Faculty Profile

Thomas E. Scammell, MD

Thomas E. Scammell, MD
Professor of Neurology, Harvard Medical School
Physician, Associate Professor, Department of Neurology, Beth Israel Deaconess Medical Center

See publications

Inter-office Mail Address

Center for Life Sciences, Room 705

Phone 617-667-3237

Society Memberships

American Academy of Sleep Medicine
Sleep Research Society
Society for Neuroscience
American Neurological Association

Research Unit(s)

Systems Neurobiology Group (Scammell), Beth Israel Deaconess Medical Center

Research Interests

Our research focuses on the neurobiology of narcolepsy. Narcolepsy is caused by destruction of the hypothalamic neurons that make the neuropeptides orexin/hypocretin. We have found that the orexin-producing neurons are active during wakefulness, and we have identified the numerous inputs to these cells. Now, we are identifying the critical pathways through which orexin promotes wakefulness and suppresses cataplexy. We have produced mice with inducible, focal expression of the orexin receptors. Using adeno-associated vectors and genetic approaches, we can induce eutopic expression of orexin receptors in neurochemically specific populations to identify which brain regions are essential for the wake-promoting effects of orexin. We also are studying the interactions of sleep and pain. Additional experiments use optogenetics and DREADDs to activate or inhibit specific neural pathways that regulate sleep and wakefulness. Through these experiments, we hope to gain a detailed understanding of the neurobiology of orexin that will result in highly effective therapies for patients with narcolepsy and enhance our knowledge of sleep.


Emily Ko, MD, 1999-2000
Thomas Jhou (Chou), PhD, 2000-2002
Scott P. Grady, MD, PhD, 2001-2002
Takatoshi Mochizuki, PhD, 2001-2006
Rodrigo A. España, PhD, 2003-2005
Kyoko Yoshida, PhD, 2003-2005
Agnieszka M. Janisiewicz, 2005-2005
Sandor Kantor, PhD, 2005-2009
Cecilia Diniz-Behn, PhD, 2006-2007
Christian R. Bauman, MD, 2007-2008
Chloe Alexandre, PhD, 2007-present
Alisha Ling, BS, 2010-2011
Christian Burgess, BS, 2010-2012
Philipp Valko, MD, 2010-2012
Yo Oishi, PhD, 2010-present
Daniel Kroeger, PhD, 2011-present
Carrie Mahoney, PhD, 2012-present
Joel Geerling, 2013-present

Research Funding

Ongoing Research Support:

R01 DE022912 Woolf,Scammell (Co-PI’s)  7/1/12-6/30/17
“Sleep Disturbance as a Risk Factor for Developing Chronic Pain”
The major goal of this project is to examine how insufficient sleep and fragmented sleep contribute to the development of chronic pain after peripheral nerve injury in mice.
Role: Co-PI

R01 NS061863    Arrigoni (PI)        1/1/09-12/31/14
NIH/NINDS    “Pontine Control of REM Atonia”
The goal of this project is to define the physiology of REM sleep atonia neurons and to determine the mechanism for orexin effects on these neurons. The scope is to better understand the neurobiology of REM sleep behavior disorder and cataplexy.
Role: Collaborator

P01 HL095491      Saper (PI)    1/3/10-2/28/15
NIH/NHLBI    “Mechanisms of State Switching in Sleep and Sleep Apnea: Project 3”
The major goal of this project is to define the physiological and anatomical pathways through which the orexin neurons sustain wakefulness and trigger arousals from sleep driven by hypercapnia. An improved understanding of these pathways will provide crucial insights into the neurobiology of arousal, bringing us closer to more effective treatments for sleepiness and OSA.
Role: PI on Project 3

R43 NS077514 Gerashchenko (PI)    12/1/11-11/30/13  
“AAV-based toolkit for targeting specific cell types”
The major goal of this project is to develop an efficient and inexpensive toolkit for ablating or reversibly inactivating specific cell types in the brain or other organs of mammals.
Role: PI on Subcontract

Completed Research Support:

R01 NS055367       Scammell (PI)    12/1/00-4/30/12
NINDS    “Orexin and the Control of Cataplexy”
The major goals of this project are to determine whether mouse cataplexy is triggered by positive emotions, to define the neurochemical systems that control cataplexy, and to physiologically and anatomically identify the pathways through which orexin suppresses cataplexy.
Role: PI

