Mitochondrial regulation in cardiovascular and cancer biology

我们正专注于影响心血管运动能力的线粒体功能的调节，以及对肿瘤发生的影响。我们已经证明，P53通过对线粒体功能的正向调节来平衡呼吸和糖酵解产生的能量，并促进有氧代谢。这种生物学机制的一个有趣的效果是，P53基因缺陷的小鼠在有氧运动能力方面表现出严重的缺陷，揭示了一个已被充分研究的肿瘤抑制基因的新功能，该基因主要与细胞周期和基因组调节有关。我们正在进一步确定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。具体地说，我们正在使用临床和基础研究来研究Li-Fraumeni综合征患者的代谢功能，Li-Fraumeni综合征是一种由p53基因胚系突变引起的早癌综合征。这项研究的目标是获得基本的见解，这些见解可能有助于开发新的战略，以预防特定人群的癌症，如Li-Fraumeni综合征，并改善一般人类健康。

We are focusing on the regulation of mitochondrial function that impacts cardiovascular exercise capacity with implications for tumorigenesis. We have shown that p53 balances the energy generated by respiration and glycolysis and promotes aerobic metabolism through it positive regulation of mitochondrial function. An interesting effect of this biological mechanism is that mice deficient in p53 display profound deficiencies in aerobic exercise capacity, revealing a new function for a well-studied tumor suppressor 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. Specifically, we are studying metabolic functions using both clinical and basic studies in individuals with Li-Fraumeni syndrome, a premature cancer syndrome caused by germline mutations in the p53 gene. The goal of this research is to derive basic insights that may help in the development of new strategies for preventing cancer in specific populations such as in Li-Fraumeni syndrome and also for improving general human health.