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Satchidananda Panda
Nationality	Indian-American
Alma mater	Orissa University of Agriculture and Technology, Scripps Research Institute
Scientific career
Fields	Chronobiology, Biology, Plant Biology, Neuroscience

Satchidananda Panda is a chronobiologist who is most well-known for his research in exploring the role of the melanopsin photoreceptor in circadian photoentrainment. With a joint appointment at the University of California San Diego and at the Salk Institute for Biological Studies, Panda is focusing his research on exploring the molecular mechanism of the mammalian circadian clock and the associated clinical and public health applications. Currently, through explorations of the circadian rhythmicity of metabolism in mice, Panda and his lab may have found one method to prevent obesity through the timing of eating.

Life

Panda spent his early life growing up in India. He graduated from Orissa University of Agriculture and Technology in Bhubaneswar, India with a Bachelor’s of Science degree in plant biology. He then went on to achieve a M.S. degree from Tamil Nadu Agricultural University in Tamil Nadu, India. After immigrating to the United States, he earned a Ph.D. at the Scripps Research Institute in La Jolla, California in the Kellogg School of Science and Technology in 2001, working in the lab of Steve Kay. In fulfillment of the requirements for his PhD, he completed a thesis entitled, “TEJ Defines a Role for Poly (ADP-Ribosyl)ation in Establishing Period Length of the Arabidopsis Circadian Oscillator.”

After earning his doctoral degree, Panda completed a postdoctoral fellowship at the Genomics Institute of the Novartis Research Foundation in San Diego in the lab of John Hogenesch, completing research focusing on rhythmic expression of circadian genes in mammals as well as circadian photoentrainment through the melanopsin photopigment. After completing his postdoctoral fellowship, Panda was appointed assistant professor at the University of California San Diego with a joint appointment at the Salk Institute for Biological Studies. At the Salk Institute, Panda serves as the Director of the Regulatory Biology Laboratory.

Panda’s current research is geared towards identifying both clinical and industrial applications of the molecular mechanism of the circadian clock, specifically as it relates to metabolism, cancer, sleep disorders and mood disorders. Panda has enjoyed a significant amount of press attention in recent years, cited in popular media publications ranging from the New York Times to Architect Magazine to Men’s Health. Panda has also been rewarded with several prestigious awards in the field including "Science Top Ten Breakthroughs of 2002" and a finalist for the Eppendorf Prize in Neuroscience.

Panda currently lives in San Diego with his wife and family. In his free time he enjoys photography.

Scientific Career

Circadian Photoentrainment in Mammals

One of the main focuses of Panda’s lab is circadian photoentrainment in mammals, specifically the role of melanopsin in circadian photoentrainment.

In 2002, Panda generated a line of melanopsin knockout (KO) mice using homologous recombination in mice embryonic stem cells by replacing the first exon of the melanopsin gene with a neomycin-resistant gene. Panda placed these mice in two different environments: a normal light-dark photoperiod using 480 nm light and constant darkness, and observed their subsequent behavior. Panda's results showed that these mice were still able to entrain to the light-dark photoperiod. However, melanopsin KO mice showed attenuated entrainment capabilities compared to wild type (WT) mice with a shift magnitude about half of the WT mice. Panda then exposed the melanopsin KO mice to the same wavelength as before but with varying intensities. He found that lower intensities produced the greatest entrainment differences between both mouse lines.

Melanopsin KO mice show decreased phase shift magnitudes following a 15-min pulse of 480 nm light compared to WT mice. The numbers above each bar indicate the number of mice used to generate the results.

In constant darkness, melanopsin KO mice free-ran properly, displaying no difference from WT mice. Panda then placed these mice in constant white light and observed a similar trend. Melanopsin KO mice displayed the expected circadian period lengthening, but not with the same magnitude as WT mice.

Melanopsin KO mice show attenuated shifts in circadian period following constant light exposure compared to WT mice. The numbers above each bar indicate the number of mice used to generate the results.

The results show that melanopsin does play a role in photoentrainment process, though it is not necessary. However, despite its role in photoentrainment, melanopsin does not seem directly involved in core circadian clock functions as the melanopsin KO mouse line did not display any observable changes in circadian activity rhythms.

