Paolo Sassone-Corsi

Paolo Sassone-Corsi
University of California, Irvine | UCI · Center for Epigenetics and Metabolism

Doctor of Philosophy

About

629
Publications
63,492
Reads
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58,011
Citations
Citations since 2016
99 Research Items
16993 Citations
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Introduction
Dr. Sassone-Corsi studies gene expression and signal transduction, with an emphasis on the links between cellular metabolism, epigenetics and the circadian clock. He received his PhD from the University of Naples. He was appointed Distinguished Professor of the Department of Pharmacology at UCI in 2006, serving from 2006 to 2011 as department chair. He later founded UCI Center for Epigenetics and Metabolism.
Additional affiliations
June 2017 - June 2020
INSERM U1223
Position
  • Managing Director
November 2011 - present
University of California, Irvine
Position
  • Professor (Full)
May 2006 - August 2010
University of California, Irvine
Position
  • Chair
Education
September 1974 - July 2020
University of Naples
Field of study
  • Biological Science

Publications

Publications (629)
Article
Life on Earth anticipates recurring 24-hour environmental cycles via genetically encoded molecular clocks active in all mammalian organs. Communication between these clocks controls circadian homeostasis. Intertissue communication is mediated, in part, by temporal coordination of metabolism. Here, we characterize the extent to which clocks in diffe...
Article
Full-text available
Objective: The circadian clock aligns physiology with the 24-hour rotation of Earth. Light and food are the main environmental cues (zeitgebers) regulating circadian rhythms in mammals. Yet, little is known about the interaction between specific dietary components and light in coordinating circadian homeostasis. Herein, we focused on the role of e...
Article
The gut microbiome influences cognition and behavior in mammals, yet its metabolic impact on the brain is only starting to be defined. Using metabolite profiling of antibiotics-treated mice, we reveal the microbiome as a key input controlling circadian metabolic cycles in the brain. Intra and inter-region analyses characterise the influence of the...
Chapter
Rhythmic locomotor activity is a commonly used readout of general circadian function in animals. For instance, measuring the activity of rodents in their home cages can provide information about circadian phase and period in response to genetic, pharmacological, and environmental manipulations. Herein, the use of infrared light sensors to measure c...
Chapter
Indirect calorimetry probes the relationship between fuel consumed and energy produced, and in doing so provides an estimation of whole-body energy expenditure and fuel preference. When assayed continuously in real-time, rhythms appear and illuminate the temporal regulation of energy metabolism by the circadian clock. Here we describe a method for...
Article
Full-text available
Food intake profoundly affects systemic physiology. A large body of evidence has indicated a link between food intake and circadian rhythms, and ~24-h cycles are deemed essential for adapting internal homeostasis to the external environment. Circadian rhythms are controlled by the biological clock, a molecular system remarkably conserved throughout...
Preprint
Full-text available
The circadian clock aligns physiology with the 24-hour rotation of Earth. Light and food are the main environmental cues (zeitgebers) regulating circadian rhythms in mammals. Yet, little is known about the interaction between specific dietary components and light in coordinating circadian homeostasis. Herein, we focused on essential amino acids and...
Article
Full-text available
Significance We analyzed the liver metabolome of mice deficient in the expression of the dopamine D2 receptor (D2R) in striatal medium spiny neurons (iMSN-D2RKO) and found profound changes in the liver circadian metabolome compared to control mice. Additionally, we show activation of dopaminergic circuits by acute cocaine administration in iMSN-D2R...
Preprint
Full-text available
Expressed throughout the body, the circadian clock system achieves daily metabolic homeostasis at every level of physiology, with clock disruption associated with metabolic disease (1, 2). Molecular clocks present in the brain, liver, adipose, pancreas and skeletal muscle each contribute to glucose homeostasis (3). However, it is unclear; 1) which...
Preprint
Full-text available
Life on Earth anticipates recurring 24-h environmental cycles via genetically-encoded molecular clocks active in all mammalian organs. Communication between these clocks is believed to control circadian homeostasis. Metabolism can be considered a form of inter-tissue communication language that results in temporal coordination of systemic metabolis...
