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SUMMARY:Non-coding RNAs in head and neck cancer\, Proteolytic regulation o
 f synaptic development\,  Systematic circadian disruption in human cancer 
 - Angela Zou &amp\; Jarrod Shilts (University of Cambridge)
DTSTART:20180220T193000Z
DTEND:20180220T203000Z
UID:TALK94639@talks.cam.ac.uk
CONTACT:Angela Harper
DESCRIPTION:Non-coding RNAs in head and neck cancer \n\nHead and neck squa
 mous cell carcinoma (HNSCC) is an aggressive disease marked by frequent re
 currence and metastasis and stagnant survival rates. To enhance molecular 
 knowledge of HNSCC\, we profiled the transcriptome-wide dysregulation of n
 on-coding RNAs using RNA-sequencing data from HNSCC patients in The Cancer
  Genome Atlas (TCGA). Our analyses identified a number of differentially e
 xpressed non-coding transcripts in HNSCC which are significantly correlate
 d with patient survival\, tumor stage\, HPV status and other clinical char
 acteristics and/or associated with driver mutations and copy number variat
 ions. Modulation of selected non-coding RNAs in vitro reveals differential
  regulation of genes involved in epithelial-mesenchymal transition and apo
 ptotic response. Our characterization of the HNSCC non-coding transcriptom
 e introduces new layers of understanding for the disease and nominates a n
 ovel panel of transcripts with potential utility as prognostic markers or 
 therapeutic targets.\n\nProteolytic regulation of synaptic development\n\n
 The developing nervous system must coordinate a complex biological program
  for neurons to properly establish synaptic connections. Aberrations in th
 is process underlie a spectrum of neurodevelopmental disorders. Experiment
 al models and human clinical trials have suggested that inhibiting the act
 ivity of proteases in the extracellular matrix around neurons holds promis
 e in correcting neurodevelopmental defects. Using a range of targeted gene
 tic manipulations in a Drosophila model of synaptic development\, we ident
 ified a molecular mechanism linking the balance of proteolytic activity to
  the regulation of developmental signals mediating proper synapse architec
 ture and function. These studies reveal how varying proteolytic dynamics c
 an instruct neural development\, and suggest therapeutic targets for treat
 ing neurodevelopmental disorders.\n\nSystematic circadian disruption in hu
 man cancer\n\nNearly every cell in the human body possess an internal cloc
 k 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 i
 s ticking inside human tumors. We developed a simple computational approac
 h 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 co
 re clock mutations. An analysis of the circadian transcriptome in lung tum
 ors revealed systematic upregulation of genes normally expressed at partic
 ular 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. 
LOCATION:Club Room\, Churchill College
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