My laboratory research is focused on understanding the neurobiology of the human circadian pacemaker, located in the suprachiasmatic nucleus (SCN) of the hypothalamus, and its interaction with the sleep homeostat, and on applying that knowledge to clinical medicine and occupational health. We are examining the role of the pineal hormone melatonin in the organization of sleep and circadian rhythms. We are investigating the physiological mechanism underlying photic resetting of the human circadian pacemaker, having shown that some blind people without sight can retain normal circadian responsiveness to light. We are now investigating how the timing, duration, intensity and wavelength of light affects its circadian resetting capacity, which is mediated through intrinsically photosensitive retinal ganglion cells containing the novel photopigment melanopsin. Current research is aimed at functional determination of the photoreceptor(s) responsible for circadian vision in humans, on adaptation of circadian photoreceptors and on the after-effects of entrainment on circadian period in humans. We are investigating how circadian and homeostatic processes interact to regulate sleep and neurobiological function during wakefulness. Other ongoing research in the lab includes examining novel wakefulness- and sleep-promoting countermeasures, the effect of exercise on the circadian pacemaker, fMRI of the sleep deprived brain, the influence of aging on sleep and circadian rhythms, the influence of chronic sleep restriction on human performance, the influence of space flight on sleep and circadian rhythms and the application of our research to night workers-including medical residents and police-through the work of the Harvard Work Hours, Health and Safety Group.