The applicant has a funded research program in medical chronobiology, and is the Associate Director of an NIH funded Harvard-wide Training Program in Sleep, Circadian & Respiratory Neurobiology. He has a track record and commitment to mentoring clinical researchers. The candidate's immediate goal is to determine the physiological mechanisms underlying the robust day/night pattern in adverse cardiovascular events, and of nocturnal asthma. The long-term goal is to develop a group of outstanding clinical investigators studying complementary aspects of medical chronobiology. A K24 award will enable the applicant to realize these goals by enabling him to relinquish his clinical duties in a sleep disorders program and allowing more protected time for both patient-oriented research and mentoring of clinical research fellows. The environment for this research is outstanding, with over 50 successful research faculty involved with the Harvard-wide Division of Sleep Medicine. There are 'state of the art' research facilities, comprising intensive physiological monitoring suites in a General Clinical Research Center. The candidate has funding to determine the role of the body clock versus sleep in causing nocturnal asthma. The candidate plans to extend these studies in asthma, and to perform parallel studies into the mechanisms underlying the day-night pattern of adverse cardiovascular events, which has a large peak around 9 AM. To this end, a """"""""Forced Desynchrony"""""""" protocol will be used, wherein subjects' behaviors occur at all phases of the circadian cycle.
The aims are to determine the effect upon pulmonary and cardiovascular risk markers of (1) the intrinsic circadian rhythm (independent from behaviors); (2) the pattern in behavior related to the sleep-wake cycle, posture and activity (controlling for circadian phase); (3) any interaction. The biomarkers with potential relevance to cardiovascular vulnerability will include hemodynamic, hemostatic, autonomic and endothelial function measures. The applicant's longer-term goals will be to improve therapy in such disorders via modifications in behavior or chronopharmacology.
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