Faculty Profile

Charles J. Weitz, MD, PhD

Charles J. Weitz, MD, PhD
Robert Henry Pfeiffer Professor of Neurobiology, Harvard Medical School

See publications


Inter-office Mail Address

Department of Neurobiology
Harvard Medical School
220 Longwood Ave.
Boston, MA 02115

Phone 617-432-0322

Email cweitz@hms.harvard.edu

Research Interests

We study the molecular biology and genetics of circadian clocks, endogenous oscillators that drive daily rhythms in behavior and physiology. Under natural conditions, circadian clocks become synchronized, or entrained, to the 24-hour light-dark cycle by the action of light on circadian photoreceptors. Together the intrinsic rhythms of the circadian clock and its entrainment to light-dark cycles control the temporal organization of complex behavioral and metabolic programs. In mammals, the master circadian clock regulating behavior is located in the suprachiasmatic nucleus (SCN) of the brain. Recently it has become clear that other brain sites and many peripheral tissues contain circadian clocks, but their physiological functions and relationships to the SCN are poorly understood.

A general picture of how circadian clocks are built has emerged in recent years from studies of the first handful of clock genes to be cloned. The core mechanism is a transcriptional feedback loop, wherein the products of several clock genes cooperate to inhibit the transcription factors responsible for their own activation. The molecular components of circadian clocks are conserved across virtually all animal species.

We use molecular biology, biochemistry, and genetics to investigate the mammalian circadian system. The focus of our efforts has been to identify and characterize molecular components of circadian clocks and to identify molecular pathways by which the central circadian clock in the SCN drives daily rhythms of behavior. We have also embarked on a major genetic analysis of the physiological functions of circadian clocks other than that of the SCN, including those elsewhere in the brain, the retina, and peripheral tissues.

Trainees

Fiona Watson, MS, 1993-1994
Katrin Chua, 1993-1996
Mary E. Sabatini Morris, MD, PhD, 1993-1997
Edmund Griffin, MD¸1998-2002
Sebastian Kraves, PhD, 2001-2006
Carlos F. Paz, 2001-2005
Nick Gekakis, ScD, 1993-1997
David J. Staknis, PhD, 1995-2001
Wen-Ning Zhao, PhD, 1998-2000
Achim Kramer, MD, PhD, 1999-2001
Nikolay L. Malinin, PhD, 1999-2001
Kai-Florian Storch, PhD, 2000-2008
Fu-Chia Yang, PhD, 2000-2006
D. Knutti, PhD, 2003-2007
M. Robles, PhD, 2003-2007
K. Lamia, PhD, 2004-2007
Cyril Boyault, PhD, 2007-2010
Leigh Amanda Sadacca, 2005-2010
Laura Lande-Diner, PhD, 2007-2009
Kiran Padmanabhan, PhD, 2006-present
Hao Doung, PhD, 2007-present
Alfred Tamayo, PhD, 2009-present
Jinyoung Kim, PhD, 2010-present
Andrew Delemos, MD, 2010-present

Research Funding

R01 NS060860-01  (PI: C Weitz)        6/1/2008-5/31/2013
National Institute of Neurological Disorders and Stroke
Circadian Clock of the Paraventricular Nucleus
To characterize the importance of the hypothalamic nucleus circadian clock in the regulation of feeding behavior and energy balance.

Mathers Foundation Award (PI: C Weitz)     10/1/2008-9/30/2011
G. Harold & Leila Y. Mathers Charitable Foundation
PERIOD protein complexes of the mammalian circadian clock
Identification and characterization of presently unknown proteins physically associated with PERIOD-1 and/or PERIOD-2, core components of the mammalian circadian clock mechanism.

R01GM095945 (PI: C Weitz)          9/1/2011- 7/31/2015
National Institute of General Medical Sciences                
BMAL1 complexes of the mammalian circadian clock
The major goal of this project is to identify currently unknown protein components of BMAL1 protein complexes and to determine if they play a fundamental role in the mammalian circadian clock.

R01 NS055831  (PI: C Weitz)        6/1/2006-5/31/2011
National Institute of Neurological Disorders and Stroke
Circadian Clock Regulation of the Mammalian Retina  
To characterize the molecular pathways controlled by the intrinsic circadian clock of the mammalian retina and to determine its physiological significance for retinal function.

Neuroscience of Brain Disorders Award  (PI: C Weitz)     2/1/2007-1/31/2011
McKnight Endowment Fund for Neuroscience
Diabetes, obesity, and the circadian clock of the arcuate nucleus
To characterize the role of the arcuate nucleus circadian clock in systemic glucose homeostasis and energy metabolism.

R21 EY017924  (PI: C Weitz)    9/1/2007-8/31/2009
National Eye Institute
Diurnal Rhythms of Gene Expression in the Anterior Eye

Teaching

Course Director, Neurobiology 221, “Molecular Neurobiology” (a core course in the Ph.D. Program in Neuroscience, Division of Medical Sciences, Harvard University)

Guest Lecturer, Molecular and Cellular Biology 186, “Circadian Biology:  from cellular oscillators to sleep regulation” (Harvard College).