In 2003, Panda crossed a melanopsin KO mouse line (Opn4^−/−) with a mouse line (rd/rd) lacking rods and cones in the retina. This generated a new mouse line which lacked both melanopsin and functional rods and cones. Using this line, Panda exposed mice to constant light and constant dark environments as well as normal light-dark photoperiods, similar to his 2002 experiment. Melanopsin KO mice lacking both rods and cones free ran in constant dark environments, mirroring the response of mice lacking only melanopsin. However, in constant light environments and normal light-dark photoperiods, mice lacking both melanopsin and functioning rods and cones free ran as well. There was no observable attempt to entrain the the light-dark cycle. When exposed to different light intensities and wavelengths, there was no change in the lack of entrainment. Thus, mice do not contain any other photoreceptor that is sufficient to induce photoentrainment. However, rods and cones or melanopsin alone is sufficient for photoentrainment.

Molecular Mechanism of Mammalian Circadian Rhythm

A large portion of Panda’s work as a chronobiologist has focused on using mouse models to create a better understanding of the molecular mechanism behind mammalian circadian rhythm. While there is well-documented evidence that biological processes such as metabolism and autophagy are under circadian control, Panda seeks to identify what mechanisms regulate these processes. Panda’s lab uses genetics and genomics to identify various genes under circadian control and then uses biochemical techniques to see how this circadian control is carried out. For example, when examining the transcription of the Clock and Bmal1 transcription factors within mouse liver, Panda discovered a histone lysine demethylase 1a (JARID1a) that enhances Clock-Bmal1 transcription. Without JARID1a, the period of the circadian rhythm is shortened and Per expression is lowered, thus showcasing its key role in proper circadian oscillation. Panda focused on developing a model for how JARID1a works to moderate the level of Per transcription by regulating the transition between its repression and activation

Much of Panda’s work about metabolism has centered on gluconeogenesis and glucose homeostasis, with profound implications for better understanding the importance of the timing of eating. For instance, Panda found that the circadian clock protein Cryptochrome regulates gluconeogenesis in the liver. Typical of his work, Panda focused on the mechanism through which this regulation occurs and discovered that a fasting signal activates the cAMP/CREB signaling that leads to gluconeogenesis, and Crytochrome inhibits this cAMP signaling and production. Therefore, the rhythmicity of Crytochrome shapes how the mammalian body responds to fasting at different times in the day. In addition, other clock proteins such as Bmal1 and Clock regulate glucose homeostasis. Without Bmal1 and Clock, the rhythmicity of glucose and triglyercerides is lost and gluconeogensis is respectively abolished or depressed. In fact, Bmal1 and Clock have been found to play a role in the recovery from insulin-induced hypoglycaemia.

Current Research

Much of Panda’s current research in the past 5 years or so focuses on the pathology of a disturbed circadian clock and novel functions for the circadian clock.

An influential study Panda’s lab undertook in 2012 concluded that significant disruption the mammalian circadian clock results in an inflammatory immune response. This experiment was performed by Knockout (KO) of the Cry circadian genes in mice set off a molecular signal transduction pathway making use of secondary messenger cAMP that resulted in highly elevated levels of cytokines that trigger inflammatory immune responses. A number of successive studies build upon this conclusion by suggesting that this inflammatory immune response could be implicated in a wide variety of pathologies ranging from cancer to mood disorders to chronic heart disease.

Similarly, another line of research Panda is currently exploring is attempting to identifying the genes responsible for the circadian character of the SCN. The gene Lhx1 was identified as a likely candidate for establishing the SCN as the circadian center of the mammalian organism. Panda his colleagues, Megumi Hatori and Shubhroz Gill, performed an experiment that attempted to identify genes that were highly expressed in the SCN and also showed phase-aligned responses to light. Using this procedure, the single gene that satisfied this criteria was discovered to be Lhx1. Later research in other labs confirmed this conclusion that the Lhx1 was the likely candidate for developing the circadian character of the SCN. As more information is gathered about the Lhx1 gene and its protein targets and function, numerous opportunities arise for drug development and practical applications, including perhaps the development of a pharmaceutical response to jet lag.

Selected Publications

• Melanopsin (Opn4) requirement for normal light-induced circadian phase shifting (2002)
• Coordinated transcription of key pathways in the mouse by the circadian clock (2002)
• Melanopsin Is Required for Non-Image-Forming Photic Responses in Blind Mice (2003)
• Illumination of the melanopsin signaling pathway (2005)
• Role of novel photopigment, melanopsin, in behavioral adaption to light (2007)
• CRY links the circadian clock and CREB-mediated gluconeogenesis (2010)
• Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the circadian clock (2011)

See Also

Circadian clock

Circadian rhythm

Obesity

Suprachiasmatic nucleus

External Links

Satchidananda Panda Lab Homepage