Genetic determinants of thoracic aortic stiffness and remodeling

项目总结/摘要 这是Julio Chirinos博士为面向患者的研究（POR）申请K24指导奖， 宾夕法尼亚大学佩雷尔曼医学院医学博士、副教授 （佩恩）。Chirinos博士的长期目标是：（1）为我们的理解和方法做出实质性贡献， 预防和治疗主动脉老化及其相关疾病负担，以及;（2）指导下一个 一代对主动脉老化的流行病学及其对人类健康的影响感兴趣的研究者。 这个职业生涯中期发展奖对于帮助他通过专用/受保护的时间实现这些目标至关重要 指导活动，研究和开发新的技能，预计将大大提高 申请人在其职业生涯中对该领域的影响，以及他的学员的影响和成功。 候选人有很强的指导，领导和研究生产力的记录。他的研究计划 包括动脉老化及其在心力衰竭中的作用的流行病学、转化和POR研究， 保留射血分数（HFpEF）和其他困扰我们老龄化人口的疾病。的科学目标 本研究旨在探讨与年龄相关的胸主动脉硬化和延长的遗传决定因素 使用具有相关基因组和主动脉成像数据的大型可用生物库。其中包括英国生物银行 和宾州医学生物库这些项目将包括应用一种新的方法， 主动脉脉搏波速度，首次可在广泛可用的临床成像中回顾性应用 问题研究高通量主动脉表型的深度学习将在这项研究中发挥重要作用。的 本申请的指导目标是参与和支持宾夕法尼亚大学研究员和初级教师的培训， 在动脉老化中进行POR。此申请的职业发展目标是支持候选人的 专业发展和获取新技能的POR研究在老龄化，特别是：（1）基因组学 （全基因组关联研究，下一代测序和孟德尔随机化）;（2）应用 深度学习，利用大量成像数据，以实现准确的高通量 主动脉老化的表型。这将通过正规培训课程和参与持续的 与这些领域的专家合作。候选人还将从事职业发展 通过召开关于主动脉老化研究的科学会议，促进动脉老化研究， 通过现有的专业协会，改善动脉老化POR研究的国家网络。的 宾夕法尼亚大学临床和转化科学的机构环境是杰出的。部 宾夕法尼亚大学的医学已经做出了实质性的承诺，包括保护时间和专用空间， 候选人作为一个以病人为导向的研究人员，负责培养新一代的 在老年参与者中进行研究的初级研究人员。

Project Summary / Abstract This is an application for a K24 mentoring award for patient-oriented research (POR) from Julio Chirinos, MD, PhD, Associate Professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania (Penn). Dr. Chirinos‘ long-term goals are to: (1) Substantially contribute to our understanding and approaches to the prevention and treatment of aortic aging and its associated disease burden, and; (2) to mentor the next generation of investigators interested in the epidemiology of aortic aging and its consequences in human health. This mid-career development award will be critical to help him achieve these goals via dedicated/protected time for mentoring activities, research and development of new skills that are anticipated to greatly enhance the applicant’s impact in this field throughout the rest of his career, as well as the impact and success of his trainees. The candidate has a strong record of mentorship, leadership, and research productivity. His research program encompasses epidemiologic, translational and POR studies of arterial aging and its role in Heart Failure with Preserved Ejection Fraction (HFpEF) and other conditions that afflict our aging population. The scientific goal of this proposal is to investigate the genetic determinants of age-related thoracic aortic stiffening and elongation using large available biobanks with associated genomic and aortic imaging data. These include the UK Biobank and the Penn Medicine Biobank. The projects will include the application of a novel method for quantification of aortic pulse wave velocity that can, for the first time, be applied retrospectively in widely available clinical imaging studies. Deep learning for high-throughput aortic phenotyping will play an important role in this research. The mentoring goals of this application are to engage and support the training of Penn fellows and junior faculty to conduct POR in arterial aging. The career development goal of this application is to support the candidate’s professional development and acquisition of new skills for POR research in aging, specifically: (1) genomics (genome-wide association studies, next generation sequencing, and Mendelian Randomization); (2) Applied deep learning to leverage large banks of imaging data in order to accomplish accurate high-throughput phenotyping of aortic aging. This will be achieved through formal training courses and engaging in sustained collaboration experiences with experts in these topics. The candidate will also engage in career development and promotion of arterial aging research through convening scientific meetings on aortic aging research and improving the national network of POR research in arterial aging through existing professional societies. The institutional environment for clinical and translational science at Penn is outstanding. The Department of Medicine at Penn has made a substantial commitment, including protected time and dedicated space, toward the candidate’s sustained success as a patient-oriented researcher responsible for training a new generation of junior investigators who conduct research in older participants.