A5064711982- Circadian rhythm and melatonin
- Light effects on plants
- Genetics, Aging, and Longevity in Model Organisms
- Photoreceptor and optogenetics research
- Dietary Effects on Health
- Spaceflight effects on biology
- Sleep and Wakefulness Research
- Sleep and related disorders
- Plant Molecular Biology Research
- Gene Regulatory Network Analysis
- Epigenetics and DNA Methylation
- Neuroscience of respiration and sleep
- Diet and metabolism studies
- CRISPR and Genetic Engineering
- Plant and Biological Electrophysiology Studies
- Adipose Tissue and Metabolism
- Genomics and Rare Diseases
- Photosynthetic Processes and Mechanisms
- Health, Environment, Cognitive Aging
- Lymphoma Diagnosis and Treatment
- Alkaloids: synthesis and pharmacology
- Antioxidants, Aging, Portulaca oleracea
- Long-Term Effects of COVID-19
- Nephrotoxicity and Medicinal Plants
- Biofield Effects and Biophysics
University of Florida
2018-2025
Florida College
2018-2025
University of California, San Diego
2008-2022
University of Memphis
2009-2018
Center for Genomic Science
2017
Genomics Institute of the Novartis Research Foundation
2007-2010
Scripps Research Institute
2004-2007
Cleveland Clinic
1986
University of Pittsburgh
1983
The mammalian circadian clockwork is composed of a core PER/CRY feedback loop and additional interlocking loops. In particular, the ROR/REV/Bmal1 loop, consisting ROR activators REV-ERB repressors that regulate Bmal1 expression, thought to "stabilize" clock function. However, due functional redundancy pleiotropic effects gene deletions, role has not been accurately defined. this study, we examined cell-autonomous oscillations using combined knockout RNA interference demonstrated REV-ERBalpha...
The circadian clock controls daily oscillations of gene expression at the cellular level. We report development a high-throughput functional assay system that consists luminescent reporter cells, screening automation, and data analysis pipeline. applied this to further dissect molecular mechanisms underlying mammalian using chemical biology approach. analyzed effect 1,280 pharmacologically active compounds with diverse structures on period length is indicative core mechanism. Our paradigm...
Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout day. These methods hold significant promise for future discovery, when combined with computational modeling. However, genome-scale experiments are costly laborious, yielding “big data” that conceptually statistically difficult analyze. There is no obvious consensus...
The circadian clock coordinates physiology and metabolism. mTOR (mammalian/mechanistic target of rapamycin) is a major intracellular sensor that integrates nutrient energy status to regulate protein synthesis, metabolism, cell growth. Previous studies have identified key role for in regulating photic entrainment synchrony the central suprachiasmatic nucleus (SCN). Given activities exhibit robust oscillations variety tissues cells including SCN, here we continued investigate orchestrating...
Cellular circadian clocks direct a daily transcriptional program that supports homeostasis and resilience. Emerging evidence has demonstrated age-associated changes in functions. To define age-dependent at the systems level, we profile transcriptome hypothalamus, lung, heart, kidney, skeletal muscle, adrenal gland three age groups. We find tissue-specific clock output changes. Aging reduces number of rhythmically expressed genes (REGs), indicative weakened control. REGs are enriched for...
Abstract The basic helix–loop–helix (bHLH) family of transcription factors recognizes DNA motifs known as E-boxes (CANNTG) and includes 108 members 1 . Here we investigate how chromatinized are engaged by two structurally diverse bHLH proteins: the proto-oncogene MYC-MAX circadian factor CLOCK-BMAL1 (refs. 2,3 ). Both bind to preferentially near nucleosomal entry–exit sites. Structural studies with engineered or native nucleosome sequences show that triggers release from histones gain...
Bmal1 is an essential transcriptional activator within the mammalian circadian clock. We report here that suprachiasmatic nucleus (SCN) of Bmal1-null mutant mice, unexpectedly, generates stochastic oscillations with periods overlap range. Dissociated SCN neurons expressed fluctuating levels PER2 detected by bioluminescence imaging but could not generate intrinsically. Inhibition intercellular communication or cyclic-AMP signaling in slices, which provide a positive feed-forward signal to...
Circadian timekeeping by intracellular molecular clocks is evident widely in prokaryotes and eukaryotes. The clockworks are driven autoregulatory feedback loops that lead to oscillating levels of components whose maxima fixed phase relationships with one another. These the key metric characterizing operation clocks. In this study, we built a mathematical model from regulatory structure circadian clock mice identified its parameters using an iterative evolutionary strategy, minimum cost...
Over the last decades, researchers have characterized a set of "clock genes" that drive daily rhythms in physiology and behavior. This arduous work has yielded results with far-reaching consequences metabolic, psychiatric, neoplastic disorders. Recent attempts to expand our understanding circadian regulation moved beyond mutagenesis screens identified first clock components, employing higher throughput genomic proteomic techniques. In order further accelerate gene discovery, we utilized...
In animals, circadian rhythms in physiology and behavior result from coherent rhythmic interactions between clocks the brain those throughout body. Despite many tissue specific clocks, most understanding of molecular core clock mechanism comes studies suprachiasmatic nuclei (SCN) hypothalamus a few other cell types. Here we report establishment genetic characterization three cell-autonomous mouse models: 3T3 fibroblasts, 3T3-L1 adipocytes, MMH-D3 hepatocytes. Each model is genetically...
Diurnal oscillation of intracellular redox potential is known to couple metabolism with the circadian clock, yet responsible mechanisms are not well understood. We show here that chemical activation NRF2 modifies gene expression and rhythmicity, phenotypes similar genetic activation. Loss Nrf2 function in mouse fibroblasts, hepatocytes liver also altered rhythms, suggesting stoichiometry and/or timing important timekeeping some cells. Consistent this concept, at a time corresponding peak...
The circadian clock orchestrates diverse physiological processes critical for health and disease. CREB, hepatocyte specific (CREBH) is a liver-enriched, endoplasmic reticulum (ER)–tethered transcription factor known to regulate the hepatic acute phase response energy homeostasis under stress conditions. We demonstrate that CREBH regulated by functions as regulator of lipid metabolism. Proteolytic activation in liver exhibits typical rhythmicity controlled core oscillator BMAL1 AKT/glycogen...
In mammals, the circadian clock coordinates cell physiological processes including inflammation. Recent studies suggested a crosstalk between these two pathways. However, mechanism of how inflammation affects is not well understood. Here, we investigated role proinflammatory transcription factor NF-κB in regulating function. Using combination genetic and pharmacological approaches, show that perturbation canonical subunit RELA human U2OS cellular model altered core gene expression. While...