Genetic insights into mitochondrial function, cancer and cardiovascular diseases

对线粒体功能、癌症和心血管疾病的遗传学见解

• 批准号: 7969099
• 负责人: PAUL M. HWANG
• 金额: $ 163.84万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7969099
• 关键词: Aerobic Exercise; Atherosclerosis; Biology; Cardiovascular Diseases; Cardiovascular Physiology; Cell Cycle; Clinical Protocols; Clinical Research; Exercise; Genes; Genetic; Genetic Screening; Genomics; Glycolysis; Human; Inflammation; Li-Fraumeni Syndrome; Malignant Neoplasms; Mediating; Mitochondria; Molecular; Mus; Mutation; Pathway interactions; Patients; Regulation; Respiration; Sampling; TP53 gene; Translating; Tumor Suppressor Genes; energy balance; human subject; insight; mouse model; novel; translational study; tumorigenesis

We are focusing on a novel pathway that regulates mitochondrial function and cardiovascular exercise capacity with implications for tumorigenesis. We have shown that the tumor suppressor gene p53 balances the energy generated by respiration and glycolysis and that this effect is primarily mediated through its regulation of mitochondrial function. Interestingly, mice deficient in p53 display profound deficiencies in aerobic exercise capacity revealing a new function for a well-studied gene mainly associated with cell cycle and genomic regulation. We are further characterizing the biology underlying these observations and translating them to humans through clinical studies. We are also continuing our translational studies on inflammation and atherosclerosis that was initiated by the genetic screen of easily accessible patient samples.

我们正在关注调节线粒体功能和心血管运动能力与肿瘤发生的新途径。我们已经证明，肿瘤抑制基因p53平衡呼吸和糖酵解产生的能量，这种作用主要是通过其对线粒体功能的调节来介导的。有趣的是，缺乏p53的小鼠在有氧运动能力方面表现出严重的缺陷，这揭示了一个被充分研究的主要与细胞周期和基因组调控相关的基因的新功能。我们正在进一步描述这些观察结果背后的生物学特征，并通过临床研究将其转化为人类。我们还继续进行炎症和动脉粥样硬化的转化研究，这是由易于获取的患者样本的遗传筛选发起的。