Research

Satchin Panda, an associate professor in the Regulatory Biology Laboratory, is interested in understanding the molecular mechanism of the biological clock in a mouse model system. The biological clock or circadian oscillator in most organisms coordinates behavior and physiology with the natural light-dark cycle. His laboratory uses genetic, genomics and biochemical approaches to identify genes under circadian regulation in different organs and to understand the mechanism of such regulation. His lab also tries to characterize the mechanism by which the circadian oscillator is synchronized to the natural light-dark condition. Both classical rod/cone photoreceptors and a newly identified ocular photopigment melanopsin participate in photoentrainment of the clock. Research in his lab is geared towards identifying molecular components and events critical for transmitting light information from the eye to the master oscillator in the brain.

"Going to bed at night and waking up in the morning is a seemingly simple routine we follow in every season. I want to understand how our brain clock keeps track of time in all seasons and time zones and tells our body when to sleep, when to wake up, and when to eat."

In mammals, the circadian timing system is composed of a central circadian clock in the brain and subsidiary oscillators in most peripheral tissues. The master clock in the brain is set by light and determines the overall diurnal or nocturnal preference of an animal, including sleep-wake cycles and feeding behavior. The clocks in peripheral organs, however, are largely insensitive to changes in the light regime. Instead, their phase and amplitude are affected by many factors, including feeding time.

All clocks keep time through the fall and rise of gene activity on a roughly 24-hour schedule that anticipates environmental changes and adapts many of the body's physiological functions to the appropriate time of day. In particular, the oscillator in the liver–the body's metabolic clearinghouse–helps the organism adapt to a daily pattern of food availability by temporally tuning the activity of thousands of genes regulating metabolism and physiology.

To investigate whether the circadian rhythms in hepatic transcription were solely controlled by the liver's clock in anticipation of food or responded to actual food intake, Panda and his team put normal mice and mice without functional clocks on strictly controlled feeding and fasting schedules. Their experiments revealed that the daily waxing and waning of thousands of genes in the liver is mostly controlled by food intake and not, as conventional wisdom had it, by the body's circadian clock. For example, the activity of genes that encode enzymes needed to break down sugars rose immediately after a meal, while the activity of genes encoding enzymes needed to break down fat was highest after a prolonged fast. Consequently, a clearly defined daily feeding schedule puts the enzymes of metabolism in shift work and optimizes burning of sugar and fat.

Their findings could explain why shift workers are unusually prone to metabolic syndrome, diabetes, high cholesterol levels, and obesity. It is not the shift work per se that wreaks havoc on the body's metabolism but changing shifts and weekends, when workers switch back to a regular day-night cycle.

Left to right:
Ruth Fischer, Hiep Le, Chrissta Maracle, Satchin Panda, Luciano DiTacchio, Christopher Vollmers, Megumi Hirota, Sheena Keding

Selected Publications

Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong E, Gill S, Leblanc M, Chaix A, Joens M, Fitzpatrick J, Ellisman M, Panda S. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metabolism (in press)

Cho H, Zhao X, Hatori M, Yu RT, Barish GD, Lam MT, Chong LW, DiTacchio L, Atkins AR, Glass CK, Liddle C, Auwerx J, Downes M, Panda S, Evans RM. Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β. Nature. 2012 Mar 29;485(7396):123-7. [pdf]

Siegert S, Cabuy E, Scherf BG, Kohler H, Panda S, Le YZ, Fehling HJ, Gaidatzis D, Stadler MB, Roska B. Transcriptional code and disease map for adult retinal cell types. Nat Neurosci. 2012 Jan 22;15(3):487-95, S1-2. [pdf]

DiTacchio L, Le HD, Vollmers C, Hatori M, Witcher M, Secombe J, Panda S. Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the circadian clock. Science. 2011 Sep 30;333(6051):1881-5. [pdf]

Ma D, Panda S, Lin JD. Temporal orchestration of circadian autophagy rhythm by C/EBPβ. EMBO J. 2011 Sep 6;30(22):4642-51. [pdf]

Gill S, Panda S. Feeding Mistiming Decreases Reproductive Fitness in Flies. Cell Metab. 2011 Jun 8;13(6):613-4. [pdf]

