Identification of TGF-B regulated angiogenesis genes

描述（由申请人提供）：血管生成是一个高度复杂和有序的过程，其中新血管由预先存在的血管形成。血管生成对于正常组织的发育和维持以及对于包括癌症在内的许多人类疾病的进展至关重要。由于血管生成是支持许多疾病的晚期进展所必需的，因此认为停止血管生成具有使疾病进展最小化的潜力。TGF-β被认为是正常和异常血管生成的有力调节剂，但TGF-β调节血管生成的分子机制在很大程度上是未知的。该提案中的实验旨在验证以下假设：TGF-β信号调节适当血管形成所需的基因表达，并且这些基因反过来调节新血管形成的关键步骤。在验证这一假设时，我们的目标是：（1）发现参与血管生成过程的新基因;（2）发现参与血管生成过程的新TGF-β调节基因;（3）基于其对适当血管生成的基本步骤的影响来表征所鉴定的基因。在实现这些目标的过程中，我们将发现和表征对控制血管生成很重要的新基因，因此有一天可能被用作小分子的分子靶点，这些小分子被设计用于减缓或停止血管生成，从而改善癌症患者的临床结果。

DESCRIPTION (provided by applicant): Angiogenesis is a highly complex and ordered process whereby new blood vessels are formed from preexisting blood vessels. Angiogenesis is critically important for the development and maintenance of normal tissues, and for the progression of many human diseases including cancer. Because angiogenesis is required to support advanced progression of many diseases, it is thought that halting angiogenesis holds potential for minimizing disease progression. TGF-B is believed to be a powerful regulator of normal and abnormal angiogenesis, but the molecular mechanisms by which TGF-B regulates angiogenesis are largely unknown. The experiments in this proposal are designed to test the hypothesis that TGF-B signaling regulates the expression of genes required for proper blood vessel formation, and that these genes in turn regulate key steps in new blood vessel formation. In testing this hypothesis, we aim to (1) discover novel genes involved in the process of angiogenesis; (2) discover novel TGF-B regulated genes involved in the process of angiogenesis; and (3) characterize identified genes based on their effects on essential steps for proper angiogenesis. In meeting these aims we will discover and characterize novel genes which are important for controlling angiogenesis and may therefore one day, be used as molecular targets for small molecules designed to slow or halt angiogenesis thus improving clinical outcomes for cancer patients.