Cellular Circadian Clocks
In mammals, a hierarchical system of circadian clock cells in the brain and throughout the body orchestrates daily patterns of physiology and behavior. These daily patterns persist under constant conditions as "circadian rhythms". Our lab studies circadian rhythms in single cells using bioluminescence imaging to monitor clock gene expression, multielectrode arrays to monitor neuronal firing, and fluorescence imaging to monitor cytoplasmic calcium. We are interested in the autonomy, heterogeneity, and coupling of cellular circadian clocks, particularly the "master" clock cells of the brain, the neurons of the suprachiasmatic nucleus. We are also interested in how defects in these mechanisms may contribute to circadian rhythm disorders in humans, especially mood disorders.
Welsh DK, Takahashi JS, Kay SA. Suprachiasmatic nucleus: cell autonomy and network properties. Annu Rev Physiol 72:551-77, 2010.
Leise TL, Wang CW, Gitis PJ, Welsh DK. Persistent cell-autonomous circadian oscillations in fibroblasts revealed by six-week single-cell imaging of PER2::LUC bioluminescence. PLoS One 7:e33334, 2012.
Welsh DK, Noguchi T. Cellular bioluminescence imaging. Cold Spring Harb Protoc DOI: 10.1101/pdb.top070607, 2012.
McCarthy MJ, Welsh DK. Cellular circadian clocks in mood disorders. J Biol Rhythms 27:339-52, 2012.
Noguchi T, Wang LL, Welsh DK. Fibroblast PER2 circadian rhythmicity depends on cell density. J Biol Rhythms 28:183-92, 2013.
McCarthy MJ, Wei H, Marnoy Z, Darvish R, McPhie D, Cohen B, Welsh DK. Genetic and clinical factors predict lithium’s effects on PER2 gene expression rhythms in cells from bipolar disorder patients. Transl Psychiatry 3:e318, 2013.
Landgraf D, Long J, Der-Avakian A, Streets M, Welsh DK. Dissociation of learned helplessness and fear conditioning in mice: a mouse model of depression. PLoS One 10(4):e0125892, 2015.