Faculty Profile

Elizabeth B. Klerman, MD, PhD

Dr. Elizabeth Klerman
Associate Professor of Medicine, Harvard Medical School
Physician, Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital

Other Affiliation(s)

MIT  (HST) Training Program in Bioastronautics, Faculty member

See publications


Address

221 Longwood Avenue, Suite 438
Boston, MA 02115
USA

Inter-office Mail Address

Division of Sleep and Circadian Disorders

Phone 617-732-5500 ext.33948
Fax 617-732-4015

Society Memberships

Sleep Research Society
Society for Research in Biological Rhythms
Association for Clinical and Translational Science (ACTS)
International Academy of Astronautics

Research Unit(s)

Analytic and Modeling Unit, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital

Research Interests

Dr. Klerman's current research focuses on the areas of:
(1) the interaction of endocrine, circadian and sleep rhythms in normal and pathological states
(2) mathematical modeling of sleep, circadian system and markers of its function.

Dr. Klerman is Director of the Analytic Modeling Unit within the Division of Sleep Medicine at BWH. She collaborates with investigators from other Divisions to apply the principles of circadian rhythms research to the study of human physiology and pathophysiology. Members of the Analytic and Modeling Unit systematically and mathematically explore many aspects of the sleep and circadian rhythms. The results have implications for the design and analysis of future circadian experiments as well as reinterpretation of earlier studies. This work is part of a cycle of experimental work- mathematical modeling and predictions- experimental work. This Unit's projects have included:
(1) the effects of different patterns of light exposure on observed circadian rhythms,
(2) a reanalysis of data to demonstrate that a method of analysis frequently used in circadian rhythm research yields inaccurate results,
(3) an analysis of three markers of the circadian system for sources of variability, providing quantitative assessment of their relative accuracy as markers of circadian rhythms,
(4) development and application of a physiologically based model of growth hormone secretion with Dr. Emery Brown of MGH and MIT,
(5) development of new techniques for quantifying sleep architecture and its changes with aging and after pharmacological intervention, and
(6) mathematical simulations of models of human circadian rhythms, alertness and performance and optimization of countermeasure design.

Trainees

Undergraduate:
H.B. Gershengorn MD 1997-1998, 2000-2001
J.B. Davis MD 1999-2001
J.C. Kuhn, PhD 2000-2001 (Harvard U. Honors Thesis – magna plus)
P. Greenside 2010-2011 (Harvard U. Honors Thesis – magna)
M. Guha 2007-2008 (Brandeis U. Honors Thesis)
E. Breslow 2012-2013 (Harvard University Honors thesis – (Summa; John E. Dowling Award for Best Thesis in Neurobiology)
J. Zhang 2013-2014 (Harvard University Honors thesis- Magna)
B Slater 2014-present (Harvard University)

Masters, MD and PhD:
Dennis Dean II (U Mass. Lowell) PhD 2004-2011
Melissa St. Hilaire (Boston University PhD ) 2004-2012
R. Torgovitsky (Harvard University)PhD 2007-2008
J. Tarpy Masters 2009-2011
E Bermudez (Morehouse School of Medicine)
M Gupta (Harvard University) PhD candidate 2014-present

Post-doctoral:
P. Indic PhD 2003-2004
C. Diniz-Behn PhD 2006-2007
D. A. Cohen MD MMSc 2006-2008
S. Krishnamanchari PhD 2008-2009
Andrew Phillips PhD 2009- 2013
J. Hull PhD 2012-2013
M. Lee PhD 2012-2014
S. Rahman PhD 2012-present
A McHill PhD 2013-present

Mentor(s)

Charles A. Czeisler, PhD, MD
Gordon H. Williams, MD
Janet E. Hall, MD
Joanne Ingwall, PhD
Ellen Seely, MD

Research Funding

Completed:
NICHD/NIH    Klerman (PI)    2002-2007
"Impact of Sleep Disruption on Menstrual Cycle Dynamics"

NSBRI HPF00405    Klerman (PI)    2004-2008
“Mathematical Models of Circadian/Performance Countermeasures 2004”

