CARCINOGENESIS AND DRUG DEVELOPMENT

描述（申请人描述）：该培训计划的目标是培养能够在与癌症预防和治疗相关的化学科学领域做出原创性研究贡献的科学家。化学系的11名教师组成了核心研究团队，围绕该团队建立了该计划的教育产品。进入该项目的博士预科学生首先要完成严格的课程选择和考试，之后他们将专注于几个可用的研究领域之一，这些研究领域也可供博士后学员使用，以完成他们的博士论文。该项目包括致癌的分子基础、抗癌药物的机制研究、新型抗肿瘤药物的合成以及生物膜功能的化学方法。具体项目包括DNA损伤的细胞反应研究，铂抗癌药物的机制，DNA损伤和致癌过程中的遗传变化，癌症病因学和外源代谢，抗肿瘤抗生素采用的自由基介导的DNA降解机制，分子识别原理设计新的抗肿瘤药物，利用烯丙基作为信号转导的调节剂，阻断导致肿瘤状态的细胞事件，开发新的分析方法来测量环境致癌物，并阐明跨膜蛋白介导的信号转导。一些合成项目包括抗肿瘤和促进肿瘤的天然产物和类似物的合成，具有抗肿瘤活性的复杂碳原子和杂芳香化合物的制备，催化抗体在抗肿瘤靶分子合成中的应用，以及基于机制的核糖核苷酸还原酶二铁中心抑制剂的开发。除了他们的研究，该项目的研究生和博士后学生还需要通过参加定期安排的研讨会项目和参加重要的科学会议来扩展他们的知识。在麻省理工学院，受训者展示他们的研究成果，听取同事的报告，并听取麻省理工学院和大波士顿社区癌症研究人员的各种讲座。后者包括流行病学家和临床肿瘤学家以及基础科学家。这些研讨会使受训者全面了解环境因素在癌症病因学中的作用以及化疗在该疾病的临床管理中的作用。小组会议讨论研究和建议学生也定期举行。在国内和国际会议上，训练奖助金的成员发表论文，并出席与他们自己的计划有关的会议，以及与训练奖助金有关的其他人的计划。然后，他们回到麻省理工学院后，将自己的经历与项目中的其他学员分享。通过指定的阅读和参与与教师定期安排的课程，对学生进行适当的科学行为和科学伦理的教育，在这些课程中，教授们展示和讨论案例研究。除了在定期安排的培训资助研讨会上的互动外，该项目的学生和教师还有许多正式的研究合作。此外，受训者与麻省理工学院其他癌症研究实验室之间也有正式和非正式的合作，包括癌症研究中心、毒理学部门和怀特黑德研究所的实验室。

DESCRIPTION (Applicant's Description): The objective of this Training Program is to produce scientists qualified to make original research contributions in the chemical sciences related to the prevention and treatment of cancer. Eleven faculty members of the Chemistry Department constitute the core research team around which the educational offerings of the program are built. Predoctoral candidates admitted to the program first complete a rigorous selection of courses and examinations after which they concentrate in one of several available research areas, also available to postdoctoral trainees, for their Ph.D. dissertation. Included in this offering are projects in the molecular basis of carcinogenesis, mechanistic studies of anticancer drugs, the synthesis of new antitumor agents, and chemical approaches to the function of biological membranes. Specific projects include studies of cellular responses of DNA damage, the mechanism of platinum anticancer drugs, DNA damage and genetic changes in carcinogenesis, cancer etiology and xenobiotic metabolism, mechanisms of radical-mediated DNA degradation employed by antitumor antibiotics, the principles of molecular recognition to design new antitumor drugs, use of prenyl groups as modulators of signal transduction, interception of cellular events leading to the tumor state, development of new analytical methods to measure environmental carcinogens, and elucidation of signal transduction as mediated by transmembrane proteins. Several synthetic projects include the synthesis of antitumor and tumor-promoting natural products and analogs, the preparation of complex carboaromatic and heteroaromatic compounds exhibiting antitumor activity, the use of catalytic antibodies in synthesis of antitumor target molecules, and the development of mechanism based inhibitors of the diiron center in ribonucleotide reductase. In addition to their research, graduate and postdoctoral students in the program are required to expand their knowledge through participation in a regularly scheduled seminar program and by travel to key scientific meetings. At MIT, trainees present their research results, listen to presentations by their colleagues, and hear a variety of lectures by cancer researchers in the MIT and greater Boston communities. Included in the latter group are epidemiologists and clinical oncologists as well as basic scientists. These seminars give the trainees a comprehensive picture of the roles of environmental factors in the etiology of cancer and of chemotherapy in the clinical management of the disease. Subgroup meetings to discuss research and advise students are also held regularly. At national and international meetings, members of the training grant give papers and attend sessions on work related to their own project as well as the projects of others on the training grant. They then relate their experiences to other trainees in the program upon returning to MIT. Education in the proper conduct of science and in scientific ethics is required through assigned readings and participation in regularly scheduled sessions with the faculty in which case studies are presented and discussed. Apart from their interactions at the regularly scheduled training grant seminars, students and faculty in the program have many formal research collaborations. In addition, there is both formal and informal cooperation among trainees and other MIT cancer research laborato- ries, including those in the Center of Cancer Research, the Toxicology Division, and the Whitehead Institute.