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keywords circadian rhythms
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Academic Background

B.S., Michigan State University1981
Ph.D., Michigan State University1985
Postdoctoral Research Fellow, Mass. General Hospital1985-1987
Postdoctoral Research Fellow, Harvard Medical School1985-1987
Assistant in Neurobiology, Massachusetts General Hospital1987-1992
Instructor, Harvard Medical School1987-1989
Assistant Professor, Harvard Medical School1989-1994
Associate Neurobiologist, Massachusetts General Hospital1993-2001
Associate Professor, Harvard Medical School1994-2001
Associate Professor, UMass Chan Medical School2001-2006
Director, Graduate Program in Neuroscience, UMass Chan Medical School2005-
Professor, UMass Chan Medical School2006-

 

Research Program Description: Molecular Physiology of Circadian Rhythms

The major objective of our research program is to understand the molecular mechanisms for circadian rhythmicity, and the impact of circadian rhythms on physiology and behavior.

Molecular mechanisms of circadian rhythmicity.

Daily rhythms in activity levels, alertness/sleep, body temperature, and hormonal profiles will persist in constant conditions, with a cycle length of about 24 hours, demonstrating the presence of an internal time-keeping system. When exposed to a daily light-dark cycle, these rhythms are synchronized (entrained) to a 24-hour period. In mammals, a small area of the anterior hypothalamus called the suprachiasmatic nucleus (SCN) is the principal circadian pacemaker (for review see Weaver, 1998; Reppert & Weaver 2001).

How do SCN neurons measure out 24 hours? Work on the circadian clocks of species ranging from bacteria to fungi to fruit flies has revealed a common thread, that the molecular basis for circadian rhythmicity is the rhythmic synthesis of "clock" molecules. In each of these species, and in mammals, molecules are synthesized rhythmically, and these molecules then feed back to turn off their own synthesis. This forms what is called a "transcriptional-translational feedback loop." Mutations of specific genes within the feedback loop result in altered or disrupted rhythmicity. Recently, great advances have been made in identifying the components of the circadian feedback loop in mammals, and in defining the specific roles of individual gene products in the circadian clock (reviewed in Reppert & Weaver 2002). The aim of this research is to understand the molecular mechanisms underlying generation and entrainment of circadian rhythms in mammals.

Current Research Projects:

We are studying behavioral and molecular phenotypes of mice with genetic defects altering circadian behavior. Other areas of interest are to identify the effects of clock gene mutations on other behavioral and physiological processes and to understand the importance of local oscillators in tissues outside the brain.

Please use the Publications Tab at the top of this page for the most up-to-date description of this research program and my collaborators.

 

 