AFOSR FA9550-060080    Klerman and Czeisler (Co-PI)    2006-2008
“Interaction of chronic sleep restriction and circadian misalignment on sleep and neuro-cognitive performance: developing a new model of sleep homeostasis”

Takeda Pharmaceuticals (investigator initiated)    Rajaratnam and Klerman (Co-PIs)    2007-2009
“Effects of Ramelteon on Neurobehavioral Performance in a simulated Night Shift Preceded by a Sleep Opportunity”

Respironics (investigator initiated)    Klerman (PI)    2009-2010
”Mathematical modeling of the human circadian pacemaker with applications to actigraphy, alertness, and performance”

NIH R01-HL-114088-02S1 Klerman (PI) 2013-2014
“Sleep duration required to restore performance during chronic sleep restriction” – Administrative supplement to study Sex Differences”

NSBRI HFP01604    Klerman (PI)    2008-2012
"Designing Individual Countermeasures to Reduce Sleep Disruption and Improve Performance and Alertness in Space"

NIH NIA 2P01-AG009975    Czeisler (PI)    2006-2012 
"Sleep, Aging, and Circadian Rhythm Disorders"
Role: PI on Analytic Core within Program Project Grant.

NSBRI HFP01701    Klerman (PI)   2008-2012
Associate Team Leader: "Human Factors and Performance Team"

NIH/NHLBI RC2    Klerman (PI)    2009-2012
“Human circadian sensitivity to very short light pulses”

Current:
NIH K24-HL105664    Klerman (PI)    2010-2015
“Human circadian, sleep, cardiovascular and neurobehavioral responses to light “

NIH R01-HL-114088 Klerman (PI) 2012-2016
"Sleep duration required to restore performance during chronic sleep restriction”

NSBRI HFP02802 Klerman (PI) 2012-2015
" Ultra-short light pulses as an efficient countermeasure for circadian misalignment and objective performance and subjective alertness decrements"

NSBRI HFP02701 Klerman (PI) 2015-2015
Team Leader “Human Factors and Performance Team”

Harvard Milton Fund Klerman (PI) 2013-2015 (NCE)4
“Ocular light exposure as treatment for pre-term labor”

NIH R01-GM-105018 Klerman/Czeisler co-PI 2013-2018
“Multi-scale modeling of sleep behaviors in social networks”

NIH P01-AG009975  (C.A. Czeisler PhD MD, P.I.). 2013-2017. "Sleep, Aging, and Circadian Rhythm Disorders” Core B - Analytic Core (Klerman, PI)

Teaching

Harvard Medical School Holmes Society Research Fellow 2012- present

Awards
Member, International Space Station Flexible Lighting Team that was awarded  NASA Johnson Space Center 2014 Director’s Innovation Award

Recorded Presentations

HMS Talks@Twelve
“Sleep- that thing you don’t get” (March 9, 2011)

Harvard Medical School Podcast
“Are you getting enough sleep?”
(May 23 2011)

Multimedia
Harvard Medicine Magazine
"Space Savers"
(video feature released June 1 2012)

Selected Publications

Original Articles
Dean DA 2nd, Adler GK, Nguyen DP, Klerman EB. Biological time series analysis
using a context free language: applicability to pulsatile hormone data. PLoS One.
2014 Sep 3;9(9):e104087. doi: 10.1371/journal.pone.0104087. eCollection 2014.
PMID: 25184442;  PMCID: PMC4153563.

Faghih RT, Dahleh MA, Adler GK, Klerman EB, Brown AN. Quantifying Pituitary-Adrenal Dynamics and Deconvolution of Concurrent Cortisol and Adrenocorticotropic Hormone Data by Compressed Sensing. IEEE TBME. (in press)

Faghih RT, Dahleh MA, Adler GK, Klerman EB, Brown AN. Deconvolution of Serum Cortisol Levels by Using Compressed Sensing.
PloS One 2014 Jan 28;9(1):e85204. [PMID:24489656; PMC in progress]

Balasubramanian R, Cohen DA, Klerman EB, Pignatelli D, Hall JE, Dwyer AA, Czeisler CA, Pitteloud N, Crowley Jr WF. Absence of central circadian pacemaker abnormalities in humans with loss of function mutation in Prokineticin 2.
J Clin Endoc Metab  2014 Jan 1:jc20132096. . [PMID: 24423319; PMC in progress].

