MOLECULAR DETERMINANTS OF ANGIOGENSIS IN ORAL CANCER

描述：Lingen博士提出的职业发展计划包括多个 通过实验室的轮换与新的专业知识，这将直接 适用于他提出的研究工作。时间范围从1 一个月到3个月，地点从全国各地到 同一个机构。于第一年，彼已作出安排，前往探望陈博士。 Leroy Hood在华盛顿大学学习了一个月， 微阵列技术第二年，他将在 布莱恩·尼科洛夫博士在洛约拉大学的实验室， 在逆转录病毒和腺病毒开发方面的经验， 包含他感兴趣的基因在第三年，他提议进行为期三个月的轮换 通过卢西奥·米勒博士在洛约拉的实验室，以获得如何 鉴定关键转录因子并进行启动子分析。第四年，他 访问了芝加哥大学伊莱恩·富克斯博士的实验室， 3-一个月的时间，以产生转基因小鼠，其中表达的 转基因将在可诱导的内皮细胞特异性 启动子最终轮换尚未确定，但仍将可用 以便以后考虑所需的最新技术。除了 上述轮换，林根博士还计划参加和讲座 与研究伦理学相关的课程。 所描述的研究项目与Lingen博士目前的R01相同 这是经过同行审查和资助的赠款。具体目标是： 1)详细描述功能性视黄酸受体的特征 通过进行北方和西方免疫印迹， 印迹，并通过进行电迁移率变动测定，以确定 表达的受体的功能状态。 2)为了确定哪些表达的视黄酸受体负责 导致微血管内皮细胞变得对 通过使用受体选择性配体和通过引入 显性负性、野生型或嵌合型视黄酸受体 微血管内皮细胞 3)研究维甲酸介导的抑制体内血管生成， 将含有逆转录病毒载体的人微血管内皮细胞 驱动显性负性、野生型或嵌合型视黄酸受体进入小鼠 并观察它们并入新形成的血管中。

DESCRIPTION: Dr Lingen's proposed career development plan consists of multiple rotations through laboratories with novel expertise which will be directly applicable to his proposed research endeavors. The time frames range from 1 month to 3 months and the locations vary from across the country to within the same institution. During the first year, he has made arrangements to visit Dr. Leroy Hood at the University of Washington for 1 month and learn the cDNA microarray technology. During the second year, he will work within the laboratory of Dr. Brian Nickoloff at Loyola University to gain hands-on experience in the development of both retroviruses and adenoviruses that contain his genes of interest. During year 3, he proposes a 3-month rotation through Dr. Lucio Miele's laboratory at Loyola to gain knowledge of how to identify key transcription factors and perform promoter analyses. In year 4, he visits the laboratory of Dr. Elaine Fuchs at the University of Chicago for a 3-month period to generate transgenic mice in which the expression of the transgenes will be under the control of an inducible endothelial cell specific promoter. The final rotation has not been determined, but will remain available for later consideration of state-of-the-art techniques needed. In addition to the above mentioned rotations, Dr. Lingen also plans to participate and lecture in courses related to research ethics at Loyola University. The described research project is identical to the Dr. Lingen's current R01 grant which has been peer-reviewed and funded. The specific aims are: 1) To characterize in detail the profile of functional retinoic acid receptors expressed in microvascular endothelial cells by performing Northern and Western blots, and by performing electromobility shift assays to determine the functional status of the expressed receptors. 2) To determine which of the expressed retinoic acid receptors are responsible for causing microvascular endothelial cells to become refractory to inducers of angiogenesis by employing receptor selective ligands, and by introducing either dominant negative, wild-type or chimeric retinoic acid receptors into microvascular endothelial cells. 3) To study retinoic acid-mediated inhibition of in vivo angiogenesis by introducing human microvascular endothelial cells containing a retrovirally driven dominant negative, wild-type or chimeric retinoic receptors into mice and observing their incorporation into newly forming vessels.