A5027353457- RNA modifications and cancer
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Cancer, Hypoxia, and Metabolism
- Genetics and Neurodevelopmental Disorders
- Advanced biosensing and bioanalysis techniques
- Bioinformatics and Genomic Networks
- Cell Image Analysis Techniques
- 3D Printing in Biomedical Research
- Neurogenesis and neuroplasticity mechanisms
- RNA Research and Splicing
- Protein Degradation and Inhibitors
- Cancer, Lipids, and Metabolism
- Mercury impact and mitigation studies
- Heavy Metal Exposure and Toxicity
- Cancer-related Molecular Pathways
- Innovative Microfluidic and Catalytic Techniques Innovation
- Cancer Research and Treatments
- Computational Drug Discovery Methods
- Barrier Structure and Function Studies
- Radiomics and Machine Learning in Medical Imaging
- Caveolin-1 and cellular processes
Voyager Therapeutics (United States)
2021-2023
Memorial Sloan Kettering Cancer Center
2018-2022
Neurobehavioral Systems
2020-2021
University of California, Los Angeles
1990-2021
Cancer Genetics (United States)
2020
Kettering University
2018
Broad Center
2016
UCLA Medical Center
2010-2014
The Lundquist Institute
2014
Harbor–UCLA Medical Center
2014
Renewable neurosphere formation in culture is a defining characteristic of certain brain tumor initiating cells. This retrospective study was designed to assess the relationship among cultured human glioma, tumorigenic capacity, and patient clinical outcome. Tumor samples were conditions from 32 patients with including subpopulation 15 primary glioblastoma. A subsample renewable cultures xenografted into mouse determine if they tumorigenic. Our shows that both capacity are significantly...
A period of mild brain overgrowth with an unknown etiology has been identified as one the most common phenotypes in autism. Here, we test hypothesis that maternal inflammation during critical periods embryonic development can cause and autism-associated behaviors a result altered neural stem cell function. Pregnant mice treated low-dose lipopolysaccharide at day 9 had offspring overgrowth, more pronounced effect PTEN heterozygotes. Exposure to also enhanced NADPH oxidase (NOX)-PI3K pathway...
Gliomasphere cultures are widely utilized for the study of glioblastoma (GBM). However, this model system is not well characterized, and utility current classification methods clear. We used 71 gliomasphere from 68 individuals. Using gene expression-based classification, we performed unsupervised clustering associated expression with phenotypes patient survival. Some aspects method were robust because retained their over many passages, IDH1 mutant gliomaspheres all proneural. While a subset...
The clinical practice of oncology is being transformed by molecular diagnostics that will enable predictive and personalized medicine. Current technologies for quantitation the cancer proteome are either qualitative (e.g., immunohistochemistry) or require large sample sizes flow cytometry). Here, we report a microfluidic platform-microfluidic image cytometry (MIC)-capable quantitative, single-cell proteomic analysis multiple signaling molecules using only 1,000 to 2,800 cells. Using cultured...
Significance Adult neural stem cells (NSC) are closely related to multiple neurological disorders and brain tumors. Comprehensive investigation of their composition, lineage, aging will provide insights that may lead enhanced patient treatment. This study applies a transgene label manipulate stem/progenitor monitor evolution during aging. Together with high-throughput single-cell RNA sequencing, we able analyze the subventricular zone from infancy advanced age unprecedented granularity....
Abstract Targeting amino acid metabolism has therapeutic implications for aggressive brain tumors. Asparagine is an that synthesized by normal cells. However, some cancer cells lack asparagine synthetase (ASNS), the key enzyme synthesis. Asparaginase (ASNase) contributes to eradication of acute leukemia decreasing levels in serum and cerebrospinal fluid. leukemic may become ASNase-resistant upregulating ASNS. High expression ASNS also been associated with biologic aggressiveness other...
Glioblastoma multiforme (GBM) is a devastating disease, and the current therapies have only palliative effect. Evidence mounting to indicate that brain tumor stem cells (BTSCs) are minority of responsible for cancer initiation, propagation, maintenance. Therapies fail eradicate BTSCs may ultimately lead regrowth residual BTSCs. However, relatively resistant treatments. Development novel therapeutic strategies effectively BTSC are, therefore, essential. In previous study, we used...
Abstract Background Cultured brain tumors can form neurospheres harboring tumorigenic cells with self renewal and differentiation capacities. Renewable neurosphere formation has clinical predictive value in adult malignant gliomas, yet its prognostic role for pediatric is unknown. Methods Established conditions were used culturing samples from glial, embryonal mixed glioneuronal 56 patients. Potential associations between outcome analyzed retrospectively. Results Thirty‐seven percent of all...