Brown TM, Gias C, Hatori M, Keding SR, Semo M, Coffey PJ, Gigg J, Piggins HD, Panda S, Lucas RJ. Melanopsin contributions to irradiance coding in the thalamo-cortical visual system. PLoS Biol. 2010 Dec 7;8(12):e1000558. [pdf]

Hatori M, Panda S. CRY links the circadian clock and CREB-mediated gluconeogenesis. Cell Res. 2010 Dec;20(12):1285-8. Epub 2010 Nov 9. [pdf]

Jones MA, Covington MF, DiTacchio L, Vollmers C, Panda S, Harmer SL. Jumonji domain protein JMJD5 functions in both the plant and human circadian systems. Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21623-8. Epub 2010 Nov 29. [pdf]

Hatori M, Panda S. The emerging roles of melanopsin in behavioral adaptation to light. Trends Mol Med. 2010 Oct;16(10):435-46. Epub 2010 Aug 31. [pdf]

Vollmers C, Gill S, DiTacchio L, Pulivarthy SR, Le HD, Panda S. Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression. Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21453-8. Epub 2009 Nov 25. [pdf]

Lamia KA, Sachdeva UM, DiTacchio L, Williams EC, Alvarez JG, Egan DF, Vasquez DS, Juguilon H, Panda S, Shaw RJ, Thompson CB, Evans RM. AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science. 2009 Oct 16;326(5951):437-40

Hitomi K, DiTacchio L, Arvai AS, Yamamoto J, Kim ST, Todo T, Tainer JA, Iwai S, Panda S, Getzoff ED. Functional motifs in the (6-4) photolyase crystal structure make a comparative framework for DNA repair photolyases and clock cryptochromes. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):6962-7. Epub 2009 Apr 9

Hughes ME, DiTacchio L, Hayes KR, Vollmers C, Pulivarthy S, Baggs JE, Panda S, Hogenesch JB. Harmonics of circadian gene transcription in mammals. PLoS Genet. 2009 Apr;5(4):e1000442. Epub 2009 Apr 3

Baggs JE, Price TS, DiTacchio L, Panda S, Fitzgerald GA, Hogenesch JB. Network features of the mammalian circadian clock. PLoS Biol. 2009 Mar 10;7(3):e52.

Vollmers C, Panda S, DiTacchio L. A high-throughput assay for siRNA-based circadian screens in human U2OS cells. PLoS One. 2008;3(10):e3457. Epub 2008 Oct 20 [pdf]

Lin B, Koizumi A, Tanaka N, Panda S, Masland RH. Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin. Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):16009-14. Epub 2008 Oct 3

Hatori M, Le H, Vollmers C, Keding SR, Tanaka N, Schmedt C, Jegla T, Panda S. Inducible ablation of melanopsin-expressing retinal ganglion cells reveals their central role in non-image forming visual responses. PLoS ONE. 2008 Jun 11;3 (6):e2451.[pdf]

Pulivarthy SR, Tanaka N, Welsh DK, DeHaro L, Verm IM, Panda S. Reciprocity between phase shifts and amplitude changes in the mammalian circadian clock. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20356-61. Epub 2007 Dec 7. [pdf]

Kozlov SV, Bogenpohl JW, Howell MP, Wevrick R, Panda S, Hogenesch JB, Muglia LJ, Van Gelder RN, Herzog ED, Stewart CL. The imprinted gene Magel2 regulates normal circadian output. Nat Genet. 2007 Oct;39(10):1266-72. Epub 2007 Sep 23. [pdf]

Miller BH, McDearmon EL, Panda S, Hayes KR, Zhang J, Andrews JL, Antoch MP, Walker JR, Esser KA, Hogenesch JB, Takahashi JS. Circadian and CLOCK-controlled regulation of the mouse transcriptome and cell proliferation. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3342-7. Epub 2007 Feb 20. [pdf]

Panda S. Multiple photopigments entrain the Mammalian circadian oscillator. Neuron. 2007 Mar 1;53(5):619-21. Review. [pdf]

Nayak SK, Jegla T, Panda S. Role of novel photopigment, melanopsin, in behavioral adaption to light. Cell Mol Life Sci. 2007 Jan; 64(2):144-54. [pdf]

De Haro L, Panda S. Systems biology of circadian rhythms: an outlook. J Biol Rhythms. 2006 Dec; 21(6): 507-18.

