Ayesha U. Kothari
A5084500393- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Biochemical and Molecular Research
- Cancer Research and Treatments
- DNA Repair Mechanisms
- Estrogen and related hormone effects
- Vitamin C and Antioxidants Research
- Mitochondrial Function and Pathology
- Prostate Cancer Treatment and Research
- Epigenetics and DNA Methylation
- Amino Acid Enzymes and Metabolism
- GABA and Rice Research
- bioluminescence and chemiluminescence research
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Genomics, phytochemicals, and oxidative stress
- Cancer-related Molecular Pathways
- Global Health Workforce Issues
- Advances in Oncology and Radiotherapy
- Metabolomics and Mass Spectrometry Studies
- Metabolism, Diabetes, and Cancer
- CRISPR and Genetic Engineering
- Diet and metabolism studies
- Metabolism and Genetic Disorders
University of Michigan
2020-2024
Michigan State University
2023
Abstract Background Diffuse midline gliomas (DMG), including diffuse intrinsic pontine (DIPGs), are a fatal form of brain cancer. These tumors often carry driver mutation on histone H3 converting lysine 27 to methionine (H3K27M). DMG-H3K27M characterized by altered metabolism and resistance standard care radiation (RT) but how the H3K27M mediates metabolic response consequent treatment is uncertain. Methods We performed metabolomics irradiated untreated isogenic DMG cell lines observed an...
How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links to and has significant therapeutic implications. GTP, but not other nucleotides, the activity of Rac1, guanine nucleotide-binding protein, which promotes dephosphorylation serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5). Dephosphorylated Abi-1, previously known activate repair, nonhomologous end joining. In patients mouse models glioblastoma,...
New approaches are needed to overcome intrinsic therapy resistance in glioblastoma (GBM). Because GBMs exhibit sexual dimorphism and reported express steroid hormone receptors, we reasoned that signaling through the androgen receptor (AR) could mediate GBM, much as it does AR-positive prostate breast cancers. We found nearly half of GBM cell lines, patient-derived xenografts (PDX), human tumors expressed AR at transcript protein level-with expression levels overlapping those primary cancer....
ABSTRACT Glioblastoma (GBM) is uniformly lethal due to profound treatment resistance. Altered cellular metabolism a key mediator of GBM Uptake the essential sulfur-containing amino acid methionine drastically elevated in GBMs compared normal cells, however, it not known how this utilized or whether relates Here, we find that radiation acutely increases levels methionine-related metabolites variety treatment-resistant models. Stable isotope tracing studies further revealed activates...
Abstract The brain avidly consumes glucose to fuel neurophysiology. Cancers of the brain, such as glioblastoma (GBM), lose aspects normal biology and gain ability proliferate invade healthy tissue. How cancers rewire utilization these processes is poorly understood. Here we perform infusions 13 C-labeled into patients mice with cancer define metabolic fates glucose-derived carbon in tumor cortex. By combining measurements quantitative flux analysis, find that human cortex funnels carbons...
Abstract Glioblastoma (GBM) is the most aggressive adult brain tumor and uniformly fatal due to resistance standard therapies such as radiation (RT) chemotherapy. Our group others have identified altered metabolism a key mediator of GBM RT resistance. Methionine an essential sulfur-containing amino acid that cells use synthesize antioxidants, polyamines S-adenosyl methionine (SAM), which drives intracellular methylation reactions. uptake dramatically elevated in compared normal brain, but...
<p>Supplementary Data 1 shows the original data of phosphoproteomic assay in Figure 2.</p>
<p>Supplementary Data 2 shows Supplementary Methods, Reference, Figure S1 and Legends, S2 S3 S4 S5 S6 S7 Legends.</p>
<p>Supplementary Data 2 shows Supplementary Methods, Reference, Figure S1 and Legends, S2 S3 S4 S5 S6 S7 Legends.</p>
<div>ABSTRACT<p>How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links to and has significant therapeutic implications. GTP, but not other nucleotides, the activity of Rac1, guanine nucleotide-binding protein, which promotes dephosphorylation serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5). Dephosphorylated Abi-1, previously known activate repair, nonhomologous end joining. In patients...
<div>ABSTRACT<p>How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links to and has significant therapeutic implications. GTP, but not other nucleotides, the activity of Rac1, guanine nucleotide-binding protein, which promotes dephosphorylation serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5). Dephosphorylated Abi-1, previously known activate repair, nonhomologous end joining. In patients...
