Telomere Dysfunction and Cell Death

Gliomas resolve the issue of telomere shortening either by reactivating TERT in connection with TERT promoter mutation, or by using the ALT mechanism.  Inhibition of either of these processes appears to lead to cell death although the mechanisms controlling the processes are undefined.  We have recently become interested in determining how telomeric processing links to cell death pathways. 

Critically short telomeres lead to cell cycle arrest and autophagic elimination in normal cells.  These processes, however, may be disabled in glioma.  Using agents that disrupt telomeric function, we are interested in determining how the damaged telomeric signal is recognized and in identifying pathways that glioma may suppress to survive telomeric dysfunction.