Rudic RD, McNamara P, Reilly D, Grosser T, Curtis AM, Price TS, Panda S, Hogenesch JB, FitzGerald GA. Bioinformatic analysis of circadian gene oscillation in mouse aorta. Circulation. 2005 Oct 25;112(17):2716-24. Epub 2005 Oct 17.[pdf]

Panda S, Nayak SK, Campo B, Walker JR, Hogenesch JB, Jegla T. Illumination of the melanopsin signaling pathway. Science. 2005. Jan 28;307(5709):600-4. [pdf]

Rudic RD, McNamara P, Curtis AM, Boston RC, Panda S, Hogenesch JB, Fitzgerald GA. BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biol. 2004 Nov;2(11):e377. [pdf]

Panda S, Hogenesch JB. It's all in the timing: many clocks, many outputs. J Biol Rhythms. 2004 Oct;19(5):374-87.

Sato TK, Panda S, Miraglia LJ, Reyes TM, Rudic RD, McNamara P, Naik KA,FitzGerald GA, Kay SA, Hogenesch JB. A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Neuron. 2004 Aug 19;43(4):527-37. [pdf]

Grechez-Cassiau A, Panda S, Lacoche S, Teboul M, Azmi S, Laudet V, Hogenesch JB, Taneja R, Delaunay F. The transcriptional repressor STRA13 regulates a subset of peripheral circadian outputs. J Biol Chem 2004 Jan 9; 279(2):1141-50. [pdf]

Panda S, Provencio I, Tu DC, Pires SS, Rollag MD, Castrucci AM, Pletcher MT, Sato TK, Wiltshire T, Andahazy M, Kay SA, Van Gelder RN, Hogenesch JB. Melanopsin is required for non-image-forming photic responses in blind mice. Science. 2003 Jul 25;301(5632):525-7. [pdf]

Sato TK, Panda S, Kay SA, Hogenesch JB. DNA arrays: applications and implications for circadian biology. J Biol Rhythms. 2003 Apr;18(2):96-105

Panda S, Sato TK, Hampton GM, Hogenesch JB. An array of insights: application of DNA chip technology in the study of cell biology. Trends Cell Biol. 2003 Mar;13(3):151-6. [pdf]

Panda S, Sato TK, Castrucci AM, Rollag MD, DeGrip WJ, Hogenesch JB, Provencio I, Kay SA. Melanopsin (Opn4) requirement for normal light-induced circadian phase shifting. Science. 2002 Dec 13;298(5601):2213-6. [pdf]

Ceriani MF, Hogenesch JB, Yanovsky M, Panda S, Straume M, Kay SA. Genome-wide expression analysis in Drosophila reveals genes controlling circadian behavior. J Neurosci. 2002 Nov 1;22(21):9305-19. [pdf]

Panda S, Poirier GG, Kay SA. tej defines a role for poly(ADP-ribosyl)ation in establishing period length of the arabidopsis circadian oscillator. Dev Cell. 2002 Jul;3(1):51-61.

Panda S, Hogenesch JB, Kay SA. Circadian rhythms from flies to human. Nature. 2002 May 16;417(6886):329-35. [pdf]

Panda S, Antoch MP, Miller BH, Su AI, Schook AB, Straume M, Schultz PG, Kay SA, Takahashi JS, Hogenesch JB. Coordinated transcription of key pathways in the mouse by the circadian clock. Cell. 2002 May 3;109(3):307-20. [pdf]

Harmer SL, Panda S, Kay SA. Molecular bases of circadian rhythms. Annu Rev Cell Dev Biol. 2001;17:215-53. [pdf]

Salk News Releases

• Salk scientists redraw the blueprint of the body's biological clock
  April 5, 2012
• "Alarm clock" gene explains wake-up function of biological clock
  September 29, 2011
• Salk Institute promotes latest generation of extraordinary scientists
  April 15, 2011
• Melanopsin looks on the bright side of life
  December 7, 2010
• Feeding the clock
  November 24, 2009
• Perfect vision but blind to light
  June 11, 2008
• Salk Institute researcher named Pew Scholar
  June 29, 2006
• Human Biological Clock Sensor Uses Fly Eye 'Technology'
  January 27, 2005

Links

Panda lab

Health & Your Internal Clock