Dr. Green is a Professor and Distinguished Scholar of Neuroscience at the University of Texas Southwestern Medical Center in Dallas, Texas. Her lab studies the molecular mechanism of the mammalian circadian clock and how it controls rhythmic physiology. She originally identified the rhythmic gene Nocturnin and demonstrated that this gene encodes an NADP(H) phosphatase, an enzyme that converts NADP(H) to NAD(H). Her studies of Nocturnin function have led to the discovery that this protein is a key circadian regulator of lipid metabolism and oxidative stress responses. Her lab continues to focus on Nocturnin and its role in metabolism, as well as studying more broadly the general role of the circadian clock in metabolism and aging. The Green lab also works on the molecular mechanism of the central clock and on circadian gene expression patterns through post-transcriptional regulation of mRNA stability and translation.
Before moving to UT Southwestern, Dr. Green was a Professor of Biology at the University of Virginia. She has received multiple awards, participated in several NIH and NSF study sections and advisory committees, chaired numerous scientific meetings, and is a member of the Editorial Board for Journal of Biological Rhythmsand former Associate Editor of Neurobiology of Sleep and Circadian Rhythms. She was also served as President of Society for Research on Biological Rhythms from 2016-2018. Dr. Green received her Ph.D. and completed a postdoctoral fellowship in the Department of Biochemistry and Molecular Biology and the Department of Anatomy and Cell Biology, respectively, at the University of Kansas Medical Center.
In her free time, Dr. Green loves to hike and ski in the Colorado mountains and play the piano.
The general focus of the Green Lab is to understand the molecular mechanism of the mammalian circadian clock, how it controls rhythmic biochemistry, physiology and behavior and how loss of clock function can impact health, resulting in metabolic disease, cancer and other ailments. My lab studies these questions using techniques ranging from atomic level protein structures, biochemistry and cell biological techniques to whole animal physiology and behavior.
Our studies fall into two major areas of focus:
(1) The molecular mechanism of the core circadian clock.
The circadian clock is an endogenous intracellular timekeeping machine that has a period length of about 24 hours. This clock is not dependent on external cycles of light and dark, but these and other environmental inputs can reset the clock so that it is synchronized to local time. Although it is known that the clock mechanism is a transcription/translation negative feedback loop, many aspects of the mechanism are still not understood. We use cellular, biochemical and molecular approaches to dissect the roles of the various clock components to understand how the clock keeps time, how it maintains the appropriate period length and how clocks throughout the body are reset and synchronized.
(2) The mechanisms by which the clock drives rhythmic physiology with a focus on metabolism and aging.
The core circadian clock drives rhythmic expression of thousands of genes that vary with tissue type. These genes encode proteins that generate rhythms in metabolism, hormone secretion, body temperature, immune response and many other physiological phenomena. These rhythms decline with disease and during aging. The Green Lab studies how the circadian clock controls metabolism, oxidative stress responses and aging. One of the focuses of our lab is on the rhythmic protein Nocturnin that is an NADP(H) phosphatase. Loss of this protein in mice prevents diet-induced obesity and protects against oxidative stress and our goal is to understand how rhythms in NADP(H) levels cause these phenotypes.
