A5063607134- Circadian rhythm and melatonin
- Pancreatic function and diabetes
- Photoreceptor and optogenetics research
- Genetics, Aging, and Longevity in Model Organisms
- Plant Molecular Biology Research
- Light effects on plants
- Sirtuins and Resveratrol in Medicine
- Retinal Development and Disorders
- Dietary Effects on Health
- Neurobiology and Insect Physiology Research
- Lipid metabolism and biosynthesis
- Adipose Tissue and Metabolism
- Spaceflight effects on biology
- Diet, Metabolism, and Disease
- Diabetes and associated disorders
- Psychological and Temporal Perspectives Research
- Immune Cell Function and Interaction
- Sleep and Wakefulness Research
- Neuroendocrine regulation and behavior
- Adenosine and Purinergic Signaling
- Neuroscience and Neuropharmacology Research
Northwestern University
2005-2024
Genomics (United Kingdom)
2010
Circadian clocks are self-sustained cellular oscillators that synchronize oxidative and reductive cycles in anticipation of the solar cycle. We found clock transcription feedback loop produces nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, adenosine triphosphate production, mitochondrial respiration through modulation protein acetylation to metabolic pathways with 24-hour fasting feeding control activity NAD(+)-dependent deacetylase sirtuin 3 (SIRT3) generated rhythms enzymes...
The mammalian transcription factors CLOCK and BMAL1 are essential components of the molecular clock that coordinate behavior metabolism with solar cycle. Genetic or environmental perturbation circadian cycles contributes to metabolic disorders including type 2 diabetes. To study impact cell-autonomous on pancreatic β cell function, we examined islets from mice either intact disrupted expression both throughout life limited adulthood. We found pronounced oscillation insulin secretion was...
Interactions between lineage-determining and activity-dependent transcription factors determine single-cell identity function within multicellular tissues through incompletely known mechanisms. By assembling a atlas of chromatin state human islets, we identified β cell subtypes governed by either high or low activity the factor pancreatic duodenal homeobox-1 (PDX1). cells with reduced PDX1 displayed increased accessibility at latent nuclear κB (NF-κB) enhancers. Pdx1 hypomorphic mice...
The mammalian circadian clock is encoded by an autoregulatory transcription feedback loop that drives rhythmic behavior and gene expression in the brain peripheral tissues. Transcriptomic analyses indicate cell type-specific effects of cycles on physiology, although how respond to environmental stimuli remains incompletely understood. Here, we show activation inducible factor NF-κB response inflammatory leads marked inhibition repressors, including Period, Cryptochrome, Rev-erb genes, within...
Genetic and molecular approaches have been critical for elucidating the mechanism of mammalian circadian clock. Here, we demonstrate that ClockΔ19 mutant behavioral phenotype is significantly modified by mouse strain genetic background. We map a suppressor mutation to ∼900 kb interval on chromosome 1 identify transcription factor, Usf1, as responsible gene. A SNP in promoter Usf1 causes elevation its transcript protein strains suppress Clock phenotype. USF1 competes with CLOCK:BMAL1 complex...
In mammals, circadian rhythms are entrained to the light cycle and drive daily oscillations in levels of NAD
We performed genome-wide chemical mutagenesis of C57BL/6J mice using N -ethyl- -nitrosourea (ENU). Electroretinographic screening the third generation offspring revealed two G3 individuals from one G1 family with a normal a-wave but lacking b-wave that we named nob4 . The mutation was transmitted recessive mode inheritance and mapped to chromosome 11 in region containing Grm6 gene, which encodes metabotropic glutamate receptor protein, mGluR6. Sequencing confirmed single nucleotide...
Most laboratory mouse strains including C57BL/6J do not produce detectable levels of pineal melatonin owing to deficits in enzymatic activity arylalkylamine N -acetyltransferase (AANAT) and -acetylserotonin O -methyl transferase (ASMT), two enzymes necessary for biosynthesis. Here we report that alleles segregating at these loci C3H/HeJ mice, an inbred strain producing melatonin, suppress the circadian period-lengthening effect Clock mutation. Through a functional mapping approach, localize...
The circadian clock is encoded by a negative transcriptional feedback loop that coordinates physiology and behavior through molecular programs remain incompletely understood. Here, we reveal rhythmic genome-wide alternative splicing (AS) of pre-mRNAs encoding regulators peptidergic secretion within pancreatic β cells are perturbed in
The mammalian circadian clock drives daily oscillations in physiology and behavior through an autoregulatory transcription feedback loop present central peripheral cells. Ablation of the core within endocrine pancreas adult animals impairs splicing genes involved hormone exocytosis causes hypoinsulinemic diabetes. Here, we developed a genetically sensitized small-molecule screen to identify druggable proteins mechanistic pathways β-cell failure. Our approach was generate β-cells expressing...
We performed genome-wide mutagenesis of C57BL/6J mice using the mutagen N -ethyl- -nitrosourea (ENU) and screened third generation (G3) offspring for visual system alterations electroretinography fundus photography. Several in one pedigree showed characteristics retinal degeneration when tested at 12–14 weeks age: no recordable electroretinogram (ERG), attenuation vessels, speckled pigmentation fundus. Histological studies that retinas undergo a photoreceptor with apoptotic loss outer...
Summary The mammalian circadian clock drives daily oscillations in physiology and behavior through an autoregulatory transcription feedback loop present central peripheral cells. Ablation of the core within endocrine pancreas adult animals impairs splicing genes involved hormone exocytosis causes hypoinsulinemic diabetes. However, identification druggable proteins pathways to ameliorate burden metabolic disease remains a challenge. Here, we generated β cells expressing nano-luciferase...