Characterization of organ wasting/cachexia mechanisms

项目摘要 癌症恶病质是一种毁灭性的综合征，其原因是周围组织因 肿瘤与远处组织之间的病理生理相互作用。尽管约80%的癌症患者 由恶病质引起，并与癌症患者约25%的死亡有关，目前尚无经批准的治疗方法 来对抗这种致命的疾病。癌症恶病质治疗进展有限的部分原因是我们 对肿瘤如何通过长时间诱导恶病质的潜在分子机制知之甚少. 范围交互作用。在我的博士后研究期间，我提出了一些研究，这些研究将提供 ImpL2和其他肿瘤分泌因子如何调节器官的机械洞察力 浪费。在Aim1中，我将剖析哪些致癌途径调节ImpL2。在目标2中，我将使用有针对性的 DAMID技术识别影响远端组织内稳的其他肿瘤衍生因子 器官萎缩。最后，在目标3中，我将探索导致器官浪费的其他条件是否与 ImpL2依赖的信号转导。总而言之，这些研究将确定调控网络协调器官 在病理条件下的消瘦，也为器官的潜在治疗靶点提供了新的见解 浪费。

Project Summary Cancer cachexia is a devastating syndrome resulting from the wasting of peripheral tissues as a result of pathophysiological interactions between tumors and distant tissues. Although ~80% of cancer patients suffer from cachexia and has been implicated in ~25% of death in cancer patients, there is no approved therapeutics to combat this deadly disease. Part of the reasons for limited progress in cancer cachexia is because we know little about the underlying molecular mechanisms on how tumor induces cachexia through long- range interactions. During my postdoctoral studies, I propose a number of studies that will provide mechanistic insights into how ImpL2 and other tumor-secreted factors are regulated to modulate organ wasting. In Aim1, I will dissect which tumorigenic pathways regulate ImpL2. In Aim 2, I will utilize targeted DamID technique to identify other tumor-derived factors that affect distant tissue homeostasis relevant for organ wasting. Finally, in Aim 3, I will explore whether other conditions that induce organ wasting interact with ImpL2-dependent signaling. Together, these studies will identify regulatory networks orchestrating organ wasting in pathological conditions and also provide novel insights into potential therapeutic targets for organ wasting.