题目: Splicing dysregulation in cancer and neurodegenerative disease

时间:2018年11月28日13:30

地点：理科楼430室

报告人: James Manley教授

报告人介绍:

    James Manley博士现为美国哥伦比亚大学冠名终身教授,美国科学院院士、生物化学部主任；美国科学和艺术学院院士；美国科学促进会会士；担任Molecular Cell, Genes & Development, eLife, Nucleic Acids Research, Molecular and Cellular Biology, Journal of Virology 等多种学术刊物的编委;在包括Cell, Nature, Science等学术刊物发表论文300多篇，是mRNA剪接和多聚腺苷化加尾过程研究领域的国际权威。

报告摘要:

    It has been known for decades that defects in mRNA processing can cause, or contribute to, numerous human diseases. The earliest examples of this involved simply mutations in cis-acting signal sequences (e.g., for splicing and polyadenylation) of target genes, for example the human β-globin gene in β-thalassemia. But the numbers of diseases linked to defects in mRNA processing have increased dramatically in the last five-ten years, reflecting in large part insights from deep-sequencing efforts. Indeed, other more interesting mechanisms beyond cis-mutations have emerged, including changes in the concentrations of RNA binding regulatory proteins (RBPs) and other processing factors, and also mutations that affect the function of not only regulatory proteins but also components of the core splicing machinery, have been observed in a number of human diseases, including various cancers as well as several neurodegenerative diseases. My lab is currently studying how mutations in genes encoding splicing factors contribute to Myelodysplastic Syndromes and other cancers, and how dysregulation of splicing regulatory RBPs can contribute to cancer, using Glioblastoma as a model. We also study how sequestration/aggregation of RBPs in the brain contributes to neurodegenerative disease such as Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.