|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 Medical School||2001-2006|
|Director, Graduate Program in Neuroscience, UMass Medical School||2005-|
|Professor, UMass 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. We continue to generate line of mice with targeted disruption of genes relevant to circadian rhythms. Other areas of interest are to identify the effects of clock gene mutations on other behavioral and physiological processes, including sleep, 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.