Circadian Physiology Program

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital
Director: Steven W. Lockley, Ph.D.

Research

The Circadian Physiology Program focuses on basic and applied aspects of human circadian biology. Our translational approach includes use of a range of techniques including epidemiology, field-based physiological studies and inpatient intensive physiological monitoring.

We have a particular interest in human circadian photoreception and the effects of light on the circadian pacemaker and other non-image forming responses. Our studies include investigations of the effects of timing, duration, intensity and wavelength of light exposure on circadian resetting, melatonin suppression and the acute alerting effects of light. We are also conducting a series of applied lighting interventions to improve circadian rhythms, sleep and performance on the International Space Station and other NASA analogs, care homes, hospitals, and offices. This work is also being translated into architectural lighting design approaches and lighting standards.

We have studied visually impaired individuals under field and laboratory conditions to examine the effects of the severity and type of blindness on circadian photoreception, the periodicity of the circadian pacemaker and development of circadian rhythm sleep disorders, which led to the development of novel therapeutic strategies to treat non-24-hour sleep wake disorder in the blind, as well as other health risks such as breast cancer.

We have also conducted field and laboratory studies to assess the wider impact of circadian rhythms on a range of physiological systems including immune response, bone metabolism, reproductive function, liver function and lipid and glucose regulation, and are examining these systems in shiftwork and dementia. We are also identifying and validating a series of biomarkers to measure circadian phase and sleepiness under real-world conditions including lipidomics, metabolomics and urinomics and assessing other real-time circadian assessment technologies.

With the Harvard Work Hours Health and Safety Group, we assess the impact of extended work hours on health and safety of workers and the public. Our studies include the development of interventions that reduce extended duration work hours, fatigue and medical errors in hospital residents, and the implementation of large-scale occupational fatigue management and sleep disorders screening programs in police and firefighters nationwide.

Contact

Circadian Physiology Program
Division of Sleep and Circadian Disorders,
Departments of Medicine and Neurology
Brigham and Women’s Hospital
221 Longwood Avenue, RF-489
Boston, MA 02115
Tel: 617 732 4977
Fax: 617 732 4015
Email: slockley@hms.harvard.edu

Group Members

Circadian Physiology Group
Circadian Physiology Program Group at the 2018 Sleep Health and Benefits Dinner: (L-R) Shadab A. Rahman, Leilah K. Grant, Brianne A. Kent, Melissa A. St. Hilaire, Steven W. Lockley, Ph.D.

 

Faculty

Steven W. Lockley, Ph.D.
Director, Circadian Physiology Program
Neuroscientist, Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital
Associate Professor of Medicine, Harvard Medical School
Professor and VC Fellow, Surrey Sleep Research Centre, University of Surrey, UK

Shadab A. Rahman, Ph.D., M.P.H.
Associate Neuroscientist, Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital
Instructor in Medicine, Harvard Medical School

Melissa A. St. Hilaire, Ph.D.
Associate Biostatistician, Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital
Instructor in Medicine, Harvard Medical School

Research Fellows

Brianne A. Kent, Ph.D.
Research Fellow in Medicine, Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital
Research Fellow in Medicine, Harvard Medical School

Leilah K. Grant, Ph.D.
Research Fellow in Medicine, Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital
Research Fellow in Medicine, Harvard Medical School

Research Assistant

Matthew Mayer, B.A.

Affiliated Faculty

Shantha M. W. Rajaratnam, Ph.D.
Professor, Monash University, Australia
Sleep and Circadian Rhythms Program
School of Psychological Sciences
Deputy Head, School of Psychological Sciences
Deputy Director, Turner Institute for Brain and Mental Health
Lecturer in Medicine (Academic, part-time), Harvard Medical School

Former Faculty and Fellows
  • Adriana Lira-Oliver, D.Des.
  • Joshua J. Gooley, Ph.D.
  • Eliza Van Reen, Ph.D.
  • Kate E. Crowley, Ph.D.
  • Brian K. Abaluck, M.D.
  • Melanie Rüger, Ph.D.
  • Joseph T. Hull, Ph.D.
  • Erin E. Flynn-Evans, Ph.D.
Former and Current (*) PhD students
  • Joseph T. Hull (in collaboration with University of Surrey)
  • Erin E. Flynn-Evans (in collaboration with University of Surrey)
  • Julia Shekleton (in collaboration with Monash University)
  • Suzanne Ftouni (in collaboration with Monash University)
  • María L. Ámundadóttir (in collaboration with EPFL)
  • Simonne Cohen (in collaboration with Monash University)
  • Leilah K. Grant (in collaboration with Monash University)
  • Julia E. Stone (in collaboration with Monash University)
  • *Saranea Ganesan (in collaboration with Monash University)
  • *Laura J. Connolly (in collaboration with Monash University)
  • *Lauren J. Bulfin (in collaboration with Monash University)
  • *Lauren A. Booker (in collaboration with IBAS and Monash University)
Collaborators

