Multiplexed Imaging of Energy Metabolism in Murine Models of Heart Failure

心力衰竭小鼠模型能量代谢的多重成像

基本信息

  • 批准号:
    9096879
  • 负责人:
  • 金额:
    $ 16.42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-03-10 至 2019-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): This proposal describes a five-year career development and training plan for Dr. Marcello Panagia, a physician-scientist, who at the time of the award will have completed training in Cardiovascular Medicine and Advanced Cardiac Imaging (MR/CT/PET) at Massachusetts General Hospital (MGH). Under the mentorship of Dr. David Sosnovik and Dr. Robert Gerszten, Dr. Panagia is now embarking on a cutting-edge research plan that combines his background in cardiac energy metabolism with advanced imaging technologies. His career development plan, that leverages the extensive resources offered by MGH, brings together a robust team of investigators with expertise in molecular imaging, metabolomics, signal transduction and magnetic resonance imaging. During the period of funding, Dr. Panagia will have faculty positions in the Cardiology and Radiology Divisions at MGH as well as a faculty appointment at Harvard Medical School. His ultimate goal is to become an independent investigator studying energy metabolism with a sophisticated tool-kit of imaging technologies. Receipt of this award will allow Dr. Panagia to obtain additional training in optical imaging, magnetic resonance imaging and spectroscopy, metabolomics, biostatistics, research design and ethics, and will facilitate his transition to research independence. In addition to providing a mechanism for further training, the award will allow Dr. Panagia to continue studies in the dysregulation of energy metabolism in heart failure. Heart failure is a leading cause of morbidity and mortality in the United States and the dysregulation of energy metabolism is a fundamental feature of its pathogenesis. However, the capacity to adequately study the processes involved in energy metabolism could be significantly improved. Although valuable, current techniques are limited by their complexity, relatively low throughput, and inability to image multiple processes at the same time. Dr. Panagia hypothesizes that a novel optical approach can permit the simultaneous imaging of multiple metabolic and energetic pathways in the heart and peripheral tissues and provide important insights into heart failure pathogenesis. Dr. Panagia has obtained preliminary results that show the feasibility of this approach in a coronary ligation model of heart failure. He has shown that Cerenkov luminescence using 18F- fluorodeoxyglucose in this model clearly differentiates viable myocardium from scar and that simultaneous imaging with mitochondrial-targeted probes provides valuable time-coherent and spatially coherent information. This optical approach will be enhanced by the use of non-invasive measures of metabolic activity, such as peripheral tissue oxygen consumption by magnetic resonance imaging, as well as high-throughput screening of blood and tissue metabolites (metabolomics). Dr. Panagia proposes to extend the investigation to include multiple models of heart failure of different etiologies and to examine, in more detail, the energetic features that underlie the transition from compensated to decompensated heart failure. In summary, by bringing together cutting edge technology and a well-rounded team of experts in the context of a well-defined research plan and mentorship structure, Dr. Panagia will be able to synergistically merge the fields of advanced imaging and energy metabolism to elucidate novel mechanisms that underlie cardiac pathophysiology and elaborate the skills essential for him to become an independent investigator.
描述(由申请人提供):本提案描述了 Marcello Panagia 博士的五年职业发展和培训计划,Marcello Panagia 博士是一名医师兼科学家,获奖时他将在马萨诸塞州总医院 (MGH) 完成心血管医学和高级心脏成像 (MR/CT/PET) 培训。在 David Sosnovik 博士和 Robert Gerszten 博士的指导下,Panagia 博士目前正在着手一项尖端研究计划,将他在心脏能量代谢方面的背景与先进的成像技术相结合。他的职业发展计划利用了麻省总医院提供的广泛资源,汇集了一支强大的研究人员团队,他们在分子成像、代谢组学、信号转导和磁共振成像方面拥有专业知识。在资助期间,Panagia 博士将在麻省总医院心脏病学和放射科担任教职,并在哈佛医学院担任教职。他的最终目标是成为一名独立研究者,利用先进的成像技术工具包研究能量代谢。获得该奖项将使 Panagia 博士能够获得以下领域的额外培训: 光学成像、磁共振成像和光谱学、代谢组学、生物统计学、研究设计和伦理学,并将促进他向独立研究的过渡。除了提供进一步培训的机制外,该奖项还将允许 Panagia 博士继续研究心力衰竭中的能量代谢失调。心力衰竭是美国发病和死亡的主要原因,能量代谢失调是其发病机制的基本特征。然而,充分研究能量代谢过程的能力可以显着提高。尽管很有价值,但当前的技术因其复杂性、相对较低的吞吐量以及无法同时对多个进程进行成像而受到限制。 Panagia 博士推测,一种新颖的光学方法可以同时对心脏和外周组织中的多种代谢和能量途径进行成像,并为心力衰竭发病机制提供重要的见解。 Panagia 博士获得了初步结果,表明该方法在心力衰竭冠状动脉结扎模型中的可行性。他表明,在该模型中使用 18F-氟脱氧葡萄糖的切伦科夫发光可以清楚地区分存活的心肌和疤痕,并且使用线粒体靶向探针的同步成像提供了宝贵的时间相干和空间相干信息。这种光学方法将通过使用代谢活动的非侵入性测量来增强,例如通过磁共振成像检测外周组织耗氧量,以及血液和组织代谢物的高通量筛选(代谢组学)。 Panagia 博士建议将研究范围扩大到包括不同病因的多种心力衰竭模型,并更详细地检查: 从代偿性心力衰竭向失代偿性心力衰竭转变的能量特征。总之,通过在明确的研究计划和指导结构的背景下汇集尖端技术和全面的专家团队,Panagia 博士将能够协同融合先进成像和能量代谢领域,以阐明心脏病理生理学的新机制,并阐述他成为独立研究者所必需的技能。

项目成果

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Marcello Panagia其他文献

Marcello Panagia的其他文献

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{{ truncateString('Marcello Panagia', 18)}}的其他基金

Multiplexed Imaging of Energy Metabolism in Murine Models of Heart Failure
心力衰竭小鼠模型能量代谢的多重成像
  • 批准号:
    9330905
  • 财政年份:
    2016
  • 资助金额:
    $ 16.42万
  • 项目类别:
Multiplexed Imaging of Energy Metabolism in Murine Models of Heart Failure
心力衰竭小鼠模型能量代谢的多重成像
  • 批准号:
    8753247
  • 财政年份:
    2014
  • 资助金额:
    $ 16.42万
  • 项目类别:
Multiplexed Imaging of Energy Metabolism in Murine Models of Heart Failure
心力衰竭小鼠模型能量代谢的多重成像
  • 批准号:
    8920164
  • 财政年份:
    2014
  • 资助金额:
    $ 16.42万
  • 项目类别:

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