Division of Sleep Medicine @ Harvard Medical School
Faculty Profile
Elizabeth B. Klerman, MD, PhD
Associate Professor of Medicine, Harvard Medical School
Associate Physician, Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital
Administrative Title(s)
Associate Director, BWH Clinical Translational Science Center
Address
221 Longwood Avenue, Suite 438Boston, MA 02115
USA
Phone 617-732-5500 ext.33948
Fax 617-732-4015
Society Memberships
Sleep Research SocietySociety for Research in Biological Rhythms
Society for Mathematical Biology
Research Unit(s)
Analytic and Modeling Unit, Division of Sleep Medicine, 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.
(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
H.B. Gershengorn MD 1997-1998, 2000-2001
J.B. Davis MD 1999-2001
J.C. Kuhn, PhD 2000-2001
P. Indic PhD 2003-2004
D A Dean II (in PhD program) 2004-present
M St. Hilaire (in PhD program) 2004-present
C. Diniz-Behn PhD 2006-2007
D Cohen MD 2006-2008
R Torgovitsky 2007-2008
S Krishnamachari PhD 2008-present
J.B. Davis MD 1999-2001
J.C. Kuhn, PhD 2000-2001
P. Indic PhD 2003-2004
D A Dean II (in PhD program) 2004-present
M St. Hilaire (in PhD program) 2004-present
C. Diniz-Behn PhD 2006-2007
D Cohen MD 2006-2008
R Torgovitsky 2007-2008
S Krishnamachari PhD 2008-present
Mentor(s)
Charles A. Czeisler, PhD, MD
Gordon H. Williams, MD
Janet E. Hall, MD
Joanne Ingwall, PhD
Ellen Seely, MD
Gordon H. Williams, MD
Janet E. Hall, MD
Joanne Ingwall, PhD
Ellen Seely, MD
Research Funding
NICHD/NIH, P.I.:"Impact of Sleep Disruption on Menstrual Cycle Dynamics"
NSBRI, P.I. HFP01604: "Designing Individual Countermeasures to Reduce Sleep Disruption and Improve Performance and Alertness in Space"
NIH NIA, P.I. on Analytic Core within Program Project Grant. 2P01-AG009975: "Sleep, Aging, and Circadian Rhythm Disorders" (C.A. Czeisler PhD MD, P.I.)
NSBRI, P.I. HFP01701. Associate Team Leader: "Human Factors and Performance Team"
(NICHD)/NIH, P.I. on subcontract for "Circadian Rhythms and Sleep"
R01-HD015788: "Neuroendocrine Control of Reproduction in the Human" (W. F. Crowley Jr. MD, P.I.)
NSBRI, P.I. HFP01604: "Designing Individual Countermeasures to Reduce Sleep Disruption and Improve Performance and Alertness in Space"
NIH NIA, P.I. on Analytic Core within Program Project Grant. 2P01-AG009975: "Sleep, Aging, and Circadian Rhythm Disorders" (C.A. Czeisler PhD MD, P.I.)
NSBRI, P.I. HFP01701. Associate Team Leader: "Human Factors and Performance Team"
(NICHD)/NIH, P.I. on subcontract for "Circadian Rhythms and Sleep"
R01-HD015788: "Neuroendocrine Control of Reproduction in the Human" (W. F. Crowley Jr. MD, P.I.)
Selected Publications
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]
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, Klerman EB, Khalsa SBS, Wright, Jr. KP, Czeisler CA, Kronauer RE. Addition of a non-photic component to a light-based mathematical model of the human circadian pacemaker.
Journal of Theoretical Biology. 2007; 247:583-599. [PMID 17531270]
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]
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]
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, Klerman EB, Khalsa SBS, Wright, Jr. KP, Czeisler CA, Kronauer RE. Addition of a non-photic component to a light-based mathematical model of the human circadian pacemaker.
Journal of Theoretical Biology. 2007; 247:583-599. [PMID 17531270]
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]
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