Article
Full-text available
Tissue sensitivity and response to exercise vary according to the time of day and alignment of circadian clocks, but the optimal exercise time to elicit a desired metabolic outcome is not fully defined. To understand how tissues independently and collectively respond to timed exercise, we applied a systems biology approach. We mapped and compared g...
Article
Circadian rhythms provide temporal variation of a broad range of behavioral and physiological functions, which is precisely controlled by the internal molecular gear, the circadian clock. However, circadian clock functions decline concomitantly with aging-dependent functional deterioration, such as metabolic dysfunction. Metabolic deterioration is...
Article
Full-text available
A growing number of epidemiological and experimental studies has established that circadian disruption is strongly associated with psychiatric disorders, including major depressive disorder (MDD). This association is becoming increasingly relevant considering that modern lifestyles, social zeitgebers (time cues) and genetic variants contribute to d...
Chapter
The circadian clock governs multiple biological functions at the molecular level and plays an essential role in providing temporal diversity of behavior and physiology including neuronal activity. Studies spanning the past two decades have deciphered the molecular mechanisms of the circadian clock, which appears to operate as an essential interface...
Article
The mammalian circadian clock, expressed throughout the brain and body, controls daily metabolic homeostasis. Clock function in peripheral tissues is required, but not sufficient, for this task. Because of the lack of specialized animal models, it is unclear how tissue clocks interact with extrinsic signals to drive molecular oscillations. Here, we...
Article
Full-text available
Ketone bodies are bioactive metabolites that function as energy substrates, signaling molecules, and regulators of histone modifications. β-hydroxybutyrate (β-OHB) is utilized in lysine β-hydroxybutyrylation (Kbhb) of histones, and associates with starvation-responsive genes, effectively coupling ketogenic metabolism with gene expression. The emerg...
Article
Full-text available
The circadian clock driven by the daily light–dark and temperature cycles of the environment regulates fundamental physiological processes and perturbations of these sophisticated mechanisms may result in pathological conditions, including cancer. While experimental evidence is building up to unravel the link between circadian rhythms and tumorigen...
Article
Regulating multiple body clocks Circadian rhythms that affect multiple tissues and organ systems are aligned with the dark-light cycle and other external inputs such as feeding. But how is such time keeping modulated throughout complex systems and anatomical regions? Koronowski and Sassone-Corsi reviewed how central regulators in the brain and peri...
Article
All neuronal cells hold the same genetic information but vary by their structural and functional plasticity depending on the brain area and environmental influences. Such variability involves specific gene regulation, which is driven by transcription factors (TFs). In the field of neuroscience, epigenetics is the main mechanism that has been invest...
Preprint
Ketone bodies are evolutionarily conserved metabolites that function as energy substrates, signaling molecules and epigenetic regulators. β-hydroxybutyrate (β-OHB) is utilized in lysine β-hydroxybutyrylation (Kbhb) of histones, which associates with starvation-responsive genes, effectively coupling ketogenic metabolism with gene expression. The eme...
Article
Full-text available
Circadian gene expression driven by transcription activators CLOCK and BMAL1 is intimately associated with dynamic chromatin remodeling. However, how cellular metabolism directs circadian chromatin remodeling is virtually unexplored. We report that the S-adenosylhomocysteine (SAH) hydrolyzing enzyme adenosylhomo-cysteinase (AHCY) cyclically associa...
Article
Significance Nutrition and the body clock are deeply intertwined, both impinging on our physiological health. Food composition can dramatically rewire peripheral clock metabolism; however, whether food challenges can impact circadian metabolism of the master clock in the suprachiasmatic nucleus (SCN) or other brain areas has not been fully explored...
Article
Full-text available
The proliferation in the rate of diagnosis of obesity and type 2 diabetes mellitus continues unabated, with current recommendations for primary lifestyle changes (i.e. modification to dietary patterns) having a limited impact in reducing the incidence of these metabolic diseases. Part of the reason for the failure to alter nutritional practices is...
