少。 严重后果是不存在治疗方法。家长补助金将追求具体目标，以确定 RVF 的多尺度机制，采用数据驱动、多尺度计算建模方法。在这里我们 提出补充目标以调查免疫系统对裂谷热的贡献。实验和 开发计算模型组件，该组件将纳入母公司资助的多尺度项目中 方法，将增进我们对驱动 RVF 的多尺度机制的理解。 总体目标是 Bermudez 先生，他是一名数学、计算和系统生物学研究生 开发一种新颖的多尺度免疫模型，完善母基金的多尺度建模方法 由于压力超负荷而导致 RVF 进展。在补充目标 1 中，Bermudez 先生将确定影响 由于压力超负荷引起的心肌细胞线粒体活性氧增加 巨噬细胞极性和激活功能障碍。在补充目标 2 中，Bermudez 先生将衡量并 模拟巨噬细胞激活对压力引起的右心室纤维化重塑的影响 超载。此外，Bermudez 先生还将获得切斯勒研究所几位资深科学家的专业知识和指导。 实验室拥有丰富的生物工程和计算建模经验。 在该项目期间，Bermudez 先生将获得生物医学工程方面的新的宝贵技能， 计算模型构建、计算模型验证以及所需的任何实验技能 进行必要的实验来测量关键的免疫学变量。贝穆德斯先生将 准备一份季度内部指导工作表，类似于个人发展计划（IDP） 与切斯勒博士合作，参加加州大学尔湾分校 (UCI) 的研究和写作成功研讨会，参加全国 会议展示他的工作，指导本科生在切斯勒实验室进行研究，并继续 他作为创始成员参与了研究生项目的多元化、公平和包容性委员会。 UCI为完成该研究项目和继续专业提供了良好的环境 Jose Bermudez 先生的发展。此外，Bermudez 先生将在 Edwards Lifesciences 工作 基金会心血管创新与研究中心 (CIRC) 社区并利用其 许多社交和学习机会。总之，这些研究和培训活动相结合 旨在帮助 Bermudez 先生在研究生期间继续在学术研究方面取得蓬勃发展。

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.