Importance of circadian timing for aging and longevity.Acosta-Rodríguez VA, Rijo-Ferreira F, Green CB, Takahashi JS, Nat Commun 2021 05 12 1 2862
Spatiotemporal regulation of NADP(H) phosphatase Nocturnin and its role in oxidative stress response.Laothamatas I, Gao P, Wickramaratne A, Quintanilla CG, Dino A, Khan CA, Liou J, Green CB, Proc Natl Acad Sci U S A 2020 01 117 2 993-999
Periodicity, repression, and the molecular architecture of the mammalian circadian clock.Rosensweig C, Green CB Eur. J. Neurosci. 2018 Nov
An evolutionary hotspot defines functional differences between CRYPTOCHROMES.Rosensweig C, Reynolds KA, Gao P, Laothamatas I, Shan Y, Ranganathan R, Takahashi JS, Green CB Nat Commun 2018 Mar 9 1 1138
Temporal Control of Metabolic Amplitude by Nocturnin.Stubblefield JJ, Gao P, Kilaru G, Mukadam B, Terrien J, Green CB Cell Rep 2018 Jan 22 5 1225-1235
Mice under Caloric Restriction Self-Impose a Temporal Restriction of Food Intake as Revealed by an Automated Feeder System.Acosta-Rodríguez VA, de Groot MHM, Rijo-Ferreira F, Green CB, Takahashi JS Cell Metab. 2017 Jul 26 1 267-277.e2
Molecular assembly of the period-cryptochrome circadian transcriptional repressor complex.Nangle SN, Rosensweig C, Koike N, Tei H, Takahashi JS, Green CB, Zheng N Elife 2014 Aug e03674
Phosphorylation of the Cryptochrome 1 C-terminal tail regulates circadian period length.Gao P, Yoo SH, Lee KJ, Rosensweig C, Takahashi JS, Chen BP, Green CB J. Biol. Chem. 2013 Oct
Kiss your tail goodbye: The role of PARN, Nocturnin, and Angel deadenylases in mRNA biology.Godwin AR, Kojima S, Green CB, Wilusz J Biochim. Biophys. Acta 2012 Dec
Circadian control of mRNA polyadenylation dynamics regulates rhythmic protein expression.Kojima S, Sher-Chen EL, Green CB Genes Dev. 2012 Dec 26 24 2724-36
Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex.Huang N, Chelliah Y, Shan Y, Taylor CA, Yoo SH, Partch C, Green CB, Zhang H, Takahashi JS Science2012 Jul 337 6091 189-94
Central and peripheral circadian clocks in mammals.Mohawk JA, Green CB, Takahashi JS Annu. Rev. Neurosci. 2012 35 445-62
Nocturnin regulates circadian trafficking of dietary lipid in intestinal enterocytes.Douris N, Kojima S, Pan X, Lerch-Gaggl AF, Duong SQ, Hussain MM, Green CB Curr. Biol. 2011 Aug 21 16 1347-55
McCarthy, E.V., Baggs, J.E., Geskes, J.M., Hogenesch, J.B. and Green, C.B. (2009) Generation of a novel allelic series of cryptochrome mutants via mutagenesis reveals residues involved in protein:protein interaction and CRY2-specific repression. Mol. Cell Biol. 29: 5465-5476.
Green, C.B., Takahashi, J.S. and Bass, J. (2008) The meter of metabolism. Cell 134: 2-16.
Green, C.B.*, Douris, N.*, Kojima, S., Strayer, C.A., Fogerty, J., Lourim, D., Keller, S. and Besharse, J.C. (2007) Loss of nocturnin, a circadian deadenylase, confers resistance to hepatic steatosis and diet-induced obesity. Proc. Natl. Acad. Sci., U.S.A., 104: 9888-9893.
van der Schalie, E.A., Conte, F.E., Marz, K.E. and Green, C.B. (2007) Structure/function analysis of Xenopus CRYPTOCHROME 1 and 2 reveals differential nuclear localization mechanisms and functional domains important for interaction with and repression of CLOCK:BMAL1. Mol. Cell Biol. 27: 2120-2129.
Garbarino-Pico, E., Rollag, M.D., Strayer, C.A., Niu, S., Besharse, J.C., and Green, C.B. (2007) Immediate early response of the circadian polyA ribonuclease nocturnin to two extracellular stimuli. RNA 13: 745-755.
Zhu, H., Conte, F. and Green, C.B. (2003) Nuclear localization and transcriptional repression are confined to separable domains in the circadian protein CRYPTOCHROME. Curr. Biol., 13: 1653-1658.
Kojima, S., Matsumoto, K., Hirose, M., Shimada, M., Nagano, M., Shigeyoshi, Y., Hoshino, S., Green, C.B., Sakaki, Y., and Tei, H. (2007) LARK activates post-transcriptional expression of an essential mammalian clock protein, PERIOD1. Proc. Natl. Acad. Sci, U.S.A. 104: 1859-1864.
Baggs, J. and Green, C.B. (2003) Nocturnin, a deadenylase in Xenopus laevis retina: a mechanism for posttranscriptional control of circadian-related mRNA. Curr. Biol. 13: 189-198.