Brigham and Women’s Hospital, Boston

  • Laura K. Barger, Ph.D.
  • Charles A. Czeisler, Ph.D., M.D.    
  • Hadine Joffe, M.D.
  • Elizabeth B. Klerman, M.D., Ph.D.    
  • Bruce S. Kristal, Ph.D.
  • Christopher P. Landrigan, M.D., M.P.H.    
  • Julian N. Robinson, M.D.
  • Jason P. Sullivan, B.S.
Current National and International Collaborators
  • George C. Brainard, Ph.D., Thomas Jefferson University, Philadelphia
  • Derk-Jan Dijk, Ph.D., Surrey Sleep Research Centre, University of Surrey, UK
  • Erin E. Flynn-Evans, Ph.D., NASA Ames, Moffett Field
  • Jennie Ponsford, Ph.D., Monash University, Melbourne, Australia
  • Christoph Reinhart, Ph.D., MIT, Cambridge
  • John Spengler, Ph.D., and Jose Guillermo (Memo) Cedeno Laurent, HSPH, Boston
  • Paula A. Witt-Enderby, Ph.D., Duquesne University, Pittsburgh

 

Selected Recent Publications

[Full for list, click on Circadian Physiology Group Members' Papers]

  1. Lockley SW. Guideline for authors: Measuring melatonin in humans. Journal of Pineal Research 2020, in press. PMID: 32344453
  2. Rahman SA, Rood D, Trent N, Solet J, Langer EJ*, Lockley SW*. Manipulating sleep duration perception changes cognitive performance – An exploratory analysis. Journal of Psychosomatic Research 2020; 132. in press.
  3. Klerman EB, Rahman SA, St Hilaire MA. What time is it? A tale of three clocks, with implications for personalized medicine. Journal of Pineal Research 2020; 68(4):e12646.
  4. Grant LK, Gooley JJ, St Hilaire MA, Rajaratnam SMW, Brainard GC, Czeisler CA, Lockley SW, Rahman SA. Menstrual phase-dependent differences in neurobehavioral performance: The role of temperature and the progesterone/estradiol ratio. Sleep 2020; 43(2). pii: zsz227.
  5. Booker LA, Barnes M,  Alvaro P, Collins A, Chai-Coetze CL, McMahon M, Lockley SW, Rajaratnam SMW, Howard ME. Sletten TL. The role of sleep hygiene in the risk of Shift Work Disorder in nurses. Sleep 2020; 43(2). pii: zsz228. PMID: 31637435
  6. Rahman SA, Wright Jr KP, Lockley SW, Czeisler CA, Gronfier C. Characterizing the temporal dynamics of melatonin and cortisol changes in response to nocturnal light exposure. Scientific Reports 2019; 9(1):19720. PMID: 31873098 PMCID: PMC6928018
  7. Peterson SA*, Wolkow AP*, Lockley SW, O’Brien CS, Qadri S, Sullivan JP, Czeisler CA, Rajaratnam SMW, Barger LK. Associations between shift work characteristics, shift work schedules, sleep and burnout in North American police officers: a cross-sectional study. BMJ Open 2019; 9(11):e030302. PMID: 31791964 PMCID: PMC6924705
  8. St. Hilaire MA, Kristal BS, Rahman SA, Sullivan JP, Quackenbush J, Duffy JF, Barger LK, Gooley JJ, Czeisler CA, Lockley SW. Using a single daytime performance test to identify most individuals at high-risk for performance impairment during extended wake. Scientific Reports 2019; 9(1):16681. PMID: 31723161 PMCID: PMC6853981
  9. Kronauer RE*, St Hilaire MA*, Rahman SA, Czeisler CA, Klerman EB. An exploration of the temporal dynamics of circadian resetting responses to short- and long-duration light exposures: cross-species consistencies and differences. Journal of Biological Rhythms 2019; in press. PMID: 31368391
  10. Rahman SA, Grant LK, Gooley JJ, Rajaratnam SMW, Czeisler CA, Lockley SW. Endogenous circadian regulation of female reproductive hormones. Journal of Clinical Endocrinology and Metabolism 2019; 104(12):6049-6059. PMID: 31415086
  11. Rahman SA, Bibbo C, Olcese J, Czeisler CA, Robinson JN, Klerman EB. Relationship between endogenous melatonin concentrations and uterine contractions in late third trimester of human pregnancy. Journal of Pineal Research 2019; 66(4):e12566. PMID: 30739346
  12. Gladanac B, Jonkman J, Shapiro CM, Brown TJ, Ralph MR, Casper RF, Rahman SA. Removing short wavelengths from polychromatic white light attenuates circadian phase resetting in rats. Frontiers in Neuroscience 2019; 13:954. PMID: 31551702
