Molecular Biology and Human Genetics Program

分子生物学和人类遗传学项目分析了从酵母到人类的生物体研究中的基因组信息，发现和功能分析了负责高风险家庭和散发性癌症中癌症易感性的新基因。癌症的发展与细胞基因的一系列变化有关。这些变化发生在致癌基因和其他基因的基因表达突变或变异中，这些基因对它们有反应。遗传改变提供了每种肿瘤类型特有的分子特征。癌症易感基因经常导致所谓的“基因组不稳定性”，其中细胞在关键的致癌基因如癌基因和肿瘤抑制基因中发生DNA损伤。无论是生殖系或体细胞突变影响蛋白质参与信号转导，如生长因子受体途径或转录因子，导致基因表达的变化。类似地，表观遗传变化可以发生在生殖系或体细胞中。对癌症高危人群的研究可以应用于一般人群，因为癌症风险的遗传学更微妙。该计划目前的工作是研究基因组不稳定性机制、染色质结构、细胞周期检查点控制、信号转导的转录调节和翻译后控制机制。我们利用细胞系和整个动物来模拟导致 癌前细胞，癌前病变的分子特征，以及这些细胞发展为瘤形成的关键遗传事件。由于模型生物中DNA修复基因和生长控制机制的遗传信息广泛存在，我们正在应用酵母和小鼠模型系统的遗传学来了解人类基因的结构和功能。我们正在分析具有良好特征的DNA修复和检查点基因的人类同源物在遗传和散发性人类癌症中的作用。这些遗传机制将为早期检测、化学预防和化疗提供有用的分子靶点。这一知识体系也为癌症风险提供了一种新的方法 在特殊人群中。

The Molecular Biology and Human Genetics Program analyzes the genomic information from studies of organisrns from yeast to humans in, the discovery and functional analysis of novel genes responsible for cancer predisposition in high risk families as well as in sporadic cancers. Cancer development is associated with a series of changes in cellular genes. These changes occur as mutations or variations in gene expression in cancer causing genes and in other genes, which respond to them. Genetic alterations provide molecular signatures specific to each tumor type. Cancer susceptibility genes frequently cause so-called "genomic instability" in which cells develop DNA damage in critical cancer-causing genes such as oncogenes and tumor suppressor genes. Either germline or somatic mutations affect proteins involved in signal transduction such as growth factor receptor pathways or transcription factors leading to changes in gene expression. Similarly, epigenetic changes can occur in the germ line or in somatic cells. Studies in human populations at extreme risk to cancer can be applied to the general population in which the genetics of cancer risk is subtler. The current efforts of this Program are on mechanisms of genomic instability, chromatin structure, cell cycle checkpoint control, transcriptional regulation of signal transduction, and post-translational control mechanisms. We utilize cell lines and whole animals to model the genetic mechanisms leading to precancerous cells, the molecular signatures of precancerous lesions, and the critical genetic events in the progression of these cells to neoplasia. Because of the extensive body of genetic information on DNA repair genes and growth control mechanisms in model organisms, we are applying the genetics of yeast and mouse model systems to understand human gone structure and function. We are analyzing the human homologues of well-characterized DNA repair and checkpoint genes for their role in genetic and sporadic human cancers. These genetic mechanisms will provide useful molecular targets for early detection, chemoprevention and chemotherapy. This body of knowledge also provides a novel approach to cancer risk determination in special populations.