BBS Faculty Member - Charles Weitz

Charles Weitz

Department of Neurobiology

Harvard Medical School
Dept. of Neurobiology, WAB, Rm. 412
220 Longwood Avenue
Boston, MA 02115
Tel: 617-432-0322
Fax: 617-432-1369
Email: cweitz@hms.harvard.edu



We study the molecular biology and genetics of mammalian circadian clocks, intrinsic molecular oscillators that drive daily rhythms in physiology, metabolism, and behavior. The master circadian clocks regulating the sleep-wake cycle and daily rhythms of feeding behavior are located within specific clock cells in the hypothalamus of the brain. In recent years it has become clear that most or all peripheral tissues also contain intrinsic circadian clocks, and emerging evidence indicates that such clocks play important and broad roles in physiology and metabolism, including the regulation of circulating hormones, glucose, and lipids.

A general picture of how circadian clocks are built has emerged in recent years from genetic and biochemical studies. The core mechanism is a transcriptional feedback loop, highly conserved across all animal species, in which the protein products of several dedicated clock genes cooperate to inhibit the transcription factor responsible for their own expression. This feedback loop not only drives self-sustaining oscillations of the clock mechanism itself, but also drives daily rhythms of activation of a large number of genes involved in diverse aspects of cellular, tissue, and systemic physiology. It has become apparent that the clock mechanism is evolutionarily ancient and represents a fundamental biological timing mechanism operating at the level of single cells.

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, to identify molecular pathways by which central circadian clocks drive rhythms in behavioral activity, and to determine the physiological functions of clocks in various brain sites and tissues by conditional genetic studies in mice. Recently, we have developed a large-scale proteomics strategy to identify proteins acting in the core circadian clock mechanism, and our initial findings point to unanticipated actions of the core clock proteins in the generation of circadian rhythms.



Last Update: 8/22/2013



Publications

For a complete listing of publications click here.

 


 

Duong HA, Robles MS, Knutti K, Weitz CJ. A molecular mechanism for circadian clock negative feedback. Science 2011; 332: 1436-9.

Robles MS, Boyault C, Knutti D, Padmanabhan K, Weitz CJ. Identification of RACK1 and Protein Kinase C
a as integral components of the mammalian circadian clock. Science 2010; 327: 463-6.

Lamia KA, Storch K-F, Weitz CJ. Physiological significance of a peripheral tissue circadian clock.
Proc Natl Acad Sci USA 2008; 105: 15172-77.

Storch K-F, 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; 130: 730-41.



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