Identification of TGF-B regulated angiogenesis genes

描述(申请人提供)：血管生成是一个高度复杂和有序的过程，新的血管是由先前存在的血管形成的。血管生成对于正常组织的发育和维持，以及包括癌症在内的许多人类疾病的进展都是至关重要的。由于许多疾病的进展需要血管生成来支持，因此人们认为阻止血管生成有可能最大限度地减少疾病的进展。转化生长因子-β被认为是正常和异常血管生成的强大调节因子，但转化生长因子-β调控血管生成的分子机制尚不清楚。这项建议中的实验旨在检验这样一个假设，即转化生长因子-B信号调节正常血管形成所需基因的表达，而这些基因反过来又调节新血管形成的关键步骤。在验证这一假说时，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的转化生长因子-β调控基因；(3)根据识别的基因在正常血管形成的关键步骤中的作用来确定已识别的基因。为了实现这些目标，我们将发现和表征新的基因，这些基因对于控制血管生成非常重要，因此有一天可能被用作小分子的分子靶点，旨在减缓或阻止血管生成，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.