Phillips AJK, Fulcher BD, Robinson PA, Klerman EB. Mammalian Rest/Activity Patterns Explained by Physiologically Based Modeling.
PLoS Computational Biology 2013 ;9(9):e1003213 [PMID: 24039566, PMC in progress].

Phillips AJK, Robinson PA, Klerman EB. Arousal state feedback as a potential physiological generator of the ultradian REM/NREM sleep cycle.
J Theor Biol 2013 Feb 21;319:75-87. PubMed PMID: 23220346].

Breslow ER, Phillips AJK, Huang JM, St. Hilaire MA, Klerman EB. A mathematical model of the circadian phase-shifting effects of exogenous melatonin.
J Biol Rhythms 2013; 28:79-89 [PMID:23382594. PMCID: PMC3733227].

St. Hilaire MA, Sullivan JP, Anderson C, Cohen DA., Barger LK, Lockley SW, Klerman, EB. Classifying performance impairment in response to sleep loss using pattern recognition algorithms on single session testing.
Accident Analysis and Prevention 2013;50:992-1002 [ PMID:22959616. PMCID: PMC3513628.]

Bianchi MT, Wang W, Klerman EB. Sleep misperception  in healthy adults: implications for insomnia diagnosis.
Journal of Clinical Sleep Medicine 2012; 8(5);547-554 [PMID: 23066367, PMCID: PMC3459201]

Klerman EB, Wang W, Duffy JF, Dijk DJ, Czeisler CA, Kronauer RE. Survival analysis indicates that age-related decline in sleep continuity occurs exclusively during NREM sleep.
Neurobiol Aging. 2012 Jun 22. [Epub ahead of print] [PMID: 22727943, PMCID: PMC3469724]

Klerman H, St. Hilaire MA, Kronauer RE, Gooley JJ, Gronfier D, Hull JT, Lockley SW, Santhi N, Wang W, Klerman EB. Analysis Method and Experimental Conditions Affect Computed Circadian Phase from Melatonin Data.
PLoS One 2012 7(4): e33836. [PMID: 22511928, PMCID: PMC3325223]

Phillips AJ, Czeisler CA, Klerman EB. Revisiting spontaneous internal
desynchrony using a quantitative model of sleep physiology.
J Biol Rhythms. 2011  Oct;26(5):441-53. [PMID: 21921298]

Klingman KM, March EE, Klerman EB, Anderson EJ, Hall JE. Absence of circadian rhythms of gonadotropin secretion in women.
J Clin Endoc Metab, 2011: Feb 23 [Epub ahead of print]. [PMID: 21346063].

Cohen DA, Wang W, Klerman EB, Rajaratnam SWMR. Ramelteon prior to a short evening nap impairs neurobehavioral performance for up to 12-hours after awakening.
J Clinical Sleep Medicine, 2010;6:565-571 [PMID: 21206545].

Diniz Behn CGD, Klerman EB, Mochizuki T, Lin S-C, Scammell TE. Abnormal sleep/wake dynamics in orexin knockout mice.
Sleep, 2010, 33:297-306 [PMID 20337187].

Cohen DA, Wang W, Wyatt JK, Kronauer RE, Dijk D-J, Czeisler  CA, Klerman EB. Uncovering residual effects of chronic sleep loss on human performance.
Science Translational Medicine. 2010, 2:14ra3; 1-8 [PMID 20371466].
Note: Featured on cover of online journal. Selected by NASA to include in “Research Progress Reports from the NASA Human Research Program”.

