The purpose of this proposal is two-fold: (1) to provide protected time and support to Dr. Klerman while she mentors graduate students, post-doctoral fellows and junior faculty towards careers in patient-oriented research;and (2) to conduct patient-oriented research related to the effects of light on multiple physiologic functions. Dr. Klerman is actively involved in both patient-oriented experimental work and mathematical analyses and modeling that will enable translation of research results into real-world applications. The mammalian eye serves both visual and non-image-forming functions. Some of the non-visual responses are due to the effect of light on circadian rhythms, the endogenous ~24-hour rhythms generated by a pacemaker in the hypothalamic suprachiasmatic nucleus (SCN). Disruption of the circadian pacemaker or of its normal phase relationship with local time, such as with night or rotating work shifts or jet lag, is associated with illness, errors and accidents. Other non-visual effects of ocular light exposure include melatonin suppression (as a signal for seasonal reproductive changes), pupillary reflexes, and changes in heart rate, performance, and alertness. The SCN receives ocular light stimuli primarily mediated by intrinsically photosensitive retinal ganglion cells, rather than rod and cone photoreceptors. The outputs of the SCN influence almost every physiologic function, including the timing and content of sleep, hormone release, cardiovascular and gastrointestinal function, objective performance, subjective alertness, and mood. We will quantify the effects of light on circadian rhythms and other physiologic functions using experimental, modeling, and database approaches. Experimentally, we will document the effects of short duration light stimuli and the duration of darkness exposure required to reset circadian sensitivity. The data from these experiments will be combined into a database with data from over 2000 subjects already studied in similar protocols. All these data then will be used to refine our validated mathematical model of the effects of light on the human circadian pacemaker. This model and a linked model of circadian and sleep-wake schedule effects on performance and alertness with countermeasure applications will be made available on the internet. The activities outlined in this proposal have implications for science, for public health, and operational (work) situations. The mentoring work will address a critical shortage of researchers in sleep and circadian rhythms, documented in a US Department of Health and Human Services-sponsored National Center on Sleep Disorders Research report. The experimental work is relevant both for understanding the basic physiology of human circadian, hormone, heart rate, performance and alertness functions and for patient-oriented research including retinal/eye care and sleep of older persons. The results can be used to make predictions about the effects of light, to make recommendations involving exposure to or avoidance of light, and to design environmental lighting, resulting in improved health and alertness and decreased errors and accidents.

Public Health Relevance

The purpose of this proposal is two-fold: (1) to provide protected time and support to Dr. Klerman as she continues mentoring graduate students, post-doctoral fellows and junior faculty towards careers in patient- oriented research;and (2) to quantify the effects of short light stimuli on human circadian rhythms, performance, alertness, and other physiologic functions. Narrative The purpose of this proposal is two-fold: (1) to provide protected time and support to Dr. Klerman as she continues mentoring graduate students, post-doctoral fellows and junior faculty towards careers in patient- oriented research;and (2) to quantify the effects of short light stimuli on human circadian rhythms, performance, alertness, and other physiologic functions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24HL105664-05
Application #
8709862
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Twery, Michael
Project Start
2010-09-16
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
Rahman, Shadab A; St Hilaire, Melissa A; Chang, Anne-Marie et al. (2017) Circadian phase resetting by a single short-duration light exposure. JCI Insight 2:e89494
Gu, Fangyi; Xu, Shangda; Devesa, Susan S et al. (2017) Longitude Position in a Time Zone and Cancer Risk in the United States. Cancer Epidemiol Biomarkers Prev 26:1306-1311
Bianchi, Matt T; Phillips, Andrew J K; Wang, Wei et al. (2017) Statistics for Sleep and Biological Rhythms Research. J Biol Rhythms 32:7-17
Klerman, Elizabeth B; Wang, Wei; Phillips, Andrew J K et al. (2017) Statistics for Sleep and Biological Rhythms Research. J Biol Rhythms 32:18-25
McHill, Andrew W; Klerman, Elizabeth B; Slater, Bridgette et al. (2017) The Relationship Between Estrogen and the Decline in Delta Power During Adolescence. Sleep 40:
Swaminathan, Krithika; Klerman, Elizabeth B; Phillips, Andrew J K (2017) Are Individual Differences in Sleep and Circadian Timing Amplified by Use of Artificial Light Sources? J Biol Rhythms 32:165-176
Videnovic, Aleksandar; Klerman, Elizabeth B; Wang, Wei et al. (2017) Timed Light Therapy for Sleep and Daytime Sleepiness Associated With Parkinson Disease: A Randomized Clinical Trial. JAMA Neurol 74:411-418
Shaw, Natalie D; McHill, Andrew W; Schiavon, Michele et al. (2016) Effect of Slow Wave Sleep Disruption on Metabolic Parameters in Adolescents. Sleep 39:1591-9
Bermudez, Eduardo B; Klerman, Elizabeth B; Czeisler, Charles A et al. (2016) Prediction of Vigilant Attention and Cognitive Performance Using Self-Reported Alertness, Circadian Phase, Hours since Awakening, and Accumulated Sleep Loss. PLoS One 11:e0151770
Bendrick, Gregg A; Beckett, Scott A; Klerman, Elizabeth B (2016) Human fatigue and the crash of the airship Italia. Polar Res 35:

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