Gene Targets of Wnt Signaling in Pancreatic Cancer

描述（由申请人提供）：候选人：申请人目前是 外科肿瘤学系外科助理教授， 辛辛那提大学。 在开始这第一个教师职位之前， 1996年8月，他是康奈尔大学医学中心的外科住院医生， 然后是医学博士的外科肿瘤学研究员安德森癌症中心。 洛伊医生 他坚定地致力于学术外科肿瘤学，他努力 无论是作为一个看护者还是作为一个研究者都很出色。 为此，他希望 继续他的基础研究培训在一个结构化的，指导的环境 带 目标是成为一名有效的独立调查员。 环境：本提案中概述的研究将由Dr. 乔安娜格罗登，分子遗传学系副教授， 生物化学和微生物学以及助理研究员， 霍华德休斯医学研究所。 格罗登博士是国际公认的 癌症遗传学和结肠腺瘤性息肉病研究专家 基因 格罗登博士和洛伊博士有着杰出的工作关系， 已经导致同行评审手稿的出版。 这将 是一个巨大的资产，在促进罗伊博士的进步，成为一个 独立科学家 辛辛那提大学是一所富有的大学， 一个工作、合作和学习的智力环境。 许多 医学院内有核心设施。 研究：胰腺 癌症仍然是几乎在所有情况下都是致命的常见疾病。 所述Wnt 信号通路在许多恶性肿瘤中被激活， 腺瘤性结肠息肉病（APC）或β-连环蛋白基因。 虽然APC没有 以前被认为是胰腺中重要的肿瘤抑制因子， 初步的工作表明，Wnt信号在这些细胞中经常被激活， 肿瘤的 本申请的目的是鉴定Wnt的靶基因 胰腺癌中的信号传导。 核心假设是异常的Wnt 信号传导在胰腺癌的一个子集中是活跃的， 胰腺导管癌的发生与特异性转录调控 靶基因 中心假设将通过追求三个测试 具体目标： 1)确定与Wnt相关的遗传改变 胰腺癌中的p通路激活，以确定其 与已知的临床和病理预后因素的关系; 2） 确定Wnt途径诱导的转录是否与 胰腺癌细胞的生长调控; 3）筛选Wnt的靶基因 胰腺癌细胞中的信号传导。 我们的长期目标是了解 这些基因如何促进胰腺癌的发生， 它们可以被调节用于治疗目的。

DESCRIPTION (provided by applicant): Candidate: The applicant is currently an Assistant Professor of Surgery in the Division of Surgical Oncology at the University of Cincinnati. Prior to starting this first faculty position in 8/96, he was a resident in surgery at Cornell University Medical Center and then a surgical oncology fellow at the M.D. Anderson Cancer Center. Dr. Lowy has a steadfast commitment to academic surgical oncology, and he strives to excel as both a caregiver and as a researcher. To this end, he would like to continue his basic research training in a structured, mentored environment w i t h the goal of becoming an effective, independent investigator. Environment: The research outlined in this proposal will be sponsored by Dr. Joanna Groden, an Associate Professor in the Department of Molecular Genetics, Biochemistry and Microbiology as well as an Assistant Investigator in the Howard Hughes Medical Institute. Dr. Groden is an internationally recognized expert in cancer genetics and in the study of the adenomatous polyposis coli gene. Dr. Groden and Dr. Lowy have an outstanding working relationship that has already resulted in publication of peer-reviewed manuscripts. This will be a tremendous asset in fostering Dr. Lowy's progress toward becoming an independent scientist. The University of Cincinnati is a rich and collegial intellectual environment in which to work, collaborate and study. Numerous core facilities are available within the Medical School. Research: Pancreatic cancer remains a common disease that is lethal in nearly all cases. The Wnt signaling pathway is activated in numerous malignancies by mutation of the adenomatous polyposis coli (APC) or beta-catenin genes. While APC has not previously been considered an important tumor suppressor in the pancreas, our preliminary work suggests that Wnt signaling is frequently activated in these tumors. The objective of this application is to identify target genes of Wnt signaling in pancreatic cancer. The central hypothesis is that aberrant Wnt signaling is active in a subset of pancreatic cancers and contributes to pancreatic duct carcinogenesis by transcriptional regulation of specific target genes. The central hypothesis will be tested by pursuing three specific aims: 1) To identify the genetic alterations associated with Wnt p a thway activation in pancreatic cancer in order to determine their relationship to known clinical and pathologic prognostic factors; 2) To determine whether Wnt pathway induced transcription is associated with loss of growth control in pancreatic cancer cells; 3) To identify target genes of Wnt signaling in pancreatic cancer cells. Our long-range goal is to understand how these genes contribute to pancreatic carcinogenesis with the hope that they can be modulated for therapeutic purposes.