Selected Publications

Duong HA, Robles MS, Knutti D, Weitz CJ. A molecular mechanism for circadian clock negative feedback.
Science. 2011 Jun 17;332(6036):1436-9. [PMID: 21680841]

Sadacca LA, Lamia KA, deLemos AS, Blum B, Weitz CJ. An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice.
Diabetologia. 2011 Jan;54(1):120-4. Epub 2010 Oct 3. [PMID: 20890745]

Robles MS, Boyault C, Knutti D, Padmanabhan K, Weitz CJ. Identification of RACK1 and protein kinase Calpha as integral components of the mammalian circadian clock.
Science. 2010 Jan 22;327(5964):463-6. [PMID: 20093473]

Smith RS, Weitz CJ, Araneda RC. Excitatory actions of noradrenaline and metabotropic glutamate receptor activation in granule cells of the accessory olfactory bulb.
J Neurophysiol. 2009 Aug;102(2):1103-14. Epub 2009 May 27. [PMID: 19474170]

Storch KF, Weitz CJ. Daily rhythms of food-anticipatory behavioral activity do not require the known circadian clock.
Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6808-13. Epub 2009 Apr 6. [PMID: 19366674]

Lamia KA, Storch KF, Weitz CJ. Physiological significance of a peripheral tissue circadian clock.
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15172-7. Epub 2008 Sep 8. [PMID: 18779586]

Storch KF, Paz C, Signorovitch J, Raviola E, Pawlyk B, Li T, Weitz CJ. Intrinsic circadian clock of the mammalian retina: importance for retinal processing of visual information.
Cell. 2007 Aug 24;130(4):730-41. [PMID:17719549]

Zhao WN, Malinin N, Yang FC, Staknis D, Gekakis N, Maier B, Reischl S, Kramer A, Weitz CJ. CIPC is a mammalian circadian clock protein without invertebrate homologues.
Nat Cell Biol. 2007 Mar;9(3):268-75. Epub 2007 Feb 18. [PMID: 17310242]

Storch KF, Paz C, Signorovitch J, Raviola E, Pawlyk B, Li T, Weitz CJ. Physiological importance of a circadian clock outside the suprachiasmatic nucleus.
Cold Spring Harb Symp Quant Biol. 2007;72:307-18. [PMID: 18419288]

Zhou Z, Hong EJ, Cohen S, Zhao WN, Ho HY, Schmidt L, Chen WG, Lin Y, Savner E, Griffith EC, Hu L, Steen JA, Weitz CJ, Greenberg ME. Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation.
Neuron. 2006 Oct 19;52(2):255-69. [PMID: 17046689]

Kraves S, Weitz CJ. A role for cardiotrophin-like cytokine in the circadian control of mammalian locomotor activity. Nat Neurosci. 2006 Feb;9(2):212-9. Epub 2006 Jan 22. [PMID: 16429135]

Kramer A, Yang FC, Kraves S, Weitz CJ. A screen for secreted factors of the suprachiasmatic nucleus.
Methods Enzymol. 2005;393:645-63. [PMID: 15817317]

Zhong S, Storch KF, Lipan O, Kao MC, Weitz CJ, Wong WH. GoSurfer: a graphical
interactive tool for comparative analysis of large gene sets in Gene Ontology space.
Appl Bioinformatics. 2004;3(4):261-4. [PMID: 15702958]

Storch KF, Lipan O, Leykin I, Viswanathan N, Davis FC, Wong WH, Weitz CJ. Extensive and divergent circadian gene expression in liver and heart.
Nature. 2002 May 2;417(6884):78-83. Epub 2002 Apr 21. Erratum in: Nature 2002 Aug 8;418(6898):665. [PMID: 11967526]

RIKEN Genome Exploration Research Group Phase II Team and the FANTOM Consortium. Functional annotation of a full-length mouse cDNA collection.
Nature. 2001 Feb 8;409(6821):685-90. [PMID: 11217851]

Kramer A, Yang FC, Snodgrass P, Li X, Scammell TE, Davis FC, Weitz CJ. Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signaling.
Science. 2001 Dec 21;294(5551):2511-5. [PMID: 11752569]

Griffin EA Jr, Staknis D, Weitz CJ. Light-independent role of CRY1 and CRY2 in the mammalian circadian clock.
Science. 1999 Oct 22;286(5440):768-71. PubMed PMID: 10531061]

Ceriani MF, Darlington TK, Staknis D, Más P, Petti AA, Weitz CJ, Kay SA. Light-dependent sequestration of Timeless by Cryptochrome.
Science. 1999 Jul 23;285(5427):553-6. [PMID: 10417378]

Sangoram AM, Saez L, Antoch MP, Gekakis N, Staknis D, Whiteley A, Fruechte EM, Vitaterna MH, Shimomura K, King DP, Young MW, Weitz CJ, Takahashi JS. Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription.
Neuron. 1998 Nov;21(5):1101-13. [PMID: 9856465]

Gekakis N, Staknis D, Nguyen HB, Davis FC, Wilsbacher LD, King DP, Takahashi JS, Weitz CJ. Role of the CLOCK protein in the mammalian circadian mechanism.
Science. 1998 Jun 5;280(5369):1564-9. [PMID: 9616112]

Darlington TK, Wager-Smith K, Ceriani MF, Staknis D, Gekakis N, Steeves TD, Weitz CJ, Takahashi JS, Kay SA. Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim.
Science. 1998 Jun 5;280(5369):1599-603. [PMID: 9616122]

Morris ME, Viswanathan N, Kuhlman S, Davis FC, Weitz CJ. A screen for genes induced in the suprachiasmatic nucleus by light.
Science. 1998 Mar 6;279(5356):1544-7. [PMID: 9488654]

Gekakis N, Saez L, Delahaye-Brown AM, Myers MP, Sehgal A, Young MW, Weitz CJ. Isolation of timeless by PER protein interaction: defective interaction between timeless protein and long-period mutant PERL.
Science. 1995 Nov 3;270(5237):811-5. [PMID: 7481773]

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