One or more keywords matched the following items that are connected to Weaver, David
Item TypeName
Academic Article Definition of the developmental transition from dopaminergic to photic regulation of c-fos gene expression in the rat suprachiasmatic nucleus.
Academic Article Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock.
Academic Article Two period homologs: circadian expression and photic regulation in the suprachiasmatic nuclei.
Academic Article The suprachiasmatic nucleus: a 25-year retrospective.
Academic Article Interacting molecular loops in the mammalian circadian clock.
Academic Article The roles of melatonin in development.
Academic Article Nature's knockout: the Mel1b receptor is not necessary for reproductive and circadian responses to melatonin in Siberian hamsters.
Academic Article Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock.
Academic Article Forward genetic approach strikes gold: cloning of a mammalian clock gene.
Academic Article Cellular construction of a circadian clock: period determination in the suprachiasmatic nuclei.
Academic Article Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus.
Academic Article Three period homologs in mammals: differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain.
Academic Article Light-induced phase shifts in mice lacking mPER1 or mPER2.
Academic Article Light does not degrade the constitutively expressed BMAL1 protein in the mouse suprachiasmatic nucleus.
Academic Article Circadian and developmental regulation of Oct-2 gene expression in the suprachiasmatic nuclei.
Academic Article A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock.
Academic Article Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock.
Academic Article Photic induction of Period gene expression is reduced in Clock mutant mice.
Academic Article Differential regulation of mPER1 and mTIM proteins in the mouse suprachiasmatic nuclei: new insights into a core clock mechanism.
Academic Article Melatonin plays a crucial role in the regulation of rhythmic clock gene expression in the mouse pars tuberalis.
Academic Article Rhythms in clock proteins in the mouse pars tuberalis depend on MT1 melatonin receptor signalling.
Academic Article Peripheral gene expression rhythms in a diurnal rodent.
Academic Article Analysis of clock proteins in mouse SCN demonstrates phylogenetic divergence of the circadian clockwork and resetting mechanisms.
Academic Article The polycomb group protein EZH2 is required for mammalian circadian clock function.
Academic Article A time-less function for mouse timeless.
Academic Article Targeted disruption of the mPer3 gene: subtle effects on circadian clock function.
Academic Article Comparing clockworks: mouse versus fly.
Academic Article Molecular analysis of mammalian circadian rhythms.
Academic Article Peripheral circadian oscillators require CLOCK.
Academic Article Deletion of the secretory vesicle proteins IA-2 and IA-2beta disrupts circadian rhythms of cardiovascular and physical activity.
Academic Article Rhythmic gene expression in pituitary depends on heterologous sensitization by the neurohormone melatonin.
Academic Article Casein kinase 1 delta (CK1delta) regulates period length of the mouse suprachiasmatic circadian clock in vitro.
Academic Article The period of the circadian oscillator is primarily determined by the balance between casein kinase 1 and protein phosphatase 1.
Academic Article Distinct patterns of Period gene expression in the suprachiasmatic nucleus underlie circadian clock photoentrainment by advances or delays.
Academic Article Integrative gene regulatory network analysis reveals light-induced regional gene expression phase shift programs in the mouse suprachiasmatic nucleus.
Academic Article Disruption of gene expression rhythms in mice lacking secretory vesicle proteins IA-2 and IA-2?.
Academic Article Mammalian melatonin receptors: molecular biology and signal transduction.
Academic Article Coordination of circadian timing in mammals.
Academic Article Maternal communication of circadian phase to the developing mammal.
Academic Article Maternal-fetal communication of circadian phase in a precocious rodent, the spiny mouse.
Academic Article The circadian-gated timing of birth in rats: disruption by maternal SCN lesions or by removal of the fetal brain.
Academic Article Development and validation of computational models for mammalian circadian oscillators.
Academic Article Sleep rhythmicity and homeostasis in mice with targeted disruption of mPeriod genes.
Academic Article c-fos and jun-B mRNAs are transiently expressed in fetal rodent suprachiasmatic nucleus following dopaminergic stimulation.
Academic Article Entrainment of the fetal hamster circadian pacemaker by prenatal injections of the dopamine agonist SKF 38393.
Academic Article Melatonin receptors in human hypothalamus and pituitary: implications for circadian and reproductive responses to melatonin.
Academic Article Analysis of the prokineticin 2 system in a diurnal rodent, the unstriped Nile grass rat (Arvicanthis niloticus).
Academic Article A clock shock: mouse CLOCK is not required for circadian oscillator function.
Academic Article PER1-like immunoreactivity in oxytocin cells of the hamster hypothalamo-neurohypophyseal system.
Academic Article Transient, light-induced rhythmicity in mPer-deficient mice.
Academic Article CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock.
Academic Article Rhythmic expression of clock genes in the ependymal cell layer of the third ventricle of rodents is independent of melatonin signaling.
Academic Article Vascular rhythms and adaptation: do your arteries know what time it is?
Academic Article Casein kinase 1 delta regulates the pace of the mammalian circadian clock.
Academic Article The circadian clock protein Period 1 regulates expression of the renal epithelial sodium channel in mice.
Academic Article Altered body mass regulation in male mPeriod mutant mice on high-fat diet.
Academic Article Disrupting the circadian clock: gene-specific effects on aging, cancer, and other phenotypes.
Academic Article Periodic feeding of SCN-lesioned pregnant rats entrains the fetal biological clock.
Academic Article Direct in utero perception of light by the mammalian fetus.
Academic Article Photic resetting and entrainment in CLOCK-deficient mice.
Concept Circadian Rhythm
Concept Sleep Disorders, Circadian Rhythm
Academic Article Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration.
Academic Article The hepatic circadian clock modulates xenobiotic metabolism in mice.
Academic Article In: Circadian Clocks: Role in Health and Disease (M.L. Gumz, ed.)
Academic Article Clocks and meals keep mice from being cool.
Academic Article Functionally Complete Excision of Conditional Alleles in the Mouse Suprachiasmatic Nucleus by Vgat-ires-Cre.
Academic Article Desynchrony between brain and peripheral clocks caused by CK1d/e disruption in GABA neurons does not lead to adverse metabolic outcomes.
Academic Article Periodic Parasites and Daily Host Rhythms.
Academic Article Deconstructing circadian disruption: Assessing the contribution of reduced peripheral oscillator amplitude on obesity and glucose intolerance in mice.
Academic Article Methods for Detecting PER2:LUCIFERASE Bioluminescence Rhythms in Freely Moving Mice.
Academic Article Cell-Type-Specific Circadian Bioluminescence Rhythms in Dbp Reporter Mice.
Academic Article The Suprachiasmatic Nucleus at 50: Looking Back, Then Looking Forward.
Academic Article Circadian rhythms and the light-dark cycle interact to regulate amyloid plaque accumulation and tau phosphorylation in 5xFAD mice.
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  • circadian rhythms