Genetic determinants of thoracic aortic stiffness and remodeling

胸主动脉僵硬度和重塑的遗传决定因素

• 批准号: 10539295
• 负责人: JULIO ALONSO CHIRINOS MEDINA
• 金额: $ 19.5万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10539295
• 关键词: Acceleration; Address; Adoption; Adult; Age; Aging; Aorta; Aortic Segment; Award; Biological; Clinical; Clinical Investigator; Clinical Sciences; Collaborations; Data; Dedications; Deposition; Development; Diameter; Distal; Doctor of Philosophy; EFRAC; Echocardiography; Elasticity; Elastin; Electrocardiogram; Enrollment; Environment; Epidemiology; Equation; Equipment; Exhibits; Faculty; Femur; Fibrosis; Generations; Genetic Determinism; Genetic study; Genomics; Goals; Health; Heart failure; Heritability; Human; Image; Individual; Institution; K-Series Research Career Programs; Leadership; Left; Length; Location; Magnetic Resonance Imaging; Measurement; Measures; Medicine; Mendelian randomization; Mentors; Mentorship; Methodology; Methods; Muscle; Participant; Pathologic Processes; Patients; Pennsylvania; Phenotype; Physicians; Physiologic pulse; Play; Population; Population Study; Prevention approach; Process; Productivity; Professional Organizations; Research; Research Personnel; Resources; Respiratory Diaphragm; Rest; Role; Sample Size; Science; Scientist; Site; Surface; System; Thoracic aorta; Time; Training; Training Support; Translational Research; Universities; Ventricular; Work; age related; aging population; aortic valve; arterial tonometry; ascending aorta; biobank; burden of illness; calcification; career; career development; clinical imaging; clinical practice; deep learning; electric impedance; epidemiology study; exome; experience; genome wide association study; genomic data; hemodynamics; imaging study; improved; infancy; innovation; insight; interest; large datasets; medical schools; meetings; mid-career faculty; multidisciplinary; next generation; next generation sequencing; novel; patient oriented; patient oriented research; preservation; programs; prospective; research and development; research study; skills; success; time use; translational study; ultrasound

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.

项目摘要/摘要 这是胡里奥·奇里诺斯医学博士为患者导向研究(POR)颁发的K24指导奖的申请书。 博士，宾夕法尼亚大学佩雷尔曼医学院医学副教授 (宾夕法尼亚)。奇里诺斯博士的长期目标是：(1)大大促进我们对以下问题的理解和方法 预防和治疗主动脉老化及其相关疾病负担；(2)指导下一步 一代研究人员对主动脉老化的流行病学及其对人类健康的影响感兴趣。 这个职业中期发展奖将是帮助他通过专门的/受保护的时间实现这些目标的关键 用于指导活动，研究和开发新技能，预计将极大地提高 申请人在整个职业生涯中对这一领域的影响，以及他的学员的影响和成功。 这位候选人在导师、领导力和研究效率方面都有很好的记录。他的研究计划 包括关于动脉老化及其在心力衰竭中的作用的流行病学、转化性和POR研究 保存射血分数(HFpEF)和其他困扰我们老龄化人口的条件。的科学目标 本研究旨在研究与年龄相关的胸主动脉僵硬和延长的遗传决定因素。 使用大量可用的生物库以及相关的基因组和主动脉成像数据。其中包括英国生物库 以及宾夕法尼亚医学生物库。这些项目将包括应用一种新的方法来量化 主动脉脉搏波速度首次可在广泛应用的临床影像中回溯应用 学习。深入学习高通量的主动脉表型将在这项研究中发挥重要作用。这个 此应用程序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员的培训 在动脉老化中进行POR。本申请的职业发展目标是支持应聘者的 老龄化POR研究的专业发展和新技能的获得，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，以实现准确的高吞吐量 主动脉老化的表型分析。这将通过正式的培训课程和参与持续的 与专家在这些主题上的协作体验。应聘者还将从事职业发展 并通过召开关于动脉老化研究的科学会议促进动脉老化研究 通过现有的专业学会完善动脉老化POR研究的国家网络。这个 宾夕法尼亚州立大学临床和转化科学的机构环境非常出色。美国商务部 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，以 候选人作为一名以患者为导向的研究人员持续取得成功，负责培训新一代 在年长参与者中进行研究的初级调查人员。