Glioblastoma (GBM) is characterized by extensive microvascular hyperproliferation. In addition to supplying blood the tumor, GBM vessels also provide trophic support glioma cells and serve as conduits for migration into surrounding brain, promoting recurrence. Here, we enrich CD31-expressing vascular (GVCs) A2B5-expressing tumor (GTCs) from primary use RNA sequencing create a comprehensive molecular interaction map of secreted extracellular factors elaborated GVCs that can interact with...
Clinical trials of therapies directed against nodes the signaling axis phosphatidylinositol-3 kinase/Akt/mammalian target rapamycin (mTOR) in glioblastoma (GBM) have had disappointing results. Resistance to mTOR inhibitors limits their efficacy.To determine mechanisms resistance chronic inhibition, we performed tandem screens on patient-derived GBM cultures.An unbiased phosphoproteomic screen quantified phosphorylation changes associated with exposure inhibitor rapamycin, and our analysis...
GH is first detectable in the fetal rat pituitary between gestational days 18 and 19. The reasons for surge soon after birth subsequent postnatal decline to adult levels remain unclear. We therefore determined whether gene regulation developing could be distinguished from somatotroph function. In primary cultures of neonatal cells, secretion was detected by 20th day. These cells were stimulated GH-releasing hormone (GHRH), but not T3 or morphogen retinoic acid. stimulatory effect (0.25 HM)...
Abstract Inhibition of both the de novo (DNP) and salvage (NSP) pathways nucleoside synthesis has been demonstrated to impair leukemia cells. We endeavored determine whether this approach would be efficacious in glioblastoma. To diminish biosynthesis, we utilized compound DI-39, which selectively targets NSP, combination with thymidine (dT), DNP. employed vitro ex vivo models effects pretreatment dT + DI-39 on brain tumor stem cells (BTSC). Here, demonstrate that combinatorial therapy...
We present here a novel genetic algorithm-based random forest (GARF) modeling technique that enables reduction in the complexity of large gene disease signatures to highly accurate, greatly simplified panels. When applied 803 glioblastoma multiforme samples, this method allowed 840-gene Verhaak et al. panel (the standard field) be reduced 48-gene classifier, while retaining 90.91% classification accuracy, and outperforming best available alternative methods. Additionally, using approach we...
Background . Dose-dependent response makes certain pediatric brain tumors appropriate targets for high-dose chemotherapy with autologous hematopoietic stem-cell rescue (HDCT-AHSCR). Methods The clinical outcomes and toxicities were analyzed retrospectively 18 consecutive patients ≤19 y/o treated HDCT-AHSCR at UCLA (1999–2009). Results Patients' median age was 2.3 years. Fourteen had primary 4 recurrent tumors: 12 neural/embryonal (7 medulloblastomas, primitive neuroectodermal tumors, a...
The goals of the study were (1) to determine impact inorganic mercury exposure on glucose homeostasis; and (2) evaluate effectiveness two community-based interventions in promoting dietary changes among American Indian college students reduce risk factors for Type-2 Diabetes including fasting glucose, insulin, levels, weight, body mass index.
Analysis of tumor gene expression is an important approach for the classification and identification therapeutic vulnerabilities. However, targeting glioblastoma (GBM) based on molecular subtyping has not yet translated into successful therapies. Here, we present integrative pathways to expose new potentially actionable targets. We used set enrichment analysis conduct unsupervised clustering condense data from bulk patient samples patient-derived gliomasphere lines signatures. identified key...
Abstract The verbal interaction of 2-year-old children (N = 46; 16 girls, 30 boys) and their mothers was audiotaped, transcribed, analyzed for the use personal pronouns, total number utterances, child's mean length utterance, mother's responsiveness to her utterances. Mothers' pronoun we significantly related children's performance on Stanford-Binet at age 5 Wechsler Intelligence Scale Children 8. in social-vocal interchange, indicating a system establishing shared relationship with child,...
SummaryGlioblastoma (GBM) is characterized by extensive microvascular hyperproliferation. In addition to supplying blood the tumor, GBM vessels also provide trophic support glioma cells and serve as conduits for migration into surrounding brain promoting recurrence. Here, we enriched CD31-expressing vascular (GVC) A2B5-expressing tumor (GTC) from primary utilized RNA sequencing create a comprehensive interaction map of secreted extracellular factors elaborated GVC that can interact with...