A5010151045- Cancer, Hypoxia, and Metabolism
- Metabolomics and Mass Spectrometry Studies
- Advanced MRI Techniques and Applications
- Advanced Chemical Physics Studies
- Catalysis and Oxidation Reactions
- Catalytic Processes in Materials Science
- Diet and metabolism studies
- CAR-T cell therapy research
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Atmospheric chemistry and aerosols
- Advanced NMR Techniques and Applications
- Medical Imaging Techniques and Applications
- Immune Cell Function and Interaction
- Industrial Gas Emission Control
- ATP Synthase and ATPases Research
- Lanthanide and Transition Metal Complexes
- Epilepsy research and treatment
- Metabolism and Genetic Disorders
- Metabolism, Diabetes, and Cancer
- Spectroscopy and Laser Applications
- Amino Acid Enzymes and Metabolism
- Chemical Reactions and Isotopes
- Cancer Research and Treatments
- Atmospheric Ozone and Climate
California University of Pennsylvania
2021-2025
University of Pennsylvania
2015-2024
Philadelphia University
2021
University of Minnesota
2006-2015
Cornell University
2013-2015
Resonance Research (United States)
2006-2015
University of Minnesota Medical Center
2010-2012
University Radiology
2009
Twin Cities Orthopedics
2008
Catholic University of America
2003-2005
Aerobic glycolysis or the Warburg Effect (WE) is characterized by increased metabolism of glucose to lactate. It remains unknown what quantitative changes activity are necessary and sufficient for this phenotype. We developed a computational model an integrated analysis using metabolic control (MCA), metabolomics data, statistical simulations. identified confirmed novel mode regulation specific aerobic where flux through GAPDH, enzyme separating lower upper glycolysis, rate-limiting step in...
The antitumor agent lonidamine (LND; 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid) is known to interfere with energy-yielding processes in cancer cells. However, the effect of LND on central energy metabolism has never been fully characterized. In this study, we report that a significant amount succinate accumulated LND-treated inhibits formation fumarate and malate suppresses succinate-induced respiration isolated mitochondria. Utilizing biochemical assays, determined...
Cancer cells adapt their metabolism during tumorigenesis. We studied two isogenic breast cancer lines (highly metastatic 4T1; nonmetastatic 67NR) to identify differences in glucose and glutamine response metabolic environmental stress. Dynamic magnetic resonance spectroscopy of 13C-isotopomers showed that 4T1 have higher glycolytic tricarboxylic acid (TCA) cycle flux than 67NR readily switch between glycolysis oxidative phosphorylation (OXPHOS) different extracellular environments. OXPHOS...
The serine, glycine, one-carbon (SGOC) metabolic network is implicated in cancer pathogenesis, but its general functions are unknown. We carried out a computational reconstruction of the SGOC and then characterized expression across thousands tissues. Pathways including methylation redox metabolism exhibited heterogeneous indicating strong context dependency their usage tumors. From an analysis coexpression, simultaneous up- or downregulation nucleotide synthesis, NADPH, glutathione...
Abstract Acetate, a glial‐specific substrate, is an attractive alternative to glucose for the study of neuronal‐glial interactions. The present investigates kinetics acetate uptake and utilization in rat brain vivo during infusion [2‐ 13 C]acetate using NMR spectroscopy. When plasma concentration was increased, rate (CMR ace ) increased progressively reached close saturation > 2–3 mM, whereas continued increase. Michaelis–Menten constant ( = 0.01 ± 0.14 mM) much smaller than transport...
Approximately half of all cancer patients present with cachexia, a condition in which disease-associated metabolic changes lead to severe loss skeletal muscle mass. Working toward an integrated and mechanistic view we investigated the hypothesis that promotes mitochondrial uncoupling muscle. We subjected mice vivo phosphorous-31 nuclear magnetic resonance (31P NMR) spectroscopy murine samples gas chromatography/mass spectrometry (GC/MS). The used both experiments were Lewis lung carcinoma...
Lymphodepletion (LD) is an integral component of chimeric antigen receptor T-cell (CART) immunotherapies. In this study, we compared the safety and efficacy bendamustine (Benda) to standard fludarabine/cyclophosphamide (Flu/Cy) LD before CD19-directed, CD28-costimulated CART axicabtagene ciloleucel (axi-cel) for patients with large B-cell lymphoma (LBCL) follicular (FL). We analyzed 59 diagnosed LBCL (n = 48) FL 11) consecutively treated axi-cel at University Pennsylvania. also serum samples...
Glucose is the primary fuel for brain function, and determining kinetics of cerebral glucose transport utilization critical quantifying energy metabolism. The kinetic parameters transport, K(M)(t) V(max)(t), in humans have so far been obtained by measuring steady-state levels proton ((1)H) NMR as a function plasma fitting models to these data. Extraction necessitated assuming constant metabolic rate (CMR(glc)) from other tracer studies, such (13)C NMR. Here we present new methodology...
Cell surface molecules transiently upregulated on activated T cells can play a counter-regulatory role by inhibiting cell function. Deletion or blockade of such immune checkpoint receptors has been investigated to improve the function engineered effector cells. CD38 is cells, and although there have studies showing that an inhibitory in how it does so not fully elucidated. In comparison with as PD1, CTLA4, LAG3, TIM3, we found displays more sustained intense expression following acute...
We present the results of a randomized, open-label pilot study investigating combination oral vancomycin and stereotactic body radiotherapy (SBRT) in early-stage non-small cell lung cancer (NSCLC). Our findings highlight vancomycin's safety, evidenced by absence Grade 3 or 4 adverse events, its potential to enhance antitumor efficacy SBRT. The observed enhancement is linked modulation gut microbiota, which triggers significant metabolic changes immune activation, thereby contributing...
Abstract Metabolic modeling of 13 C NMR spectroscopy ( MRS) data using two‐compartment neuronal‐glial models enabled non‐invasive measurements the glutamate‐glutamine cycle rate (V NT ) in brain vivo. However, reliability such metabolic has not been examined thoroughly. This study uses Monte‐Carlo simulations to investigate positional enrichment time courses measured amino acids as glutamate and glutamine during [1‐ C]‐ or [1,6‐ 2 ]glucose infusion. Results show that determination V is very...
To investigate the effect of acute insulin-induced hypoglycemia on cerebral glucose metabolism in healthy humans, measured by (13)C magnetic resonance spectroscopy (MRS).Hyperinsulinemic clamps were performed at plasma levels 5 mmol/L (euglycemia) or 3 (hypoglycemia) random order eight subjects (four women) two occasions, separated least weeks. Enriched [1-(13)C]glucose 20% w/w was used for to maintain stable labeling. The (13)C-labeled metabolites glutamate C4 and C3 over time occipital...
We present the first validated metabolic network model for analysis of flux through key pathways tumor intermediary metabolism, including glycolysis, oxidative and non-oxidative arms pentose pyrophosphate shunt, TCA cycle as well its anaplerotic pathways, pyruvate-malate shuttling, glutaminolysis, fatty acid biosynthesis oxidation. The that is called Bonded Cumomer Analysis application to (13)C magnetic resonance spectroscopy ((13)C MRS) data Fragmented mass spectrometric a refined efficient...
Two variants of a widely used two-compartment model were prepared for fitting the time course [1,6- 13 C 2 ]glucose metabolism in rat brain. Features common to most models included, but one enrichment substrates entering glia and neuronal citric acid cycles was allowed differ. Furthermore, included capacity analyze multiplets arising from spin-spin coupling, known improve parameter estimates heart. Data analyzed literature report providing courses metabolism. Four analyses used, two...