Faculty Profile

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.

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).

WN Zhao,  N Malinin,  FC Yang,  D Staknis,   N Gekakis,  CJ Weitz.  CIPC, a mammalian circadian clock protein without invertebrate homologs.
Nature Cell Biology (in press).

Z Zhou, EJ Hong, S Cohen, WN Zhao, HH Ho, L Schmidt, WG Chen, E Savner, EC Griffith, L Hu, JA J Steen, CJ Weitz, ME Greenberg.  Brain-specific phosphorylation of of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation.
Neuron 52, 255-69 (2006).

S Kraves & CJ Weitz.  A role for cardiotrophin-like cytokine in the circadian control of mammalian locomotor activity.  
Nature Neuroscience 9, 212-9 (2006).

S Zhong, KF Storch, O Lipan, MC Mao, CJ Weitz, WH Wong.  GoSurfer: A Graphical Interactive Tool For Comparative Analysis of Large Gene Sets in Gene Ontology Space.
Appl. Bioinformatics 3, 261-4 (2004).

KF Storch, O Lipan, I Leykin, N Viswanathan, FC Davis, WH Wong, CJ Weitz.  Extensive and divergent circadian gene expression in liver and heart. 
Nature 417, 78-83 (2002).

A Kramer, FC Yang, P Snodgrass, X Li, TE Scammell, FC Davis, CJ Weitz.  Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signaling (Research Article) Science 294, 2511-2515 (2001).

RIKEN Genome Exploration Research Group Phase II Team and the FANTOM Consortium*.  Functional annotation of a full-length mouse cDNA collection.   (Article) 
Nature 409, 685-690 (2001).   *C. J. Weitz one of six senior managers.

EA Griffin Jr, D Staknis, CJ Weitz.  Light-independent role for CRY1 and CRY2 in the mammalian circadian clock.  
Science 286, 768-771 (1999).

FCeriani, TK Darlington, D Staknis, P Mas, AA Petti, CJ Weitz, SA Kay.  Light-dependent sequestration of TIMELESS by CRYPTOCHROME. (Research Article)
Science 285, 553-556 (1999).

A Sangoram, L Saez, M Antoch, N Gekakis, D Staknis, A Whitely, E Freuchte, M Vitaterna, K Shimomura, D King, M Young, CJ Weitz, JS Takahashi.  Mammalian circadian autoregulatory loop:  a Timeless  ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription. 
Neuron 21, 1101-1113 (1998).

N Gekakis, DJ Staknis, HB Nguyen, FC Davis, LD Wilsbacher, DP King, JS Takahashi, CJ Weitz.  Role of the CLOCK protein in the mammalian circadian mechanism.  (Research Article) Science 280, 1564-1569 (1998).

TK Darlington, K Wager-Smith, M Ceriani, D Staknis, N Gekakis, T Steeves, CJ Weitz, J Takahashi, S Kay.  Closing the circadian loop:  CLOCK induced transcription of its own inhibitors,  period  and timeless.
Science 280, 1599-1603 (1998).

ME Morris, N Viswanathan, S Kuhlman, FC Davis, CJ Weitz.  A screen for genes induced in the suprachiasmatic nucleus by light. 
Science 279, 1544-1547 (1998).

N Gekakis, L Saez, AM Delahaye-Brown, MP Myers, A Sehgal, MW Young, CJ Weitz.  Isolation of timeless  by PER protein interaction:  defective interaction of timeless protein with long-period mutant PERL. 
Science 270, 811-815 (1995).