R01 MH62589       Scammell (PI)    8/15/01-4/30/07
NIMH    “Circadian and Aminergic Regulation of Orexin Neurons”
 The major goals of this project were to identify the afferents to the orexin (hypocretin) neurons, to determine the pattern of activity in these neurons, and to study whether the orexin neurons play a critical role in the circadian regulation of sleep/wake behavior.
Role: PI

P50 HL60292     Scammell (Project PI)    9/1/03-8/31/08
NHLBI    “Harvard Center on the Neurobiology of Sleep and Sleep Apnea: Project 3”
The major goal of this project was to define the physiology and essential neural pathways that underlie the sleepiness of mice with impaired orexin signaling. Understanding these pathways provides crucial insights into the neurobiology of narcolepsy and other sleep disorders
Role: Project PI

Takeda Pharmaceuticals North America    Scammell (PI)    5/1/06-10/31/08
“Consolidation of sleep and wakefulness in narcoleptic mice by ramelteon”
The major goals of this project were to determine whether the orexin neurons are necessary for the sleep-consolidating effects of ramelteon and whether treatment with ramelteon could improve the daytime sleepiness of narcolepsy.
Role: PI


2000-2006 Narcolepsy Advances in the Treatment of Sleep Disorders, Harvard Medical School

2003-2007 Narcolepsy: Diagnosis and Neurobiology, and Narcolepsy: Pathology and Treatment
Advanced Sleep Medicine Course, American Academy of Sleep Medicine

2009-2011 Anatomy and Pharmacology of Wakefulness Basic Science of Sleep for the Sleep Specialist, Sleep Research Society

2009-2012Narcolepsy and Other Hypersomnias Board Review for the Sleep Specialist Course,
American Academy of Sleep Medicine

2007    CSB Distinguished Visiting Neuroscientist, University of Toronto
2009    Invited Special Lecture, Annual Meeting of the Associated Professional Sleep Societies
2010    Elected Alumnus Member, Alpha Omega Alpha

Selected Publications

Original Articles

Poli F, Overeem S, Lammers GJ, Plazzi G, Lecendreux M, Bassetti CL, Dauvilliers Y, Keene D, Khatami R, Li Y, Mayer G, Nohynek H, Pahud B, Paiva T, Partinen M, Scammell TE, Shimabukuro T, Sturkenboom M, van Dinther K, Wiznitzer M, Bonhoeffer J. Narcolepsy as an adverse event following immunization: Case definition and guidelines for data collection, analysis and presentation.
Vaccine. 2012 Dec 16. [PMID: 23246545]

Imbach LL, Werth E, Kallweit U, Sarnthein J, Scammell TE, Baumann CR. Inter-hemispheric oscillations in human sleep.
PLoS One. 2012;7(11):e48660. [PMID: 23144920]

Scott MM, Marcus JN, Pettersen A, Birnbaum SG, Mochizuki T, Scammell TE, Nestler EJ, Elmquist JK, Lutter M. Hcrtr1 and 2 signaling differentially regulates depression-like behaviors.
Behav Brain Res. 2011 Sep 23;222(2):289-94. [PMID: 21377495]

Dimitrova A, Fronczek R, Van der Ploeg J, Scammell T, Gautam S, Pascual-Leone A, Lammers GJ. Reward-seeking behavior in human narcolepsy.
J Clin Sleep Med. 2011 Jun 15;7(3):293-300. [PMID: 21677900]

Mochizuki T, Arrigoni E, Marcus JN, Clark EL, Yamamoto M, Honer M, Borroni E, Lowell BB, Elmquist JK, Scammell TE. Orexin receptor 2 expression in the posterior hypothalamus rescues sleepiness in narcoleptic mice.
Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4471-6. [PMID: 21368172]

Scammell TE, Matheson JK, Honda M, Thannickal TC, Siegel JM. Coexistence of narcolepsy and Alzheimer's disease.
Neurobiol Aging. 2011 Jan 21. [PMID: 21257235]

Diniz Behn CG, Klerman EB, Mochizuki T, Lin SC, Scammell TE. Abnormal sleep/wake dynamics in orexin knockout mice.
Sleep. 2010 Mar;33(3):297-306.  [PMID: 20337187]