Article
Full-text available
Gene and protein expressions display circadian oscillations, which can be disrupted in diseases in most body organs. Whether these oscillations occur in the healthy hippocampus and whether they are altered in epilepsy are not known. We identified more than 1200 daily oscillating transcripts in the hippocampus of control mice and 1600 in experimenta...
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
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Time-restricted feeding (TRF) improves metabolism independent of dietary macronutrient composition or energy restriction. To elucidate mechanisms underpinning the effects of short-term TRF, we investigated skeletal muscle and serum metabolic and transcriptomic profiles from 11 men with overweight/obesity after TRF (8 h day-1) and extended feeding (...
Article
Full-text available
Substance abuse disorders are linked to alteration of circadian rhythms, although the molecular and neuronal pathways implicated have not been fully elucidated. Addictive drugs, such as cocaine, induce a rapid increase of dopamine levels in the brain. Here, we show that acute administration of cocaine triggers reprogramming in circadian gene expres...
Article
Circadian rhythms govern a large array of physiological and metabolic functions. Perturbations of the daily cycle have been linked to elevated risk of developing cancer as well as poor prognosis in patients with cancer. Also, expression of core clock genes or proteins is remarkably attenuated particularly in tumours of a higher stage or that are mo...
Article
Full-text available
Metabolic syndrome has increased at a worrisome level. Lifestyle changes are not sufficient to prevent and improve the adverse effects of obesity, thus novel interventions are necessary. The aim of this study was to investigate the use and metabolic outcomes of a non-pharmacological intervention in a high-fat diet (HFD) fed mouse model, capable of...
Article
Full-text available
Circadian rhythms govern physiology and metabolism, leading to controlled homeostasis. We discuss the impact of circadian rhythms on society and the challenges for the imminent future of personalized medicine. © 2020 Greco and Sassone-Corsi. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites lice...
Article
Full-text available
The transcription factor BMAL1 is a core element of the circadian clock that contributes to cyclic control of genes transcribed by RNA polymerase II. By using biochemical cellular fractionation and immunofluorescence analyses we reveal a previously uncharacterized nucleolar localization for BMAL1. We used an unbiased approach to determine the BMAL1...
Article
Full-text available
Life evolved in the presence of alternating periods of light and dark that accompany the daily rotation of the Earth on its axis. This offered an advantage for organisms able to regulate their physiology to anticipate these daily cycles. In each light-sensitive organism studied, spanning single-celled bacteria to complex mammals, there exist timeke...
Article
Accumulating evidence points to a significant link between disrupted circadian rhythms and neuronal disfunctions, though the molecular mechanisms underlying this connection are virtually unexplored. The transcript Homer1a, an immediate early gene related to postsynaptic signaling, has been demonstrated to exhibit robust circadian oscillation in the...
Article
Full-text available
Circadian rhythms disruption can be the cause of chronic diseases. External cues, including therapeutic drugs, have been shown to modulate peripheral-circadian clocks. Since anthracycline cardiotoxicity is associated with loss of mitochondrial function and metabolic remodeling, we investigated whether the energetic failure induced by sub-chronic do...
Article
Full-text available
Have you ever asked yourself why you have energy during the day and feel tired at night? What if I told you that there is a part of your body that is secretly controlling these feelings without you knowing? Well there is! It is called your biological clock or circadian rhythm, and it is ticking away inside you right now. What is really amazing is t...
Article
Binge drinking and chronic exposure to ethanol contribute to alcoholic liver diseases (ALDs). A potential link between ALDs and circadian disruption has been observed, though how different patterns of alcohol consumption differentially impact hepatic circadian metabolism remains virtually unexplored. Using acute versus chronic ethanol feeding, we r...
Article
Mammals rely on a network of circadian clocks to control daily systemic metabolism and physiology. The central pacemaker in the suprachiasmatic nucleus (SCN) is considered hierarchically dominant over peripheral clocks, whose degree of independence, or tissue-level autonomy, has never been ascertained in vivo. Using arrhythmic Bmal1-null mice, we g...
