A5005294294- Circadian rhythm and melatonin
- Adipose Tissue and Metabolism
- Genetics, Aging, and Longevity in Model Organisms
- Dietary Effects on Health
- Spaceflight effects on biology
- Peripheral Artery Disease Management
- Muscle Physiology and Disorders
- Mitochondrial Function and Pathology
- Light effects on plants
- Photoreceptor and optogenetics research
- Plant Molecular Biology Research
- Cardiovascular Effects of Exercise
- Pancreatic function and diabetes
- Sirtuins and Resveratrol in Medicine
- Chemotherapy-induced cardiotoxicity and mitigation
- Diabetic Foot Ulcer Assessment and Management
- Sleep and Wakefulness Research
- Cancer-related Molecular Pathways
- Cancer, Hypoxia, and Metabolism
- Coenzyme Q10 studies and effects
- Health, Environment, Cognitive Aging
- Genetics and Neurodevelopmental Disorders
- Endoplasmic Reticulum Stress and Disease
- Exercise and Physiological Responses
- PARP inhibition in cancer therapy
Northwestern University
2013-2025
University of Chicago
2019
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...
Ischemia-reperfusion (I/R) studies have implicated oxidant stress, the mitochondrial permeability transition pore (mPTP), and poly(ADP-ribose) polymerase (PARP) as contributing factors in myocardial cell death. However, interdependence of these intact, blood-perfused heart is not known. We therefore wanted to determine whether mPTP opening, PARP activity contribute same death pathway after I/R.A murine left anterior descending coronary artery (LAD) occlusion (30 minutes) release (1 4 hours)...
In mammals, circadian rhythms are entrained to the light cycle and drive daily oscillations in levels of NAD
The process of tissue regeneration occurs in a developmentally timed manner, yet the role circadian timing is not understood. Here, we identify for adult muscle stem cell (MuSC)-autonomous clock control following acute ischemic injury. We observed greater repair capacity injury during active/wake period as compared with inactive/rest mice, and loss Bmal1 within MuSCs leads to impaired regeneration. demonstrate that reduced activated MuSC number at day 3 postinjury, indicating failure...
Newborn mammalian cardiomyocytes quickly transition from a fetal to an adult phenotype that utilizes mitochondrial oxidative phosphorylation but loses mitotic capacity. We tested whether forced reversal of back glycolytic would restore proliferative deleted Uqcrfs1 (mitochondrial Rieske Iron-Sulfur protein, RISP) in hearts mice. As RISP protein decreased, heart function declined, and glucose utilization increased. Simultaneously, they underwent hyperplastic remodeling during which...
People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces stress is an essential cofactor for respiration. Oral nicotinamide riboside (NR) increases bioavailability of in humans. Among 90 people PAD, this randomized double-blind clinical trial assessed whether 6-months NR, without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At follow-up, NR...
Abstract The HMG-CoA reductase degradation protein 1 (HRD1) has been identified as a key enzyme for endoplasmic reticulum-associated of misfolded proteins, but its organ-specific physiological functions remain largely undefined. Here we show that mice with HRD1 deletion specifically in the liver display increased energy expenditure and are resistant to HFD-induced obesity steatosis insulin resistance. Proteomic analysis identifies interactome, large portion which includes metabolic...
In humans, chronic glucocorticoid use is associated with side effects like muscle wasting, obesity, and metabolic syndrome. Intermittent steroid dosing has been proposed in Duchenne Muscular Dystrophy patients to mitigate the seen daily intake. We evaluated biomarkers from patients, finding that, compared use, weekend was reduced serum insulin, free fatty acids, branched chain amino as well reduction fat mass despite having similar BMIs. reasoned that intermittent prednisone administration...
Exogenous glucocorticoids interact with the circadian clock, but little attention is paid to timing of intake. We recently found that intermittent once-weekly prednisone improved nutrient oxidation in dystrophic muscle. Here, we investigated whether dosage time affected effects on muscle bioenergetics. In mice treated prednisone, drug dosing light-phase promoted nicotinamide adenine dinucleotide (NAD + ) levels and mitochondrial function wild-type muscle, while this response was lost...
Abstract Following injury, skeletal muscle undergoes repair via satellite cell (SC)‐mediated myogenic progression. In SCs, the circadian molecular clock gene, Bmal1, is necessary for appropriate progression and with evidence that clocks can also affect force production. Utilizing a mouse model allowing inducible depletion of Bmal1 within we determined contractile function, SC damage following eccentric contractile‐induced injury. At baseline, SC‐ iKO animals exhibited ~20–25% reduction in...
Disruptions of circadian rhythms are widespread in modern society and lead to accelerated worsened symptoms metabolic syndrome. In healthy mice, the clock factor BMAL1 is required for skeletal muscle function metabolism. However, importance development diseases, such as diet-induced obesity (DIO), remains unclear. Here, we demonstrate that muscle–specific BMAL1-deficient mice exhibit glucose tolerance upon high-fat diet feeding, despite no evidence increased weight gain. Metabolite profiling...
Circadian rhythms orchestrate physiological processes such as metabolism, immune function, and tissue regeneration, aligning them with the optimal time of day (TOD). This study identifies an interplay between circadian clock within muscle stem cells (SCs) their capacity to modulate microenvironment during regeneration. We reveal that SC triggers TOD-dependent inflammatory gene transcription after injury, particularly genes related neutrophil activity chemotaxis. These responses are driven by...
Mitochondrial capacity is critical to adapt the high energy demand of heart circadian oscillations and diseased states. Glucocorticoids regulate cycle metabolism, but little known about how timing exogenous glucocorticoid dosing directly regulates metabolism through cardiomyocyte-autonomous mechanisms. While chronic once-daily intake glucocorticoids promotes metabolic stress failure, we recently discovered that intermittent once-weekly promoted muscle in normal obese skeletal muscle....