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2015年12月23日周三读书报告会
出处: 发布时间:2015-12-30 浏览次数:27

标题:Low Protein Intake Is Associated with a MajorReduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population

摘要:Mice and humans with growth hormone receptor/IGF-1 deficiencies display major reductions in agerelated diseases. Because protein restriction reduces GHR-IGF-1 activity, we examined links between protein intake and mortality. Respondents aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years.These associations were either abolished or attenuated if the proteins were plant derived. Conversely, high protein intake was associated with reduced cancer and overall mortality in respondents over 65,but a 5-fold increase in diabetes mortality across all

ages. Mouse studies confirmed the effect of high protein intake and GHR-IGF-1 signaling on the incidence and progression of breast and melanoma tumors, but also the detrimental effects of a low protein diet in the very old. These results suggest that low protein intake during middle age followed by moderate to high protein consumption in old adults may optimize healthspan and longevity.

报告人:马腾(林圣彩老师实验室)

课程指导老师:俞春东教授

时间:2015年12月23日 周三下午 4:30

地点:生命科学学院五楼学术报告厅

 

标题:Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

摘要:Tumour oncogenes include transcription factors that co-opt the general transcriptional machinery to sustain the oncogenic state, but direct pharmacological inhibition of transcription factors has so far proven difficult. However, the transcriptional machinery contains various enzymatic cofactors that can be targeted for the development of new therapeutic candidates, including cyclin-dependent kinases (CDKs).Here we present the discovery and characterization of a covalent CDK7 inhibitor, THZ1, which has the unprecedented ability to target a remote cysteine residue located outside ofthe canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7.Cancer cell-line profiling indicates that a subset of cancer cell lines,including human T-cell acute lymphoblastic leukaemia (T-ALL), have exceptional sensitivity to THZ1. Genome-wide analysis in Jurkat T-ALL cells shows that THZ1 disproportionally affects transcription ofRUNX1 and suggests that sensitivity to THZ1 may be due to vulnerability conferred by theRUNX1super-enhancer and the key role ofRUNX1in the core transcriptional regulatory circuitry of these tumour cells. Pharmacological modulation of CDK7 kinase activity may thus provide an approach to identify and treat tumour types that are dependent on transcription for maintenance of the oncogenic state.

报告人:孙细欢(邓贤明老师实验室)

课程指导老师:王洪睿教授

时间:2015年12月23日 周三下午 4:30

地点:生命科学学院五楼学术报告厅