  13. Stone JE, Aubert XL, Maass H, Phillips AJK, Magee M, Howard ME, Lockley SW, Rajaratnam SMW, Sletten TL. Application of a limit-cycle oscillator model for prediction of circadian phase in rotating night shift workers. Scientific Reports 2019; 9(1):11032. PMID: 31363110 PMCID: PMC6667480
  14. Stone JE, Phillips AJK, Ftouni S, Magee M, Howard M, Lockley SW, Sletten TL, Anderson C, Rajaratnam SMW, Postnova S. Generalizability of a neural network model for circadian phase prediction in real-world conditions. Scientific Reports 2019; 9(1):11001. PMID: 31358781 PMCID: PMC6662750
  15. Phillips AJK*, Vidafar P*, Burns AC, McGlashan EM, Anderson C, Rajaratnam SMW, Lockley SW, Cain SW. High sensitivity and interindividual variability in the response of the human circadian system to evening light. Proceedings of the National Academy of Science USA 2019; 116(24):12019-12024. PMID: 31138694 PMCID: PMC6575863
  16. Ganesan S, Magee M, Stone JE, Mulhall MD, Collins A, Howard ME, Lockley SW, Rajaratnam SMW, Sletten TL. The impact of shiftwork on sleep, alertness and performance in healthcare workers. Scientific Reports 2019; 9(1):4635. PMID: 30874565 PMCID:   PMC6420632
  17. Grant LK, Ftouni S, Nijagal B, De Souza DP, Tull D, McConville MJ, Rajaratnam SW, Lockley SW, Anderson C. Circadian and wake-dependent changes in human plasma polar metabolites during prolonged wakefulness: A preliminary analysis. Scientific Reports 2019; 9(1):4428. PMID: 30872634 PMCID: PMC6418225
  18. St. Hilaire MA, Anderson C, Anwar J, Sullivan JP, Cade BE, Flynn-Evans EE, Czeisler CA, Lockley SW; for the Harvard Work Hours Health and Safety Group. Brief (<4 hour) sleep episodes are insufficient for restoring performance in first-year resident physicians working overnight extended-duration work shifts. Sleep 2019; 42(5). PMID: 30794317
  19. Sletten TL, Magee M, Murray JM, Gordon CJ, Lovato N, Kennaway DJ, Gwini SM, Bartlett DJ, Lockley SW, Lack LC, Grunstein RR, Rajaratnam SMW; for the Delayed Sleep on Melatonin (DelSoM) Study Group. Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial. PLoS Medicine 2018; 15(6):e1002587. PMID: 29912983 PMCID: PMC6005466
  20. Vidafar P, Gooley JJ, Burns AC, Rajaratnam SMW, Rueger M, Van Reen E, Czeisler CA, Lockley SW, Cain SW. Increased vulnerability to attentional failure during acute sleep deprivation in women depends on menstrual phase. Sleep 2018; 41(8). PMID: 29790961
  21. Rahman SA, St. Hilaire MA, Gronfier C, Chang AM, Santhi N, Czeisler CA, Klerman EB, Lockley SW. Functional decoupling of melatonin suppression and circadian phase resetting in humans. Journal of Physiology 2018; 596(11):2147-2157. PMID: 29707782
  22. Hull JT, Czeisler CA, Lockley SW. Suppression of melatonin secretion in totally visually blind people by ocular exposure to white light: Clinical characteristics. Ophthalmology 2018; 125(8):1160-1171. PMID: 29625838
  23. Watson LA, Phillips AJK, Hosken IT,  McGlashan EM, Anderson C, Lack LC, Lockley SW, Rajaratnam SMW, Cain SW. Increased sensitivity of the circadian system to light in Delayed Sleep-Wake Phase Disorder. Journal of Physiology 2018; 596(24):6249-6261. PMID: 30281150
  24. Abeysuriya RG, Lockley SW, Robinson PA, Postnova S. A unified model of melatonin, 6-sulfatoxymelatonin, and sleep dynamics. Journal of Pineal Research 2018; 64(4):e12474. PMID: 29437238
  25. St. Hilaire MA, Rahman SA, Gooley JJ, Witt-Enderby PA, Lockley SW. Relationship between melatonin and bone resorption rhythms in premenopausal women. Journal of Bone and Mineral Metabolism 2019; 37(1):60-71. PMID: 29318392
  26. Anderson C, Ftouni S, Ronda JM, Rajaratnam SMW, Czeisler CA, Lockley SW. Self-reported drowsiness and safety outcomes while driving after an extended duration work shift in trainee physicians. Sleep 2018; 41(2) zsx195. PMID: 29281091
  27. Cohen S*, Fulcher BD*, Rajaratnam SMW, Conduit R, Sullivan JP, St Hilaire MA, Philips AJK, Loddenkemper T, Kothare SV, McConnell K, Braga-Kenyon P, Ahearn W, Schlesinger A, Potter J, Bird F, Cornish KM, Lockley SW. Sleep patterns predictive of daytime challenging behavior in individuals with low-functioning autism. Autism Research 2018; 11(2):391-403. PMID: 29197172
