A5043157066- Circadian rhythm and melatonin
- Light effects on plants
- Dietary Effects on Health
- Plant Molecular Biology Research
- Diet and metabolism studies
- Gene Regulatory Network Analysis
- Photoreceptor and optogenetics research
- Genetics, Aging, and Longevity in Model Organisms
- Adipose Tissue and Metabolism
- Epigenetics and DNA Methylation
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Spaceflight effects on biology
- Endoplasmic Reticulum Stress and Disease
- Viral Infectious Diseases and Gene Expression in Insects
- Lipid metabolism and biosynthesis
- Sperm and Testicular Function
- Cholesterol and Lipid Metabolism
- Sexual Differentiation and Disorders
- Protein Tyrosine Phosphatases
- Autophagy in Disease and Therapy
- Galectins and Cancer Biology
- Ubiquitin and proteasome pathways
- Metabolomics and Mass Spectrometry Studies
- Genetics and Neurodevelopmental Disorders
University of Kansas Medical Center
2014-2024
Salk Institute for Biological Studies
2008-2012
Circadian clocks coordinate behavioral and physiological processes with daily light-dark cycles by driving rhythmic transcription of thousands genes. Whereas the master clock in brain is set light, pacemakers peripheral organs, such as liver, are reset food availability, although setting, or "entrainment," mechanisms remain mysterious. Studying mouse fibroblasts, we demonstrated that nutrient-responsive adenosine monophosphate-activated protein kinase (AMPK) phosphorylates destabilizes...
In mammals, the circadian oscillator generates approximately 24-h rhythms in feeding behavior, even under constant environmental conditions. Livers of mice held darkness exhibit rhythm abundance up to 15% expressed transcripts. Therefore, oscillations hepatic transcripts could be driven by rhythmic food intake or sustained oscillator, a combination both. To address this question, we used distinct and fasting paradigms on wild-type (WT) clock-deficient mice. We monitored temporal patterns...
The circadian clock is a molecular and cellular oscillator found in most mammalian tissues that regulates rhythmic physiology behavior. Numerous investigations have addressed the contribution of rhythmicity to cellular, organ, organismal physiology. We recently developed method look at transcriptional oscillations with unprecedented precision accuracy using high-density time sampling. Here, we report comparison oscillating transcription from mouse liver, NIH3T3, U2OS cells. Several...
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...
In animals, circadian oscillators are based on a transcription-translation circuit that revolves around the transcription factors CLOCK and BMAL1. We found JumonjiC (JmjC) ARID domain-containing histone lysine demethylase 1a (JARID1a) formed complex with CLOCK-BMAL1, which was recruited to Per2 promoter. JARID1a increased acetylation by inhibiting deacetylase 1 function enhanced CLOCK-BMAL1 in demethylase-independent manner. Depletion of mammalian cells reduced Per promoter acetylation,...
The mammalian circadian clock is a cell-autonomous system that drives oscillations in behavior and physiology anticipation of daily environmental change. To assess the robustness human molecular clock, we systematically depleted known components observed are maintained over wide range disruptions. We developed novel strategy termed Gene Dosage Network Analysis (GDNA) which small interfering RNA (siRNA)-induced dose-dependent changes gene expression were used to build association networks...
Circadian clocks are near-ubiquitous molecular oscillators that coordinate biochemical, physiological, and behavioral processes with environmental cues, such as dawn dusk. timing mechanisms thought to have arisen multiple times throughout the evolution of eukaryotes but share a similar overall structure consisting interlocking transcriptional posttranslational feedback loops. Recent work in both plants animals has also linked modification histones circadian clock function. Now, using data...
Homologous flavoproteins from the photolyase (PHR)/cryptochrome (CRY) family use FAD cofactor in PHRs to catalyze DNA repair and CRYs tune circadian clock control development. To help address how PHR/CRY members achieve these diverse functions, we determined crystallographic structure of Arabidopsis thaliana (6-4) PHR (UVR3), which is strikingly (>65%) similar sequence human CRYs. The reveals a substrate-binding cavity specific for UV-induced lesion, photoproduct, binding sites different...
Alcoholic liver disease encompasses a wide spectrum of pathogenesis including steatosis, fibrosis, cirrhosis, and alcoholic steatohepatitis. Autophagy is lysosomal degradation process that degrades cellular proteins damaged/excess organelles, serves as protective mechanism in response to various stresses. Acute alcohol treatment induces autophagy via FoxO3a-mediated gene expression protects against alcohol-induced steatosis injury mice. Farnesoid X Receptor (FXR) nuclear receptor regulates...
The advent of siRNA-based screens has revolutionized the efficiency by which functional components biological processes are identified. A notable exception been field mammalian circadian rhythms. Here, we outline a medium- to high-throughput approach that, in combination with real-time bioluminescence measurement reporter gene, can be utilized elucidate effects gene knockdown across several days human cells.
The circadian oscillator is a molecular feedback circuit whose orchestration involves posttranslational control of the activity and protein levels its components. Although controlled proteolysis proteins critical for function, our understanding underlying mechanisms remains incomplete. Here, we report that JmjC domain-containing 5 (JMJD5) interacts with CRYPTOCHROME 1 (CRY1) in an F-box/leucine-rich repeat 3 (FBXL3)-dependent manner facilitates targeting CRY1 to proteasome. Genetic deletion...
A growing body of evidence supports the potential role circadian system and chromatin remodeling genes in autism. Considering heterogeneity gender discrepancy autism, complex nature epigenetic landscape, identification biologically relevant factors requires reducing using proper subtyping. For this study, we used X chromosome inactivation (XCI) status females with autism as an marker for subtyping examined expression level members KDM5, a gene family. KDM5 are histone demethylases involved...
The mammalian circadian clock is an autoregulatory feedback process that responsible for homeostasis in mouse livers. These processes are well understood at the gene-level, however, not isoform-level. To investigate oscillations isoform-level, we used nanopore-based R2C2 method to create over 78 million highly-accurate, full-length cDNA reads 12 RNA samples extracted from livers collected 2 hour intervals. generate a liver isoform-level transcriptome, processed these using Mandalorion tool...
The liver is a key regulator of systemic energy homeostasis whose proper function dependent on the circadian clock. Here, we show that livers deficient in oscillator component JARID1a exhibit dysregulation genes involved metabolism. Importantly, find mice lack hepatic have decreased lean body mass, respiratory exchange ratios, faster production ketones, and increased glucose response to fasting. Finally, loss compromises transcriptome nutrient availability. In all, ablation disrupts...
The advent of siRNA-based screens has revolutionized the efficiency by which functional components biological processes are identified.A notable exception been field mammalian circadian rhythms.Here, we outline a medium-to high-throughput approach that, in combination with real-time bioluminescence measurement reporter gene, can be utilized to elucidate effects gene knockdown across several days human cells.
Abstract The liver is a key regulator of systemic energy homeostasis whose proper function dependent on the circadian clock. Here, we show that livers deficient in oscillator component JARID1a exhibit dysregulation genes involved metabolism. Importantly, find mice lack hepatic have decreased lean body mass, respiratory exchange ratios, faster production ketones and increased glucose response to fasting. Finally, loss compromises transcriptome nutrient availability. In all, ablation disrupts...
The liver is a key regulator of systemic energy homeostasis whose proper function dependent on the circadian clock. Here, we show that livers deficient in oscillator component JARID1a exhibit dysregulation genes involved metabolism. Importantly, find mice lack hepatic have decreased lean body mass, respiratory exchange ratios, faster production ketones and increased glucose response to fasting. Finally, loss compromises transcriptome nutrient availability. In all, ablation disrupts...