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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24HL076446-02
Application #
6909786
Study Section
Special Emphasis Panel (ZHL1-CSR-J (F1))
Program Officer
Rothgeb, Ann E
Project Start
2004-06-20
Project End
2009-05-31
Budget Start
2005-06-01
Budget End
2006-05-31
Support Year
2
Fiscal Year
2005
Total Cost
$122,888
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Chang, Anne-Marie; Bjonnes, Andrew C; Aeschbach, Daniel et al. (2016) Circadian gene variants influence sleep and the sleep electroencephalogram in humans. Chronobiol Int 33:561-73
Hu, Kun; Riemersma-van der Lek, Rixt F; Patxot, Melissa et al. (2016) Progression of Dementia Assessed by Temporal Correlations of Physical Activity: Results From a 3.5-Year, Longitudinal Randomized Controlled Trial. Sci Rep 6:27742
Butler, Matthew P; Smales, Carolina; Wu, Huijuan et al. (2015) The Circadian System Contributes to Apnea Lengthening across the Night in Obstructive Sleep Apnea. Sleep 38:1793-801
Thosar, Saurabh S; Wiggins, Chad C; Shea, Steven A et al. (2015) Brachial artery endothelial function is stable across the morning in young men. Cardiovasc Ultrasound 13:42
Swanson, Christine M; Shea, Steven A; Stone, Katie L et al. (2015) Obstructive sleep apnea and metabolic bone disease: insights into the relationship between bone and sleep. J Bone Miner Res 30:199-211
Morris, Christopher J; Yang, Jessica N; Garcia, Joanna I et al. (2015) Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans. Proc Natl Acad Sci U S A 112:E2225-34
Rahman, Shadab A; Castanon-Cervantes, Oscar; Scheer, Frank A J L et al. (2015) Endogenous circadian regulation of pro-inflammatory cytokines and chemokines in the presence of bacterial lipopolysaccharide in humans. Brain Behav Immun 47:4-13
Hsieh, Wan-Hsin; Escobar, Carolina; Yugay, Tatiana et al. (2014) Simulated shift work in rats perturbs multiscale regulation of locomotor activity. J R Soc Interface 11:
Scheer, Frank A J L; Shea, Steven A (2014) Human circadian system causes a morning peak in prothrombotic plasminogen activator inhibitor-1 (PAI-1) independent of the sleep/wake cycle. Blood 123:590-3
Scheer, Frank A J L; Morris, Christopher J; Shea, Steven A (2013) The internal circadian clock increases hunger and appetite in the evening independent of food intake and other behaviors. Obesity (Silver Spring) 21:421-3

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