DPC4 function in human pancreatic cancer

DPC4 在人类胰腺癌中的功能

• 批准号: 7115721
• 负责人: Gloria Huei-Ting Su
• 金额: $ 15.55万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-27 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7115721
• 关键词: biological signal transduction; disease /disorder model; gene mutation; genetically modified animals; immunocytochemistry; laboratory mouse; model design /development; neoplasm /cancer genetics; neoplastic process; pancreas neoplasms; reporter genes; transforming growth factors; tumor suppressor genes

DESCRIPTION (provided by applicant): Dr. Gloria H. Su received her Ph.D. from the University of Chicago. During which, she acquired expertise in the development and analysis of knock-out mice in the laboratory of Dr. M. Celeste Simon. In her postdoctoral training in the molecular genetics laboratory of Dr. Scott E. Kern at The Johns Hopkins University, she identified several tumor suppressor genes important to human pancreatic and biliary adenocarcinomas. She joined the faculty at The Johns Hopkins University in July 2000 in the Department of Pathology, and has since combined her two areas of expertise to focus on the development of mouse models for human pancreatic cancer. Most patients with pancreatic cancer are diagnosed at an advanced stage and the current available treatments are not effective in prolonging the patients' survival. New approaches for early diagnoses and treatment could be extensively studied in animal models, if one were available. The continued discoveries of tumor suppressor genes important in pancreatic cancer have now rendered it possible to construct an animal model to further our understanding of pancreatic tumorigenesis. Creating mouse models that mirror human pancreatic tumorigenesis using knock-out and transgenic techniques is one of Dr. Su's major goals. Here she proposes to study the in vivo impact of a tumor-suppressor gene, DPC4 (SMAD4/MADH4), important for human pancreatic cancer, using conditional knock-out mice and a transgenic mouse line carrying DPC4-specific reporter gene. Dr. Su's position at The Johns Hopkins University will provide her access to important resources such as the Transgenic Mouse Core Laboratory, and the intellectual support of a large group of scientists and clinicians dedicated to curing pancreatic cancer. Among them are her sponsors, Drs. Scott E. Kern and Steven D. Leach, who are internationally recognized researchers in the field of pancreatic cancer. From her sponsors, she will continue to gain valuable lessons on the human genetics, pathology of pancreatic cancer, and murine pancreatic development. The clinical backgrounds and focus of her mentors will also assist Dr. Su in framing her research effort so that they remain directly relevant to human pancreatic cancer. With the enormous support of her mentors, colleagues, and the Department of Pathology, Dr. Su will be able to conduct her research in the richest intellectual and resourceful environment possible for academic and research career development.

简介(申请人提供)：苏慧兰博士毕业于 芝加哥大学。在此期间，她获得了 M·塞莱斯特博士实验室中基因敲除小鼠的培育与分析 西蒙。在她的分子遗传学实验室的博士后培训中 约翰·霍普金斯大学的斯科特·E·克恩博士，她发现了几个 肿瘤抑制基因对人类胰腺和胆管的重要作用 腺癌。年，她加入了约翰·霍普金斯大学的教职 2000年7月在病理学系就读，此后将她的两个领域结合在一起 专注于人类胰腺小鼠模型的开发 癌症。大多数胰腺癌患者被诊断为晚期 目前可用的治疗方法并不能有效地延长 病人的生存。早期诊断和治疗的新方法可能是 在动物模型中进行了广泛的研究，如果有的话。接下来的 胰腺癌重要抑癌基因的发现 使得构建一个动物模型来加深我们对 胰腺肿瘤的发生。创建模仿人类的老鼠模型 使用基因敲除和转基因技术的胰腺肿瘤发生是 苏博士的主要目标。在这里，她提议研究一种病毒在体内的影响 肿瘤抑制基因DPC4(Smad4/MADH4)对人胰腺的重要作用 癌症，使用条件基因敲除小鼠和携带 DPC4特异性报告基因。苏博士在约翰·霍普金斯大学的职位 大学将为她提供访问重要资源的途径，如 转基因小鼠的核心实验室，和一个大的智力支持 致力于治疗胰腺癌的科学家和临床医生小组。 其中包括她的赞助商斯科特·E·科恩博士和史蒂文·D·利奇博士，他们是 国际公认的胰腺癌领域的研究人员。 从她的赞助商那里，她将继续获得关于人类的宝贵经验 胰腺癌的遗传学、病理学和小鼠胰腺发育。 她的导师的临床背景和重点也将帮助苏医生 制定她的研究成果，使其与人类保持直接相关 胰腺癌。在她的导师、同事和 病理学系，苏博士将能够在 最丰富的智力和足智多谋的环境为学术和 研究事业发展。

项目成果

Loss of Activin Receptor Type 1B Accelerates Development of Intraductal Papillary Mucinous Neoplasms in Mice With Activated KRAS.

• DOI: 10.1053/j.gastro.2015.09.013
• 发表时间: 2016-01
• 期刊: Gastroenterology
• 影响因子: 29.4
• 作者: Qiu W;Tang SM;Lee S;Turk AT;Sireci AN;Qiu A;Rose C;Xie C;Kitajewski J;Wen HJ;Crawford HC;Sims PA;Hruban RH;Remotti HE;Su GH
• 通讯作者: Su GH

PIK3CA, KRAS, and BRAF mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/C) of the pancreas.

胰腺导管内乳头状粘液性肿瘤/癌 (IPMN/C) 中的 PIK3CA、KRAS 和 BRAF 突变。

• DOI: 10.1007/s00423-008-0285-7
• 发表时间: 2008
• 期刊: Langenbeck's archives of surgery
• 作者: Schönleben,Frank;Qiu,Wanglong;Remotti,HelenE;Hohenberger,Werner;Su,GloriaH
• 通讯作者: Su,GloriaH

BRAF and KRAS gene mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) of the pancreas.

• DOI: 10.1016/j.canlet.2006.09.007
• 发表时间: 2007-05
• 期刊: Cancer letters
• 影响因子: 9.7
• 作者: F. Schönleben;Wanglong Qiu;Karl C. Bruckman;N. Ciau;Xiaojun Li;Margaret H. Lauerman;H. Frucht;J. Chabot;J. Allendorf;H. Remotti;G. Su

Disruption of p16 and activation of Kras in pancreas increase ductal adenocarcinoma formation and metastasis in vivo.

• DOI: 10.18632/oncotarget.357
• 发表时间: 2011-11
• 期刊: Oncotarget
• 作者: Qiu W;Sahin F;Iacobuzio-Donahue CA;Garcia-Carracedo D;Wang WM;Kuo CY;Chen D;Arking DE;Lowy AM;Hruban RH;Remotti HE;Su GH
• 通讯作者: Su GH

Smad4 loss synergizes with TGFα overexpression in promoting pancreatic metaplasia, PanIN development, and fibrosis.

• DOI: 10.1371/journal.pone.0120851
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Garcia-Carracedo D;Yu CC;Akhavan N;Fine SA;Schönleben F;Maehara N;Karg DC;Xie C;Qiu W;Fine RL;Remotti HE;Su GH
• 通讯作者: Su GH