  28. Kelley P, Lockley SW, Kelley J, Evans MDR. Is 8:30 a.m. still too early to start school? A 10:00 a.m. school start time improves health and performance of students aged 13-16. Frontiers in Human Neuroscience 2017; 11:588. PMID: 29276481 PMCID: PMC5727052
  29. Cohen S, Fulcher BD, Rajaratnam SMW, Conduit R, Sullivan JP, St Hilaire MA, Phillips AJ, Loddenkemper T, Kothare SV, McConnell K, Ahearn W, Braga-Kenyon P, Schlesinger A, Potter J, Bird F, Cornish KM, Lockley SW. Behaviorally-determined sleep phenotypes are robustly associated with adaptive functioning in individuals with low-functioning autism. Scientific Reports 2017; 7(1):142287. PMID: 29079761 PMCID: PMC5660229
  30. Flynn-Evans EE, Shekleton JA, Miller B, Epstein LJ, Kirsch D, Brogna LA, Burke LM, Bremer E, Murray JM, Gehrman P, Rajaratnam SMW, Lockley SW. Circadian phase and phase angle disorders in primary insomnia. Sleep 2017; 40(12). PMID: 29029340
  31. Phillips AJK*, Clerx WM*, O’Brien CS, Sano A, Barger LK, Picard RW, Lockley SW, Klerman EB, Czeisler CA. Irregular sleep/wake patterns are associated with poorer academic performance and delayed circadian and sleep/wake timing. Scientific Reports 2017; 7(1):3216. PMID: 28607474 PMCID: PMC5468315
  32. Rahman SA, St. Hilaire MA, Lockley SW. The effects of spectral tuning of evening ambient light on melatonin suppression, alertness and sleep. Physiology and Behavior 2017; 177: 221-229. PMID: 28472667
  33. Rahman SA, St. Hilaire MA, Chang AM, Santhi N, Duffy JF, Kronaeur RE, Czeisler CA, Lockley SW, Klerman EB. Circadian phase resetting by a single short-duration light exposure. JCI Insight 2017; 2(7):e89494. PMID: 28405608 PMCID: PMC5374060
  34. St. Hilaire MA*, Rüger M*, Fratelli F, Hull JT, Phillips AJK, Lockley SW. Modeling neurocognitive decline and recovery during repeated cycles of extended sleep and chronic sleep deficiency. Sleep 2017; 40(1). doi: 10.1093/sleep/zsw009. PMID: 28364449
  35. Murray JM, Sletten TL, Magee M, Gordon C, Lovato N, Bartlett DJ, Kennaway DJ, Lack LC, Grunstein RR, Lockley SW, Rajaratnam SMW. Delayed Sleep on Melatonin (DelSoM) Study Group. Prevalence of circadian misalignment and its association with depressive symptoms in delayed sleep phase disorder. Sleep 2017; 40(1). doi: 10.1093/sleep/zsw002. PMID: 28364473
  36. Sullivan JP, O’Brien CS, Barger LK, Rajaratnam SMW, Czeisler CA, Lockley SW; The Harvard Work Hours, Health and Safety Group. Randomized, prospective study of the impact of a workplace-based sleep health program on firefighter injury and disability. Sleep 2017; 40(1). doi: 10.1093/sleep/zsw001. PMID: 28364446
  37. Grima NA, Ponsford JL, St Hilaire MA, Mansfield D, Rajaratnam SM. Circadian melatonin rhythm following traumatic brain injury. Neurorehabilitation and Neural Repair 2016; 30(10):972-977. PMID: 27221043
  38. Rahman SA, Castanon-Cervantes O, Scheer FAJL, Shea SA, Czeisler CA, Davidson AJ, Lockley SW. Endogenous circadian regulation of pro-inflammatory cytokines and chemokines in the presence of bacterial lipopolysaccharide in humans. Brain, Behavior, and Immunity 2015; 47:4-13. PMID: 25452149.
  39. Barger LK, Rajaratnam SM, Wang W, O'Brien CS, Sullivan JP, Qadri S, Lockley SW, Czeisler CA; The Harvard Work Hours Health and Safety Group. Common sleep disorders increase risk of motor vehicle crashes and adverse health outcomes in firefighters. Journal of Clinical Sleep Medicine 2015; 11(3):233-240. PMID: 25580602. PMCID: PMC4346644.
  40. St. Hilaire MA, Lockley SW. Caffeine does not entrain the circadian clock but improves daytime alertness in blind patients with non-24-hour rhythms [Brief Communication]. Sleep Medicine 2015; 16(6):800-4. PMID: 25891543 PMCID: PMC4465963
  41. Lockley SW, Dressman MA, Licamele L, Xiao C, Fisher DM, Flynn-Evans EE, Hull JT, Torres R, Lavedan C, Polymeropoulos MH. Two multicentre randomised trials of tasimelteon for treatment of Non-24-Hour Sleep-Wake Disorder in the blind. The Lancet 2015; 386(10005): 1754-1764. PMID: 26466871
 
