A5089946986- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- Epigenetics and DNA Methylation
- Metabolomics and Mass Spectrometry Studies
- Amino Acid Enzymes and Metabolism
- Glioma Diagnosis and Treatment
- Genetic Syndromes and Imprinting
- Metabolism and Genetic Disorders
- Hedgehog Signaling Pathway Studies
- RNA Research and Splicing
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Autophagy in Disease and Therapy
- Liver Disease Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- Organ Transplantation Techniques and Outcomes
- Advanced NMR Techniques and Applications
- Atomic and Subatomic Physics Research
- NMR spectroscopy and applications
- Marine Bivalve and Aquaculture Studies
- PI3K/AKT/mTOR signaling in cancer
- Microtubule and mitosis dynamics
- Advanced MRI Techniques and Applications
- Multiple Myeloma Research and Treatments
- Neuroscience and Neuropharmacology Research
University of North Carolina at Chapel Hill
2015-2025
Children's Center
2023
Center for Neurosciences
2023
Emory University
2023
Children's Healthcare of Atlanta
2023
University of North Carolina Health Care
2022
North Carolina State University
2010-2017
UNC/NCSU Joint Department of Biomedical Engineering
2013-2017
Indiana University School of Medicine
2016
North Central State College
2010-2014
OLIG2-expressing tumor stem cells have been shown to drive recurrence in Sonic Hedgehog (SHH)-subgroup medulloblastoma (MB) and patients urgently need specific therapies target this cell population. Here, we investigate the therapeutic potential of brain-penetrant orally bioavailable, OLIG2 inhibitor CT-179, using SHH-MB explant organoids, PDX GEM models. We find that CT-179 disrupts dimerization, phosphorylation DNA binding alters cell-cycle kinetics, increasing differentiation apoptosis....
The tumor suppressor p53 has recently been shown to regulate energy metabolism through multiple mechanisms. However, the in vivo signaling pathways related p53-mediated metabolic regulation remain largely uncharacterized. By using mice bearing a single amino acid substitution at cysteine residue 305 of mouse double minute 2 (Mdm2(C305F)), which renders Mdm2 deficient binding ribosomal proteins (RPs) RPL11 and RPL5, we show that RP-Mdm2-p53 pathway is critical for sensing nutrient deprivation...
Graft failure after liver transplantation may involve mitochondrial dysfunction. We examined whether prevention of injury would improve graft function. Orthotopic rat was performed 18 hours' cold storage in University Wisconsin solution and treatment with vehicle, minocycline, tetracycline, or N -methyl-4-isoleucine cyclosporin (NIM811) explants recipients. Serum alanine aminotransferase (ALT), necrosis, apoptosis were assessed 6 hours implantation. Mitochondrial polarization cell viability...
While aerobic glycolysis is linked to unconstrained proliferation in cancer, less known about its physiological role. Why this metabolic program that promotes tumor growth preserved the genome has thus been unresolved. We tested hypothesis derives from developmental processes regulate rapid proliferation.
Abstract Activation of p53 in response to DNA damage is essential for tumor suppression. Although previous studies have emphasized the importance p53-dependent cell cycle arrest and apoptosis suppression, recent suggested that other areas regulation, such as metabolism repair (DDR), are also However, intrinsic connections between p53-mediated DDR metabolic regulation remain incompletely understood. Here, we present data suggesting promotes nucleotide biosynthesis by repressing expression...
The Eastern oyster (Crassostrea virginica) is a useful, robust model marine organism for tissue metabolism studies. Its relatively few organs are easily delineated and there sufficient understanding of their functions based on classical assays to support interpretation advanced spectroscopic approaches. Here we apply high-resolution proton nuclear magnetic resonance ((1)H NMR)-based metabolomic analysis C. virginica investigate the differences in metabolic profile different organ groups,...
Aerobic glycolysis supports proliferation through unresolved mechanisms. We have previously shown that aerobic is required for the regulated of cerebellar granule neuron progenitors (CGNP) and growth CGNP-derived medulloblastoma. Blocking initiation via deletion hexokinase-2 (Hk2) disrupts CGNP restricts medulloblastoma growth. Here, we assessed whether disrupting pyruvate kinase-M (Pkm), an enzyme acts in terminal steps glycolysis, would alter metabolism, proliferation, tumorigenesis....
We report a nanoparticle formulation of the SHH-pathway inhibitor vismodegib that improves efficacy for medulloblastoma, while reducing toxicity. Limited blood–brain barrier (BBB) penetration and dose-limiting extitle/citraneural toxicities complicate systemic therapies brain tumors. Vismodegib is FDA-approved SHH-driven basal cell carcinoma, but implementation medulloblastoma has been limited by inadequate excessive bone To address these issues through optimized drug delivery, we formulated...
