Eventos

Speaker: Amita Sehgal, PhD. – John Herr Musser Professor of Neuroscience – Vice Chair, Department of Neuroscience – Director, Chronobiology Program, Perelman School of Medicine, University of Pennsylvania | Philadelphia, United States.

Abstract:

Circadian (~24 hour) rhythms of behavior and physiology are generated by endogenous clocks located within tissues of almost all organisms.  We now have some understanding of how these clocks are generated and how they synchronize to environmental signals. However, mechanisms by which clocks drive rhythms of downstream processes, and how disruption of clocks contributes to pathological conditions are not well understood. We find that the circadian clock drives rhythms in components of the cell cycle, which provides a mechanism for effects of circadian disruption on cancer progression.  A chemotherapeutic drug targeted to such a rhythmic component has time-of-day specific effects in cells and in a mouse tumor model. In fact, we find that, of 126 anti-cancer drugs we screened, ~half work better at a specific time of day. As many of these temporal effects require clocks within tumors, we have also addressed the question of why some tumors have clocks while others don’t.  In other work, to address the relationship between aging and circadian disruption, we have investigated how circadian regulation of downstream genes changes with age.