Article
Full-text available
Autophagy and energy metabolism are known to follow a circadian pattern. However, it is unclear whether autophagy and the circadian clock are coordinated by common control mechanisms. Here, we show that the oscillation of autophagy genes is dependent on the nutrient-sensitive activation of TFEB and TFE3, key regulators of autophagy, lysosomal bioge...
Article
Full-text available
Loss of synchrony between geophysical time and insulin action predisposes to metabolic diseases. Yet the brain and peripheral pathways linking proper insulin effect to diurnal changes in light-dark and feeding-fasting inputs are poorly understood. Here, we show that the insulin sensitivity of several metabolically relevant tissues fluctuates during...
Article
Circadian rhythms control organismal physiology throughout the day. At the cellular level, clock regulation is established by a self-sustained Bmal1-dependent transcriptional oscillator network. However, it is still unclear how different tissues achieve a synchronized rhythmic physiology. That is, do they respond independently to environmental sign...
Article
While the timing of food intake is important, it is unclear whether the effects of exercise on energy metabolism are restricted to unique time windows. As circadian regulation is key to controlling metabolism, understanding the impact of exercise performed at different times of the day is relevant for physiology and homeostasis. Using high-throughp...
Article
The function of histone proteins can be modified through addition or removal of certain chemical groups. The addition of a serotonin molecule is a newly found histone modification that could influence gene expression.
Article
The circadian clock is an endogenous, time-tracking system that directs multiple metabolic and physiological functions required for homeostasis. The master or central clock located within the suprachiasmatic nucleus in the hypothalamus governs peripheral clocks present in all systemic tissues, contributing to their alignment and ultimately to tempo...
Article
The circadian clock is a complex cellular mechanism that, through the control of diverse metabolic and gene expression pathways, governs a large array of cyclic physiological processes. Epidemiological and clinical data reveal a connection between the disruption of circadian rhythms and cancer that is supported by recent preclinical data. In additi...
Article
Full-text available
The circadian clock operates as intrinsic time-keeping machinery to preserve homeostasis in response to the changing environment. While food is a known zeitgeber for clocks in peripheral tissues, it remains unclear how lack of food influences clock function. We demonstrate that the transcriptional response to fasting operates through molecular mech...
Article
Full-text available
The circadian clock allows physiological systems to adapt to their changing environment by synchronizing their timings in response to external stimuli. Previously, we reported clock-controlled adaptive responses to heat-shock and oxidative stress and showed how the circadian clock interacts with BMAL1 and HSF1. Here, we present a similar clock-cont...
Article
Metabolic diseases are often characterized by circadian misalignment in different tissues, yet how altered coordination and communication among tissue clocks relate to specific pathogenic mechanisms remains largely unknown. Applying an integrated systems biology approach, we performed 24-hr metabolomics profiling of eight mouse tissues simultaneous...
Article
Full-text available
Aging is accompanied by impairments in both circadian rhythmicity and long-term memory. Although it is clear that memory performance is affected by circadian cycling, it is unknown whether age-related disruption of the circadian clock causes impaired hippocampal memory. Here, we show that the repressive histone deacetylase HDAC3 restricts long-term...
Data
List of significant gradient serum metabolites under HFD.
Data
List of significant gradient muscle metabolites under HCD.
Data
List of significantly changed serum metabolites in the morning by nutritional challenges.
Data
List of significant gradient muscle metabolites under HFD.
Data
Figure S1: Experimental overview of human morning-evening metabolomics study. (A and B) Overview of the experimental design. (A) Each participant (n = 8) completed the experimental conditions in a random order. Human subjects consumed HFD and HCD in a randomized, crossover study with a 7-day washout between each dietary challenge. (B) Serum and mus...
Data
List of significant gradient serum metabolites under HCD.
Data
List of significantly changed serum metabolites in the evening by nutritional challenges.
Data
List of significantly changed muscle metabolites in the morning by nutritional challenges.