Non-coding RNAs in head and neck cancer, Proteolytic regulation of synaptic development, Systematic circadian disruption in human cancer

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• Angela Zou & Jarrod Shilts (University of Cambridge)
• Tuesday 20 February 2018, 19:30-20:30
• Club Room, Churchill College.

If you have a question about this talk, please contact Angela Harper.

Non-coding RNAs in head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease marked by frequent recurrence and metastasis and stagnant survival rates. To enhance molecular knowledge of HNSCC , we profiled the transcriptome-wide dysregulation of non-coding RNAs using RNA -sequencing data from HNSCC patients in The Cancer Genome Atlas (TCGA). Our analyses identified a number of differentially expressed non-coding transcripts in HNSCC which are significantly correlated with patient survival, tumor stage, HPV status and other clinical characteristics and/or associated with driver mutations and copy number variations. Modulation of selected non-coding RNAs in vitro reveals differential regulation of genes involved in epithelial-mesenchymal transition and apoptotic response. Our characterization of the HNSCC non-coding transcriptome introduces new layers of understanding for the disease and nominates a novel panel of transcripts with potential utility as prognostic markers or therapeutic targets.

Proteolytic regulation of synaptic development

The developing nervous system must coordinate a complex biological program for neurons to properly establish synaptic connections. Aberrations in this process underlie a spectrum of neurodevelopmental disorders. Experimental models and human clinical trials have suggested that inhibiting the activity of proteases in the extracellular matrix around neurons holds promise in correcting neurodevelopmental defects. Using a range of targeted genetic manipulations in a Drosophila model of synaptic development, we identified a molecular mechanism linking the balance of proteolytic activity to the regulation of developmental signals mediating proper synapse architecture and function. These studies reveal how varying proteolytic dynamics can instruct neural development, and suggest therapeutic targets for treating neurodevelopmental disorders.

Systematic circadian disruption in human cancer

Nearly every cell in the human body possess an internal clock that mediates daily rhythms in growth and metabolism. Multiple lines of evidence implicate disruptions of this circadian clock in cancer. However, it has yet to be determined whether, and if so how, the clock itself is ticking inside human tumors. We developed a simple computational approach to infer the progression of the circadian clock using publicly-available gene expression data. In a survey of 12 cancer types, we find widespread patterns of clock dysregulation that are distinct from those caused by core clock mutations. An analysis of the circadian transcriptome in lung tumors revealed systematic upregulation of genes normally expressed at particular phases of the clock. Our approach opens the way to analyzing the role of the circadian clock in cancer progression and a range of other disease states.

This talk is part of the Churchill Scholars Overly Awesome Research Symposium (ChuSOARS) series.

This talk is included in these lists:

• Churchill Scholars Overly Awesome Research Symposium (ChuSOARS)
• Club Room, Churchill College

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