Epigenetic markers involved in colorectal cancer recurrence and metastases

描述（由申请人提供）：这个指导职业奖概述了Ahuja博士在癌症生物学领域向科学独立过渡的五年培训计划。Ahuja博士建议扩大她的科学技能和知识，预计她将在本奖励期结束时获得独立调查员地位。Ahuja博士将继续与表观遗传学专家Baylin博士建立科学指导关系。她还将接受Leach博士的指导，Leach博士是胰腺发育生物学专家，也是一名外科医生，他将提供有价值的临床指导。她得到了她所在部门的全力支持，以保护她在获奖期间至少75%的时间。Ahuja博士在Baylin博士的实验室内拥有实验室和办公空间，并完全沉浸在研究环境中。该实验室位于癌症研究大楼， 约翰霍普金斯和有机会获得许多既定的科学家与环境，有利于合作和支持临床科学家。该研究计划的重点是了解DNA甲基化在结直肠癌转移和复发中的作用，并了解其作为翻译标记物的适用性。涉及启动子相关CpG岛异常DNA甲基化的表观遗传基因沉默是结直肠癌中肿瘤抑制基因失活的中心机制。我们假设甲基化谱作为结直肠癌复发的预后标志物具有巨大的潜力，并且甲基化谱可能允许结直肠癌的分子分期。为了验证这些假设，提出了以下目标：1）利用甲基化谱预测早期结肠癌的复发。2)建立结直肠癌转移过程中的甲基化改变，以鉴定预测复发和转移的新标志物3）开发结直肠癌的分子分期系统。这项研究将建立在令人兴奋的初步结果的基础上，这些结果证明了甲基化谱在预测复发方面的实用性。此外，将对结直肠癌发生的晚期事件进行系统的了解。相关性：结直肠癌是全球和美国癌症死亡的主要原因。这项提案的长期目标是利用新兴领域的知识，称为表观遗传学，建立新的标记物，用于预测结直肠癌复发的高风险患者，并定义新的癌症治疗方法。

DESCRIPTION (provided by applicant): This mentored career award outlines a five-year training program for Dr. Ahuja's transition to scientific independence in the field of cancer biology. Dr. Ahuja proposes to expand her scientific skills and knowledge and it is expected that she would attain independent investigator status at the end of this award period. Dr. Ahuja will continue an established scientific mentorship with Dr. Baylin, an expert in epigenetics. She will also be mentored by Dr. Leach, an expert in pancreatic developmental biology and a fellow surgeon who will provide valuable clinical guidance. She has the full support of her Department to protect at least 75% of her time during the award period. Dr. Ahuja has laboratory and office space within Dr. Baylin's laboratory and is fully immersed in the research environment. The laboratory is located in the Cancer Research Buildings at Johns Hopkins and has access to many established scientists with an environment that favors collaboration and support of clinician scientists. The research plans focuses on understanding the role of DNA methylation in colorectal cancer metastases and recurrence and understand its applicability as translational markers. Epigenetic gene silencing involving aberrant DNA methylation of promoter-associated CpG islands functions as a central mechanism of inactivation of tumor-suppressor genes in colorectal cancer. We hypothesize that methylation profiles hold enormous potential as prognostic markers for recurrence in colorectal cancer and methylation profiles may allow molecular staging of colorectal cancer. In order to test these hypotheses, the following aims are proposed: 1) To utilize methylation profiles to predict recurrence in early-stage colon cancers. 2) To establish the methylation changes that underlie the process of metastasis in colorectal cancers in order to identify novel markers for predicting recurrence and metastases 3) To develop a molecular staging system for colorectal cancer. The research will build on exciting preliminary results demonstrating the utility of methylation profiles to predict recurrence. In addition, a systematic understanding of late events in colorectal carcinogenesis will be performed. Relevance: Colorectal cancer is a leading cause of cancer death worldwide and in the United States. The long-term goal of this proposal is to utilize knowledge of the newly emerging field, termed epigenetics, to establish novel markers for predicting patients at high-risk for colorectal cancer recurrence and to define novel cancer treatments.