<p>Supplementary Data 1 shows the original data of phosphoproteomic assay in Figure 2.</p>
Abstract OBJECTIVE: We sought to define the mechanisms by which purines regulate DNA repair and therapy response. METHODS: Phosphoproteomics was used identify GTP-dependent (de)phosphorylation events after radiation (RT) antibodies generated against novel sites. Animal models of glioblastoma (GBM) normal tissues were assess treatment responses in vivo. RESULTS: Pharmacogenomic inhibition GTP (but not ATP) synthesis sensitized GBM cells RT inhibiting activity non-homologous end joining, but...
Abstract Metabolic adaptation can promote oncogenic phenotypes in glioblastoma (GBM), but the metabolic pathways utilized by GBM and how they differ from normal cortex are poorly understood. Here, we utilize vivo stable isotope tracing mice patients with to define carbon fate rewiring cancer. We infused uniformly labeled 13C glucose into bearing orthotopic patient-derived xenografts or undergoing surgical resection for likely GBM. Tumor were physically separated fluorescence-guided...
Abstract Glioblastoma (GBM) is the most common type of invasive brain tumor in adults and uniformly fatal due to inherent resistance radiation therapy (RT) chemotherapy. Our group others have found that metabolites can regulate DNA repair tumors, but little known about how damage regulates metabolic pathway activity cancer. Here we show following treatment with RT, GBMs increase rates de novo guanylate synthesis vitro orthotopic patient-derived xenograft models via signaling through protein...
Abstract The brain avidly consumes glucose to fuel neurophysiology. Cancers of the brain, such as glioblastoma (GBM), lose aspects normal biology and gain ability proliferate invade healthy tissue. How cancers rewire utilization these processes is poorly understood. Here we perform infusions 13C-labeled into patients mice with cancer define metabolic fates glucose-derived carbon in tumor cortex. By combining measurements quantitative flux analysis, find that human cortex funnels carbons...
Abstract The brain avidly consumes glucose to fuel neurophysiology. Cancers of the brain, such as glioblastoma (GBM), lose aspects normal biology and gain ability proliferate invade healthy tissue. How cancers rewire utilization these processes is poorly understood. Here we perform infusions 13C-labeled into patients mice with cancer define metabolic fates glucose-derived carbon in tumor cortex. By combining measurements quantitative flux analysis, find that human cortex funnels carbons...
Abstract Glioblastoma (GBM) is uniformly lethal due to profound treatment resistance. Altered cellular metabolism a key mediator of GBM Uptake the essential sulfur-containing amino acid methionine drastically elevated in GBMs compared normal cells, however, it not known how this utilized or whether relates resistance.Here, we find that radiation acutely increases levels methionine-related metabolites variety treatment-resistant models. Stable isotope tracing studies further revealed...
Gender inequity in medicine harms society, and often originates the context of broader societal discrimination. This study explores experiences older women radiation oncology specialty Japan United States, with an emphasis on understanding how gender affects career trajectory. Radiation is ideal setting to investigate cross-cultural physician equity issues, because few enter field despite fewer barriers (eg, frequent emergencies, evening/weekend hours, long procedures) that are commonly...
Abstract Glioblastoma (GBM) is uniformly fatal due to inherent radiation (RT) and chemotherapy resistance. We have found this therapeutic resistance mediated by alterations in tumor cellular metabolic activity. Our group others that metabolites can regulate DNA repair RT brain tumors, but little known about how damage regulates pathway activity cancer. Here, we show acutely increases guanine-containing purine multiple vitro intracranial GBM models. By interrogating fluxes using a variety of...
Abstract Introduction/Objectives: Purines regulate DNA repair in brain tumors through uncertain mechanisms. We sought to define the mechanisms by which purines and therapy response. Methods: Crispr/Cas9, siRNA, CDNA overexpression immunoblot were used modulate confirm protein levels. γ-H2AX Rad51 foci enumerated using immunofluorescence. Fluorescent reporter assays performed detect activity. Phosphoproteomics was identify GTP-dependent (de)phosphorylation events after RT antibodies generated...
<p>Supplementary Figure S1: Additional expression data and comparisons of AR by subtype, age, sex, common molecular alterations. Supplementary S2. Tumor growth plots mice weights for in vivo studies. S3: Heat map down-regulated genes from the GBM 26 RNA-seq experiment. S4: Effects seviteronel on dsDNA break repair AR-positive negative models post-radiation. S5: enzalutamide S6. alkaline tail moment Method: comet assay.</p>
<p>Supplementary Figure S1: Additional expression data and comparisons of AR by subtype, age, sex, common molecular alterations. Supplementary S2. Tumor growth plots mice weights for in vivo studies. S3: Heat map down-regulated genes from the GBM 26 RNA-seq experiment. S4: Effects seviteronel on dsDNA break repair AR-positive negative models post-radiation. S5: enzalutamide S6. alkaline tail moment Method: comet assay.</p>