A5028218135- Circadian rhythm and melatonin
- Neurobiology and Insect Physiology Research
- Cancer, Hypoxia, and Metabolism
- Sleep and Wakefulness Research
- Metabolomics and Mass Spectrometry Studies
- Genetics, Aging, and Longevity in Model Organisms
- Birth, Development, and Health
- Cancer Research and Treatments
- Sulfur Compounds in Biology
- Mitochondrial Function and Pathology
- Cell Adhesion Molecules Research
- Eicosanoids and Hypertension Pharmacology
- Photoreceptor and optogenetics research
- Polyamine Metabolism and Applications
- Inflammatory mediators and NSAID effects
- Cancer, Stress, Anesthesia, and Immune Response
- Dietary Effects on Health
- High Altitude and Hypoxia
- Insect and Arachnid Ecology and Behavior
- Sarcoma Diagnosis and Treatment
- RNA regulation and disease
- Molecular Biology Techniques and Applications
- Analytical Chemistry and Chromatography
- Advanced Chemical Sensor Technologies
- Amino Acid Enzymes and Metabolism
University of Pennsylvania
2018-2024
Translational Therapeutics (United States)
2018-2024
California University of Pennsylvania
2021
Abstract Tumour cells frequently utilize glutamine to meet bioenergetic and biosynthetic demands of rapid cell growth. However, dependence can be highly variable between in vitro vivo settings, based on surrounding microenvironments complex adaptive responses deprivation. Soft tissue sarcomas (STSs) are mesenchymal tumours where cytotoxic chemotherapy remains the primary approach for metastatic or unresectable disease. Therefore, it is critical identify alternate therapies improve patient...
Abstract Circadian clocks coordinate mammalian behavior and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought drive these in most of cells. However, red blood cells (RBCs), which do not contain a nucleus, cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display regulation glucose metabolism, is required sustain daily oscillations. We found rhythms metabolite levels...
Chronic sleep loss profoundly impacts metabolic health and shortens lifespan, but studies of the mechanisms involved have focused largely on acute deprivation.
Circadian disruption influences metabolic health. Metabolism modulates circadian function. However, the mechanisms coupling rhythms and metabolism remain poorly understood. Here, we report that cystathionine β-synthase (CBS), a central enzyme in one-carbon metabolism, functionally interacts with core protein cryptochrome 1 (CRY1). In cells, CBS augments CRY1-mediated repression of CLOCK/BMAL1 complex shortens period. Notably, find mutant CBS-I278T protein, most common cause homocystinuria,...
Modern triple quadrupole mass spectrometers provide the ability to detect and quantify a large number of metabolites using tandem spectrometry (MS/MS). Liquid chromatography (LC) is advantageous, as it does not require derivatization procedures diversity in physiochemical characteristics analytes can be accommodated through variety column chemistries. Recently, comprehensive optimization LC-MS metabolomics design experiments (COLMeD) approach has been described used by our group develop...
Background: Large-scale, placebo-controlled trials established that nonsteroidal anti-inflammatory drugs confer a cardiovascular hazard: this has been attributed to depression of cardioprotective products cyclooxygenase (COX)–2, especially prostacyclin. An alternative mechanism by which might constrain cardioprotection is enhancing the formation methylarginines in kidney would limit action nitric oxide throughout vasculature. Methods: Targeted and untargeted metabolomics were used...
Sleep is regulated via circadian mechanisms, but effects of sleep disruption on physiological rhythms, in particular metabolic cycling, remain unclear. To examine this question, we probed diurnal alterations two Drosophila short mutants, fumin and sleepless. Samples were collected with high temporal sampling (every 2 h) over 24 h under a 12:12 light:dark cycle, profiling was done using an ion-switching LCMS/MS method. Fewer metabolites oscillations noted (50 46 sleepless, BH. Q < 0.2 by RAIN...
The brain is extensively vascularized, useŝ20% of the body's oxygen, and highly sensitive to changes in oxygen. While synaptic plasticity memory are impaired healthy individuals by exposure mild hypoxia, aged appear be even more sensitive. Aging associated with progressive failure pulmonary cardiovascular systems, exposing both chronic superimposed acute hypoxia. HIF proteins, "master regulators" cellular response robustly expressed neurons astrocytes. Astrocytes support via complex...
Abstract Circadian disruption influences metabolic health. Metabolism modulates circadian function. However, the mechanisms coupling rhythms and metabolism remain poorly understood. Here we report that Cystathionine β-synthase (CBS), a central enzyme in one-carbon metabolism, functionally interacts with core protein Cryptochrome1 (CRY1). In cells, CBS augments CRY1 mediated repression of CLOCK/BMAL1 complex shortens period. Notably, find mutant CBS-I278T protein, most common cause...
Abstract Chronic sleep loss profoundly impacts health in ways coupled to metabolism; however, much existing literature links and metabolism only on acute timescales. To explore the impact of chronically reduced sleep, we conducted unbiased metabolomics heads from three Drosophila short-sleeping mutants. Common features included elevated ornithine polyamines; lipid, acyl-carnitine, TCA cycle changes suggesting mitochondrial dysfunction. Biochemical studies overall, circulating, excreted...
Abstract Sleep is an almost universally required state in biology. Disrupted sleep has been associated with adverse health risks including metabolic perturbations. part regulated via circadian mechanisms, however, dysfunction at different times of day arising from disruption unclear. We used targeted liquid chromatography-mass spectrometry to probe alterations using high-resolution temporal sampling two Drosophila short mutants, fumin and sleepless , across a day. Discriminant analyses...
Abstract Rhythmicity is a cornerstone of behavioral and biological processes, especially metabolism, yet the mechanisms behind metabolite cycling remain elusive. This study uncovers robust oscillation in key pathways downstream glucose humans. A purpose-built 13 C 6 -glucose isotope tracing platform was used to sample Drosophila every 4h probe these pathways, revealing striking peak biosynthesis shortly after lights-on wild-type flies. hyperactive mutant ( fumin ) demonstrates increased...