Baumann CR, Bassetti CL, Valko PO, Haybaeck J, Keller M, Clark E, Stocker R, Tolnay M, Scammell TE. Loss of hypocretin (orexin) neurons with traumatic brain injury.
Ann Neurol. 2009 Oct;66(4):555-9. [PMID: 19847903]

Kantor S, Mochizuki T, Janisiewicz AM, Clark E, Nishino S, Scammell TE. Orexin neurons are necessary for the circadian control of REM sleep.
Sleep. 2009 Sep;32(9):1127-34. [PMID: 19750917]

Clark EL, Baumann CR, Cano G, Scammell TE, Mochizuki T. Feeding-elicited cataplexy in orexin knockout mice.
Neuroscience. 2009 Jul 21;161(4):970-7. Epub 2009 Apr 8. [PMID: 19362119]

Scammell TE, Willie JT, Guilleminault C, Siegel JM; International Working Group on Rodent Models of Narcolepsy. A consensus definition of cataplexy in mouse models of narcolepsy.
Sleep. 2009 Jan 1;32(1):111-6. [PMID: 19189786]

Diniz Behn CG, Kopell N, Brown EN, Mochizuki T, Scammell TE.  Delayed orexin signaling consolidates wakefulness and sleep: physiology and modeling.
J Neurophysiol. 2008 Jun;99(6):3090-103. [PMID: 18417630]

Baumann CR, Clark EL, Pedersen NP, Hecht JL, Scammell TE. Do enteric neurons make hypocretin?
Regul Pept. 2008 Apr 10;147(1-3):1-3. [PMID: 18191238 ]

España, R, McCormack, S, Mochizuki, T,  Scammell, TE. Running and the effects of running wheels in orexin knockout mice.
Sleep. 2007 Nov 1;30(11):1417-25. [PMID: 18041476]

Diniz Behn, C, Brown, EN, Scammell, TE, Kopell, N. A mathematical model of network dynamics governing mouse sleep-wake behavior.
J Neurophysiol. 2007 Jun;97(6):3828-40. Epub 2007 Apr 4. [PMID: 17409167]

Scammell TE, Saper CB. Orexins: looking forward to sleep, back at addiction.
Nat Med. 2007 Feb;13(2):126-8. [PMID: 17290266]

Mochizuki, M, Klerman, EB, Sakurai, T,  Scammell, TE. Elevated body temperature during sleep in orexin knockout mice.
Am J Physiol Regul Integr Comp Physiol. 2006 Sep;291(3):R533-40. [PMID: 16556901]

Grady, S, Nishino, S, Czeisler, C, Hepner, D,  Scammell, TE. Diurnal variation in CSF orexin-A in healthy male subjects.
Sleep. 2006 Mar 1;29(3):295-7. [PMID: 16553014]

Scammell TE. The frustrating and mostly fruitless search for an autoimmune cause of narcolepsy.
Sleep. 2006 May 1;29(5):601-2. [PMID: 16774147]

Yoshida K, McCormack S, Espana RA, Crocker A, and Scammell TE. Afferents to the orexin neurons of the rat brain.
J Comp Neurol. 2006 Feb 10;494(5):845-61. [PMID: 16374809]

Crocker, A, España, RA, Papadopoulou, M, Saper, CB, Faraco, J, Sakurai, T, Honda, M, Mignot, E, and Scammell, TE. Concomitant loss of dynorphin, NARP, and orexin in narcolepsy. Neurology. 2005 Oct 25;65(8):1184-8. Epub 2005 Sep 14. [PMID: 16247044]

Mochizuki T, Crocker A, McCormack S, Yanagisawa M, Sakurai T, and Scammell TE. Behavioral state instability in orexin knock-out mice.
J Neurosci. 2004 Jul 14;24(28):6291-300. [PMID: 15254084]

Scammell, TE, Thompson, MA, Saper, CB, and Greene, R. Focal deletion of the adenosine A1 receptor in adult mice using an adeno-associated viral vector.
J Neurosci. 2003 Jul 2;23(13):5762-70. [PMID: 12843280]

