Hedgehog signaling and signal transduction

描述（由申请人提供）：刺猬信号传导与许多癌症有关，并已被证明是抗癌治疗的有用靶点。之前的工作，包括我的实验室的重要贡献，已经确定了刺猬蛋白是动物发育的主要调节因子之一，在无脊椎动物和脊椎动物的大多数组织和器官中起着关键作用。使用新开发的试剂和方法，开辟了研究Hh信号的新途径，本应用程序中提出的工作将确定和表征Hh产生细胞用于制备和传递Hh蛋白的过程，Hh接收细胞用于准备和处理其到达的过程，以及调节负责Hh通路输出的转录因子Ci的形式和活性的过程。这些问题对于理解如何开发新的和更好的控制Hh活性的治疗方案至关重要。

DESCRIPTION (provided by applicant): Hedgehog signaling has been implicated in many cancers and has been shown to be a useful target for anti-cancer therapy. Previous work, including key contributions from my lab, have established that the Hedgehog protein is one of the major regulators of animal development, playing key roles in most tissues and organs in both invertebrates and vertebrates. Using newly developed reagents and methods that open new ways to study Hh signaling, the work proposed in this application will identify and characterize the processes that Hh-producing cells use to prepare and deliver Hh protein, the processes that Hh-receiving cells use to prepare for and handle its arrival, and the processes that regulate the form and activity of Ci, the transcription factor that is responsible for Hh pathway output. These issues are critical to understanding how new and better therapeutic regimens controlling Hh activity can be developed.