Selected Recent Research Support

Seoul Semiconductor (PI: Rahman)        01/11/19-01/10/24 
Investigator-initiated study “Effects of daytime lighting conditions on students' cognitive performance”
The goal is to assess the role light spectrum and intensity on the alerting effects of daytime light exposure. 

FAA    (Co-PIs: Klerman, Czeisler)        09/18/19-09/17/21
FAA “Comparison across multiple types of sleep deprivation”.
This contracted work will collect data for the FAA for discovery of biomarkers associated with neurobehavioral or cognitive impairment during sleep loss and mistimed sleep. Role: Co-Investigator

PNNL    (PI: Rahman)                09/10/19-08/31/21
Investigator-initiated study “analyzing de-identified patient data for an inpatient behavioral health unit research”
The goals are to assess the role of light on health outcomes in an inpatient facility. Role: Co-Investigator

1R21NR018974 (PI: St Hilaire)         09/25/19-07/31/21
NINR ‘Urine metabolomics to estimate internal clock time’
The goals are to develop a feasible method to measure circadian phase accurately and reliably using non-invasive urinomics. Role: Co-Investigator

F.lux Software, LLC    (PI: Lockley)        08/28/15-08/27/20        
Investigator-initiated study “Measuring the effects of light from electronic devices on sleep”
We propose to conduct a randomized clinical trial on the effects of reducing blue content of light emitted from electronic devices on sleep using the F.Lux software.

NNX15AC14G (Co-PIs: Brainard, Lockley)    12/01/14-09/30/20
NASA “Testing solid state lighting countermeasures to improve circadian adaptation, sleep, and performance during high fidelity analog and flight studies for the International Space Station”. 

NNX15AM28G    (PI: Lockley)        08/13/15-06/30/20 
NASA “Lighting Protocols for Exploration – HERA Campaign” 
The study will examine the feasibility and efficacy of a Dynamic Lighting System to improve alertness, sleep and circadian rhythms in the Human Exploration Research Analog.

Recently completed

NNX14AK53G (PI: Lockley)            08/01/14-01/31/20 (NCE)    
NSBRI “Development and testing of biomarkers to determine individual astronauts’ vulnerabilities to behavioral health disruptions”
This study will evaluate biomarkers that will test the sensitivity of various sleep and circadian challenges to differentiate individuals.

Midwest Lighting Institute (PI: Rahman)    01/01/18-12/31/19
“Senior care facility lighting to improve health, safety and energy efficiency”.
The goal of this project is to examine the impact of a dynamic lighting intervention on the health and safety of seniors living in care homes. Role: Co-Investigator.

1R01HL132556 (PI: Kristal)            04/18/16-03/31/20        
NHLBI “Circadian Lipidomics in Constant Routine, Forced Desynchrony, and Non-lab Setting”
The goals of this project are to identify, optimize, validate, and to cross-validate a set of nested plasma lipidomics-based biomarker profiles that report circadian phase. 

 

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