Estabrooke, IV, McCarthy, MT, Ko, E, Chou, T, Chemelli, R, Yanagisawa, M, Saper, CB, Scammell, TE. Fos expression in orexin neurons varies with behavioral state.
J Neurosci. 2001 Mar 1;21(5):1656-62. [PMID: 11222656]

Scammell, TE, Estabrooke, IV, McCarthy, MT, Chemelli, R, Yanagisawa, M, Miller, MS, and Saper, CB. Hypothalamic arousal regions are activated during modafinil-induced wakefulness.
J Neurosci. 2000 Nov 15;20(22):8620-8. [PMID: 11069971]

Chemelli, RM, Willie, JT, Sinton, CM, Elmquist, JK, Scammell, T, Lee, C, Richardson, JA, Williams, SC, Xiong, Y, Kisanuki, Y, Fitch, TE, Nakazato, M, Hammer, RE, Saper, CB, and Yanagisawa, M. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation.
Cell. 1999 Aug 20;98(4):437-51. [PMID: 10481909

Scammell, TE, Gerashchenko, D, Urade, Y, Onoe, H, Saper, C, Hayaishi, O. Activation of ventrolateral preoptic neurons by the somnogen prostaglandin D2.
Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7754-9. [PMID: 9636223]


Burgess CR, Scammell TE. Narcolepsy: neural mechanisms of sleepiness and cataplexy.
J Neurosci. 2012 Sep 5;32(36):12305-11. Review. [PMID: 22956821]

Saper CB, Romanovsky AA, Scammell TE. Neural circuitry engaged by prostaglandins during the sickness syndrome.
Nat Neurosci. 2012 Jul 26;15(8):1088-95. Review. [PMID: 22837039]

España RA, Scammell TE. Sleep neurobiology from a clinical perspective.
Sleep. 2011 Jul 1;34(7):845-58. Review. [PMID: 21731134]

Scammell TE, Winrow CJ. Orexin receptors: pharmacology and therapeutic opportunities.
Annu Rev Pharmacol Toxicol. 2011 Feb 10;51:243-66. Review. [PMID: 21034217]

Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE. Sleep state switching.
Neuron. 2010 Dec 22;68(6):1023-42. Review. [PMID: 21172606]

Arrigoni E, Mochizuki T, Scammell TE. Activation of the basal forebrain by the orexin/hypocretin neurones.
Acta Physiol (Oxf). 2010 Mar;198(3):223-35. Review. [PMID: 19723027]

Lim AS, Scammell TE. The trouble with Tribbles: do antibodies against TRIB2 cause narcolepsy?
Sleep. 2010 Jul;33(7):857-8. [PMID: 20614841]

Lammers GJ, Bassetti C, Billiard M, Black J, Broughton R, Dauvilliers Y, Ferini Strambi L, Garcia-Borreguero D, Goswami M, Högl B, Iranzo A, Jennum P, Khatami R, Lecendreux M, Mayer G, Mignot E, Montplaisir J, Nevsimalova S, Peraita-Adrados R, Plazzi G, Scammell T, Silber M, Sonka K, Tafti M, Thorpy M. Sodium oxybate is an effective and safe treatment for narcolepsy.
Sleep Med. 2010 Jan;11(1):105-6; author reply 106-8. [PMID: 19846338]

Scammell TE, Mochizuki T. Is low histamine a fundamental cause of sleepiness in narcolepsy and idiopathic hypersomnia?
 Sleep. 2009 Feb 1;32(2):133-4. [PMID: 19238797]

Baumann CR, Scammell TE, Bassetti CL. Parkinson's disease, sleepiness and hypocretin/orexin.
Brain. 2008 Mar;131(Pt 3):e91. [PMID: 17898005]

Saper, CB, Scammell, TE, and Lu, J. Hypothalamic regulation of sleep and circadian rhythms.
Nature. 2005 Oct 27;437(7063):1257-63. [PMID: 16251950]

Scammell, TE. The neurobiology, diagnosis, and treatment of narcolepsy.
Ann Neurol. 2003 Feb;53(2):154-66. [PMID: 12557281]

Saper, CB, Chou, TC and Scammell, TE. The sleep switch: hypothalamic control of sleep and wakefulness.
Trends Neurosci. 2001 Dec;24(12):726-31. [PMID: 11718878]

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