Activation mechanisms of the Hypoxia Inducible Factor-1a (HIF-1a) and the HIF-Like-Factor

氧气的持续供应对人体的正常功能是必不可少的。当氧气水平变得有限时，身体试图通过增加携带氧气的红细胞的数量和促进新血管的发育以增加组织的血液供应来纠正这种情况。细胞还通过改变其内部生物化学和代谢来适应，以减少能量需求。这些变化是细胞内基因重编程的结果。一个主要的问题是细胞如何感觉到它们处于低氧环境中，以及它们通过什么机制启动基因重编程。我们正在研究两种蛋白质，当细胞受到缺氧（低氧）胁迫时，它们能够改变基因的活性，并试图发现蛋白质如何响应缺氧从潜伏形式转变为活性形式。更深入地了解细胞缺氧反应中涉及的分子机制，对于开发新的治疗方法来治疗涉及氧流中断的疾病状态（例如心脏病发作和中风）非常重要。阻断缺氧诱导的血管发育的药物在癌症治疗中也可能是非常有益的，因为阻断肿瘤生长的血液供应可能导致肿瘤饥饿和萎缩。

A continual supply of oxygen is essential for normal functioning of the human body. When oxygen levels become limiting, the body attempts to rectify the situation by increasing the number of oxygen carrying red blood cells and promoting development of new blood vessels to increase the blood supply to tissues. Cells also adapt by altering their internal biochemistry and metabolism to decrease energy needs. These changes are the result of a genetic reprogramming within the cells. A major question is how the cells sense they are in a low oxygen environment and by what mechanisms they initiate genetic reprogramming. We are studying two proteins which have the ability to alter activity of genes when cells are stressed by hypoxia (low oxygen), and seek to discover how the proteins switch from latent forms to active forms in response to hypoxia. A greater understanding of the molecular mechanisms involved in the cellular hypoxic response is important to the development of new therapeutics for disease states involving disrupted oxygen flow (eg heart attack and stroke). Drugs which would block the hypoxic induced development of blood vessels could also be extremely beneficial in cancer treatment, as blocking blood supply to growing tumours can result in their starvation and shrinkage.