Dean DA 2nd, Forger DB, Klerman EB. Taking the lag out of jet lag through model-based schedule design.
PLoS Comput Biol. 2009 Jun;5(6):e1000418. Epub 2009 Jun 19. [PMID: 19543382]

Rajaratnam SM, Polymeropoulos MH, Fisher DM, Roth T, Scott C, Birznieks G, Klerman EB. Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials.
Lancet. 2009 Feb 7;373(9662):482-91. Epub 2008 Dec 4. Erratum in: Lancet. 2009 Apr 11;373(9671):1252. [PMID: 19054552]

Benloucif S, Burgess HJ, Klerman EB, Lewy AJ, Middleton B, Murphy PJ, Parry
BL, Revell VL. Measuring melatonin in humans.
J Clin Sleep Med. 2008 Feb 15;4(1):66-9. [PMID: 18350967]

Rajaratnam SMW, Polymeropoulos MH, Fisher DM, Roth T, Scott C, Birznieks G, Klerman EB. Randomised controlled trials of the melatonin agonist tasimelteon (VEC 162) for transient insomnia after sleep time shift.
The Lancet 2008; Dec. 2, 2008 (online publication)

Klerman EB, Dijk D-J. Age-related reduction in the maximal capacity for
sleep -implications for insomnia.
Current Biology 2008; 18:1118-1123. [PMID 18656358]

St. Hilaire MA, Gronfier C, Zeitzer JM, Klerman EB. A physiologically-based mathematical model of melatonin including ocular light suppression and interactions with the circadian pacemaker.
J. Pineal Res. 2007; 43:294-304. [PMID 17803528]

Klerman EB, Hilaire MS. Review on mathematical modeling of circadian rhythms, performance, and alertness.
J Biol Rhythms 2007; 22(2):91-102. [PMID: 17440211]

Dean II DA, Fletcher A, Hursh SR, Klerman EB. Developing Mathematical Models of Neurobehavioral Performance for the "Real World".
J Biol Rhythms 2007; 22:246-258. [PMID: 17517914]

Kronauer RE, Gunzelmann G, Van Dongen HP, Doyle FJ, III, Klerman EB. Uncovering Physiologic Mechanisms of Circadian Rhythms and Sleep/Wake Regulation through Mathematical Modeling.
J Biol Rhythms 2007; 22(3):233-245. [PMID: 17517913]

Indic P, Gurdziel K, Kronauer RE, Klerman EB. Development of a Two-Dimension Manifold to Represent High Dimension Mathematical Models of the Intracellular Mammalian Circadian Clock.
J Biol Rhythms 2006; 21(3):222-232. [PMID: 16731662]

Mochizuki T, Klerman EB, Sakurai T, Scammell T. Elevated body temperature during sleep in orexin knockout mice.
Am. J. Physiology: Regulatory, Integrative and Comparative Physiology 2006 Sep;291(3):R533-40. [PMID 16556901]

Indic P, Gurdziel K, Kronauer RE, Klerman EB. Development of a two-dimension manifold to represent high dimension mathematical models of the intra-cellular mammalian circadian clock.
J. Biol. Rhythms 2006 Jun;21(3):222-32.

Klerman EB. Clinical Aspects of Human Circadian Rhythms.
J. Biol. Rhythms. 2005; 20:375-386. [PMID 16077156]

Klerman EB, Dijk D-J. Inter-individual variation in sleep duration and its association with sleep debt in young adults.
Sleep. 2005;28:1253-1259. [PMID 16295210] Note: selected for editorial.

Indic P, Forger DB, St. Hilaire MA, Dean DA II, Brown EN, Kronauer RE, Klerman EB, Jewett ME. Comparison of amplitude recovery dynamics of two limit cycle oscillator models of the human circadian pacemaker.
Chronobiology International 2005; 22:613-629. [PMID 16147894]

Klerman EB, Davis B, Duffy JF, Dijk D-J, Kronauer RE. Older people awaken more frequently but fall back asleep at the same rate as younger people.
Sleep 2004:27:793-798. [PMID 15283016]
Klerman EB, Adler GK, Jin M, Maliszewski AM, Brown EN. A statistical model of diurnal variation in human growth hormone.
Am. J. Physiol. Endocrinol. Metab. 2003: 285:E1118-E1126. [PMID 12888486]