Heterotrimeric G-protein-mediated signaling pathways play a pivotal role in transmembrane eukaryotes. Our main aim was to identify regulated by A. nidulans GprB and GprD G-protein coupled receptors (GPCRs). When these two null mutant strains were compared the wild-type strain, ΔgprB showed an increased protein kinase A (PKA) activity while growing glucose 1% during starvation. In contrast, ΔgprD has much lower PKA upon Transcriptomics (1)H NMR-based metabolomics performed on single mutants...
Environmental and endogenous electrophiles cause tissue damage through their high reactivity with nucleophiles such as DNA, proteins, lipids. Protection against is mediated by glutathione (GSH) conjugation, which can occur spontaneously or be facilitated the S-transferase (GST) enzymes. To determine role of GST enzymes in protection well specific families mediating this protection, we exposed mutant mouse lines lacking GSTP, GSTM, and/or GSTT enzyme to model electrophile acrylamide, a...
Recurrence is the primary life-threatening complication for medulloblastoma (MB). In Sonic Hedgehog (SHH)-subgroup MB, OLIG2-expressing tumor stem cells drive recurrence. We investigated anti-tumor potential of small-molecule OLIG2 inhibitor CT-179, using SHH-MB patient-derived organoids, xenograft (PDX) tumors and mice genetically-engineered to develop SHH-MB. CT-179 disrupted dimerization, DNA binding phosphorylation altered cell cycle kinetics
The metabolism of 2-13C/15N-glycine and U-13C-glucose was determined in four tissue blocks (adductor muscle, stomach digestive gland, mantle, gills) the Eastern oyster (Crassostrea virginica) using proton (1H) carbon-13 (13C) nuclear magnetic resonance (NMR) spectroscopy. oysters were treated aerated seawater with three treatments (5.5 mM U-13C-glucose, 2.7 2-13C/15N-glycine, 5.5 plus 2-13C/15N-glycine) relative mass balance 13C fractional enrichments blocks. In all tissues, glycine...
Abstract Pancreatic ductal adenocarcinoma (PDAC) cell growth is dependent on altered biochemical and cellular activities that facilitate increased metabolic dependencies. We determined the role of mutationally activated KRAS, found in ~95% PDAC, supporting autophagy. Surprisingly, acute KRAS suppression, which blocks proliferation, was associated with rather than decreased autophagic flux. Similarly, transformation immortalized human pancreatic epithelial cells showed Pharmacologic...
We show that inactivating AMPK in a genetic medulloblastoma model depletes tumor stem cells and slows progression. In medulloblastoma, the most common malignant pediatric brain tumor, drug-resistant co-exist with transit-amplifying terminally differentiated neuronal progeny. Prior studies Hk2-dependent glycolysis promotes progression by suppressing neural differentiation. To determine how metabolic regulator affects growth differentiation, we inactivated genetically medulloblastomas. bred...
Autotrophic microalgae are a promising bioproducts platform. However, the fundamental requirements these organisms have for nitrogen fertilizer severely limit impact and scale of their cultivation. As an alternative to inorganic fertilizers, we investigated possibility using amino acids from deconstructed biomass as source in genus Dunaliella. We found that only four (glutamine, histidine, cysteine, tryptophan) rescue Dunaliella spp. growth depleted media, supplementation altered metabolic...
Many oxygen mass-transfer modeling studies have been performed for various bioartificial liver (BAL) encapsulation types; yet, to our knowledge, there is no experimental study that directly and noninvasively measures viability metabolism as a function of time concentration. We report the effect concentration on in fluidized-bed NMR-compatible BAL using vivo ³¹P ¹³C NMR spectroscopy, respectively, by monitoring nucleotide triphosphate (NTP) ¹³C-labeled nutrient metabolites, respectively....
Metabolism represents interconnected networks of metabolite consumption and creation. The field metabolomics is focused on concentrations in metabolic networks. Fluxomics quantifies the flux substrate through each reaction step or a series steps required for energy balance equations system. Quantifying every pathway unnecessary because there at least one regulatory enzyme per pathway. Hence, to predict intermediate pathways, silico models typically use total merged with literature derived...
The successful applications of magnetic resonance imaging (MRI) in medicine are mostly due to the non-invasive and non-destructive nature MRI techniques. Longitudinal studies humans animals easily accomplished, taking advantage fact that does not use harmful radiation would be needed for plain film radiographic, computerized tomography (CT) or positron emission (PET) scans. Routine anatomic functional using strong signal from most abundant nucleus, proton, can also provide metabolic...
Abstract We report a novel, nanoparticle formulation of the SHH pathway inhibitor vismodegib that improves efficacy for medulloblastoma treatment while reducing toxicity. Systemic therapies brain tumors are complicated by restricted blood-brain barrier (BBB) permeability and dose-limiting extraneural toxicity, therefore improved delivery approached needed. Here we show how system addresses these obstacles, bringing new to previously ineffective therapy. Vismodegib has been promising agent...