Multiscale mechanobiology of right ventricular failure

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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.