Klerman EB, Shanahan TL, Brotman DJ, Rimmer DW, Emens JS, Czeisler CA. Photic resetting of the human circadian pacemaker in the absence of conscious vision.
J. Biol. Rhythms 2002:17:548-555. [PMID 12465888]

Klerman EB, Gershengorn HB, Duffy JK, Kronauer RE. Comparisons of the variability of three markers of the human circadian pacemaker.
J. Biol. Rhythms. 2002;17:181-193. [PMID 12002165]

Klerman EB. Non-photic effects on the circadian system: results from experiments in blind and sighted individuals.
In Zeitgebers, Entrainment and Masking of the Circadian System, K. Honma and S. Honma (eds.). Sapporo 2001; pp155-169.

Duffy JF, Zeitzer JM, Rimmer DW, Klerman EB, Dijk D-J, Czeisler CA. Peak of circadian melatonin rhythm occurs later within the sleep of older subjects.
Am. J. Physiol. 2001; 282:E297-E303. [PMID 11788360]

Klerman EB, Zeitzer JM, Duffy JD, Khalsa SBS, Czeisler CA. Absence of an increase in the duration of the circadian melatonin secretory episode in totally blind human subjects.
J Clin Endocrinol Metab. 2001; 86:3166-70. [PMID 11443183]

Klerman EB, Goldenberg DL, Brown EN, Maliszewski AM, Adler GK. Circadian rhythms of women with fibromyalgia.
J. Clin. Endocrinol. Metab. 2001; 86:1034-1039. [PMID 11217145]

Klerman EB, Duffy JF, Dijk D-J, Czeisler CA. Circadian phase resetting in older people by ocular bright light exposure.
J. Invest. Med 2001; 49:30-40. [PMID 11238482]

Klerman EB, Boulos Z, Edgar DM, Mistlberger RE, Moore-Ede MC. EEG Delta Activity During Undisturbed Sleep in the Squirrel Monkey.
Sleep Research Online 2000; 3:113-119. [PMID 11382909]

Czeisler CA, Klerman EB. Circadian and Sleep-Dependent Regulation of Hormone Release in Humans.
Recent Progress in Hormone Research. 1999; 54:97-132. [PMID 10548874]

Klerman EB, Jewett ME. Com
mentary: Model Building, Quantitative Testing, and Model Comparison.
J. Biol. Rhythms.1999; 14: 621-624. [PMID 10643761]

Zeitzer, JM, Daniels JE, Duffy JF, Klerman EB, Shanahan TL, Dijk DJ, Czeisler CA. Do plasma melatonin concentrations decline with age?
Am. J. Medicine 1999; 107:432-436. [PMID 10569297]

Klerman EB, Lee YS, Czeisler CA, Kronauer RE. Linear demasking techniques are unreliable for estimating the circadian phase of ambulatory temperature data.
J. Biol. Rhythms.1999; 14:260-274. [PMID 10447306]

Klerman EB, Boulos Z, Edgar DM, Mistlberger RE, Moore-Ede MC. Circadian and homeostatic influences on sleep in the squirrel monkey: sleep after sleep deprivation.
Sleep, 1999; 22:45-59. [PMID 9989365]

Duffy JF, Dijk DJ, Klerman EB, Czeisler CA. Later endogenous circadian temperature nadir relative to an earlier wake time in older people.
Am. J. Physiol., 1998; 275: R1478-R1487. [PMID 9791064]

Klerman EB, Rimmer DW, Dijk DJ, Kronauer RE, Rizzo JF III, Czeisler CA. Nonphotic entrainment of the human circadian pacemaker.
Am. J. Physiol., 1998; 274: R991-R996. [PMID 9575961]

Jewett ME, Rimmer DW, Duffy JF, Klerman EB, Kronauer RE, Czeisler CA. Human circadian pacemaker is sensitive to light throughout the subjective day without evidence of transients.
Am. J. Physiol., 1997; 273:R1800-R1809. [PMID 9374826]

