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Weaver, David

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overview

Academic Background

B.S., Michigan State University	1981
Ph.D., Michigan State University	1985
Postdoctoral Research Fellow, Mass. General Hospital	1985-1987
Postdoctoral Research Fellow, Harvard Medical School	1985-1987
Assistant in Neurobiology, Massachusetts General Hospital	1987-1992
Instructor, Harvard Medical School	1987-1989
Assistant Professor, Harvard Medical School	1989-1994
Associate Neurobiologist, Massachusetts General Hospital	1993-2001
Associate Professor, Harvard Medical School	1994-2001
Associate Professor, UMass Chan Medical School	2001-2006
Director, Graduate Program in Neuroscience, UMass Chan Medical School	2005-
Professor, UMass Chan Medical School	2006-

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 Type	Name
Academic Article	Definition of the developmental transition from dopaminergic to photic regulation of c-fos gene expression in the rat suprachiasmatic nucleus.
Academic Article	The Mel1a melatonin receptor gene is expressed in human suprachiasmatic nuclei.
Academic Article	D1-dopamine receptors activate c-fos expression in the fetal suprachiasmatic nuclei.
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	Melatonin limits transcriptional impact of phosphoCREB in the mouse SCN via the Mel1a receptor.
Academic Article	Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock.
Academic Article	Postmortem stability of melatonin receptor binding and clock-relevant mRNAs in mouse suprachiasmatic nucleus.
Academic Article	Forward genetic approach strikes gold: cloning of a mammalian clock gene.
Academic Article	Distinct pharmacological mechanisms leading to c-fos gene expression in the fetal suprachiasmatic nucleus.
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	Molecular analysis of mammalian timeless.
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	Expression of basic helix-loop-helix/PAS genes in the mouse suprachiasmatic nucleus.
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	mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop.
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	Analysis of clock proteins in mouse SCN demonstrates phylogenetic divergence of the circadian clockwork and resetting mechanisms.
Academic Article	A time-less function for mouse timeless.
Academic Article	Comparing clockworks: mouse versus fly.
Academic Article	Molecular analysis of mammalian circadian rhythms.
Academic Article	Loss of responsiveness to melatonin in the aging mouse suprachiasmatic nucleus.
Academic Article	Deletion of the secretory vesicle proteins IA-2 and IA-2beta disrupts circadian rhythms of cardiovascular and physical activity.
Academic Article	Casein kinase 1 delta (CK1delta) regulates period length of the mouse suprachiasmatic circadian clock in vitro.
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	Targeted disruption of the mouse Mel(1b) melatonin receptor.
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	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	Serotonin receptor gene expression in the rat suprachiasmatic nuclei.
Academic Article	A clock shock: mouse CLOCK is not required for circadian oscillator function.
Academic Article	CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock.
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	Antibodies for assessing circadian clock proteins in the rodent suprachiasmatic nucleus.
Academic Article	Putative melatonin receptors in a human biological clock.
Academic Article	Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses.
Concept	Suprachiasmatic Nucleus
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	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.

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Suprachiasmatic Nucleus