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的基因组信息，发现和功能分析了高风险家族和散发性癌症中负责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对它们有反应的基因表达的突变或变异中。基因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”，在这种情况下，细胞在致癌基因和肿瘤抑制基因等关键致癌基因中产生DNA损伤。种系或体细胞突变都会影响信号转导的蛋白质，如生长因子受体途径或转录因子，导致基因表达的变化。同样，表观遗传变化也可以发生在生殖系或体细胞中。对癌症极端风险人群的研究可以应用于癌症风险遗传学更微妙的普通人群。目前，本项目主要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、信号转导的转录调控和翻译后控制机制。我们利用细胞系和整个动物来模拟导致

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.