CLOCKS & CANCER
Circadian rhythms organize the temporal basis for many events in cellular physiology, including the timing of cell division. While we know that circadian disruption (by jet lag and late night shift work) can increase cancer risk, it's not well understood how disease states can perturb clock function.
Based on its evolutionary relationship to the core circadian protein CLOCK, we identified a tissue-specific repressor of circadian rhythms, the PAS domain-containing protein 1 (PASD1).
PASD1 is a cancer/testis antigen, meaning that it is only expressed in germline tissues in healthy individuals, but can be upregulated in a wide array of human cancers.
We showed that PASD1 interacts with the primary circadian transcription factor, CLOCK:BMAL1, to inhibit its activity and suppress circadian cycling. Working with Alison Banham's group at the University of Oxford, we showed that reducing PASD1 expression in human cancer cells significantly improves clock function.
We are currently working on identifying the molecular basis of PASD1 function and discovering new, cancer-induced proteins that interfere with normal clock function.