El-Hajj Fuleihan G, Klerman EB, Brown EN, Choe Y, Brown EM, Czeisler, CA. The parathyroid hormone circadian rhythm is truly endogenous - a General Clinical Research Center Study.
J. Clin. Endocrinol. Metab., 1997; 82: 281-286. [PMID 8989274]

Klerman EB, Dijk DJ, Kronauer RE, Czeisler, CA. Simulations of light effects on the human circadian pacemaker: implication for assessment of intrinsic period.
Am. J. Physiol, 1996; 270: R271-R282. [PMID 8769811]

Czeisler CA, Shanahan TL, Klerman EB, Martens H, Brotman DJ, Emens JS, Klein T, Rizzo JF III. Suppression of melatonin secretion in some blind patients by exposure to bright light.
New Engl. J. Med., 1995; 332:6-11. [PMID 7990870]

Proceedings of Meetings
Citi L, Bianchi MT, Klerman EB, Barbieri R. Instantaneous Monitoring of Sleep Fragmentation by Point Process Heart Rate Variability and Respiratory Dynamics.
IEEE Engineering in Medicine and Biology 2011 (in press).

Citi L, Klerman EB, Brown EN, Barbieri R. Point Process Heart Rate Variability Assessment during Sleep Deprivation.
Computers in Cardiology. 2010; 37:721-724.

Benloucif S, Burgess HJ, Klerman EB, Lewy AJ, Middleton B, Murphy PJ, Parry, BL, Revell VL. Measuring Melatonin in Humans.
Journal of Clinical Sleep Medicine 2008; 4:66-69. [PMID 18350967]

Dean II DA, Fletcher A, Hursh SR, Klerman EB. Developing Mathematical Models of Neurobehavioral Performance for the “Real World”
J. Biol. Rhythms. 2007; 22:246-258. [PMID 17517914]

Kronauer RE, Gunzelmann G, Van Dongen HPA, Doyle III FJ, Klerman EB. Uncovering Physiologic Mechanisms of Circadian Rhythms and Sleep/Wake Regulation through Mathematical Modeling.
J. Biol. Rhythms. 2007; 22:233-245.[PMID 17517913]

Klerman EB. Non-photic effects on the circadian system: results from experiments in blind and sighted individuals.
In K. Honma and S. Honma, eds. Zeitgebers, Entrainment and Masking of the Circadian System, Sapporo: Hokkaido University Press. 2001; pp155-169.

Klerman EB, Jewett ME. Commentary: Model Building, Quantitative Testing, and Model Comparison.
J. Biol. Rhythms.1999; 14: 621-624.[PMID 10643761]

Reviews, Chapters, and Editorials
Klerman EB and Bianchi, MT. Methods for Human Sleep Deprivation Experiments (in: Sleep Deprivation and Disease; Springer Publishers, Ed: Matt T. Bianchi), New York 2013.pp27-32

Alameddine Y, Klerman EB and Bianchi, MT. Caffeine and Naps as Countermeasures for Sleep Loss (in: Sleep Deprivation and Disease, Springer Publishers, Ed: Matt T. Bianchi), New York 2013.pp231-268.

Gronfier C, Klerman EB. Sleep - Endocrine changes. In: Binder, M.D, Hirokawa, N, Windhorst, U (eds).
Encyclopedia of Neuroscience. Springer, Berlin Heidelberg New York 2009 pp3710-3714.

Klerman EB. St. Hilaire M. On mathematical modeling of circadian rhythms, performance and alertness.
J. Biol. Rhythms. 2007 22:91-102. [PMID 17440211]

Klerman EB. Selective NREM Sleep Deprivation. In Carskadon MA, editor. Encyclopedia of Sleep and Dreaming. New York: Macmillan Inc., 1993. p. 177-178.
Klerman EB. Clinical Aspects of Human Circadian Rhythms.
J. Biol. Rhythms. 2005; 20:375-386.[PMID 16077156]

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