A5081200258- Glioma Diagnosis and Treatment
- Cancer Cells and Metastasis
- Microtubule and mitosis dynamics
- Neurogenesis and neuroplasticity mechanisms
- MicroRNA in disease regulation
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Cell Image Analysis Techniques
- Cancer Mechanisms and Therapy
- Neuroblastoma Research and Treatments
- Immune cells in cancer
- Melanoma and MAPK Pathways
- interferon and immune responses
- Cancer Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Neuroinflammation and Neurodegeneration Mechanisms
- Protein Degradation and Inhibitors
- Hippo pathway signaling and YAP/TAZ
- Radiomics and Machine Learning in Medical Imaging
- Cell death mechanisms and regulation
- Angiogenesis and VEGF in Cancer
- Epigenetics and DNA Methylation
- Protein Kinase Regulation and GTPase Signaling
- Cellular Mechanics and Interactions
Stanford University
2020-2025
Palo Alto University
2021-2024
Neurological Surgery
2011-2022
Palo Alto Institute
2021
University of California, San Francisco
2010-2019
City College of San Francisco
2012-2018
Broad Center
2011-2018
UCSF Helen Diller Family Comprehensive Cancer Center
2008-2018
Cancer Research Center
2015-2016
Helmholtz Zentrum München
2013
Abstract Background Glioblastoma multiforme (GBM) is an invariably fatal central nervous system tumor despite treatment with surgery, radiation, and chemotherapy. Further insights into the molecular cellular mechanisms that drive GBM formation are required to improve patient outcome. MicroRNAs emerging as important regulators of differentiation proliferation, have been implicated in etiology a variety cancers, yet role microRNAs remains poorly understood. In this study, we investigated...
On TGF-β binding, the receptor directly phosphorylates and activates transcription factors Smad2/3, leading to G 1 arrest. Here, we present evidence for a second, parallel, TGF-β-dependent pathway cell cycle arrest, achieved via inhibition of p70 s6k . induces association its with protein phosphatase-2A (PP2A)-Bα. Concomitantly, three PP2A-subunits, Bα, Aβ, Cα, associate , dephosphorylation inactivation. Although either is sufficient induce abrogation both, through Smad proteins required...
Several cancer types consist of multiple genetically and phenotypically distinct subpopulations. The underlying mechanism for this intra-tumoral heterogeneity can be explained by the clonal evolution model, whereby growth advantageous mutations cause expansion cell subclones. recurrent phenotype many cancers may a consequence these coexisting subpopulations responding unequally to therapies. Methods computationally infer tumor subpopulation diversity are emerging they hold promise improve...
This clinical trial evaluated whether whole exome sequencing (WES) and RNA (RNAseq) of paired normal tumor tissues could be incorporated into a personalized treatment plan for newly diagnosed patients (<25 years age) with diffuse intrinsic pontine glioma (DIPG). Additionally, genome (WGS) was compared to WES determine if WGS would further inform decisions, circulating DNA (ctDNA) detect the H3K27M mutation allow assessment therapy response. Patients were selected across three Pacific...
Glioblastoma multiforme (GBM) is one the most aggressive brain tumors due to fast and invasive growth that partly supported by presence of extensive neovascularization. The matrix metalloproteinase MMP-2 has been associated with angiogenic properties in gliomas a marker poor prognosis. Since expressed both tumor cells endothelial GBM, we generated genetically engineered knockout (MMP-2ko) GBM examine importance spatial expression and/or normal host-derived cells. MMP-2–dependent effects...
Although malignant astrocytomas are a leading cause of cancer-related death in children, rational therapeutic strategies lacking. We previously identified activating mutations v-raf murine sarcoma viral oncogene homolog B1 ( BRAF ) T1799A encoding V600E association with homozygous cyclin-dependent kinase inhibitor 2A CDKN2A , p14ARF and p16Ink4a deletions pediatric infiltrative astrocytomas. Here we report that expression neural progenitors (NPs) is insufficient for tumorigenesis increases...
The exquisite sensitivity of mitotic cancer cells to ionizing radiation (IR) underlies an important rationale for the widely used fractionated therapy. However, mechanism this cell cycle-dependent vulnerability is unknown. Here we show that treatment with IR leads chromosome segregation errors in vivo and long-lasting aneuploidy tumour-derived lines. These generate abundance micronuclei predispose chromosomes subsequent catastrophic pulverization thereby independently amplifying...
We show here using synchronized Swiss mouse 3T3 fibroblasts that p70 S6 kinase (p70S6k) and mitogen-activated protein kinases (p42mapk/p44mapk) are not only activated at the G0/G1 boundary, but also in cells progressing from M into G1. p70S6k activity increases 20-fold G1 released G0. Throughout G1, S, G2 it decreases constantly, so during phase low is measured. The reactivated 10-fold when a nocodazole-induced metaphase block enter of next cell cycle. p42mapk/p44mapk G0 transiently early...
Abstract Purpose: Alteration of the BRAF/MEK/MAPK pathway is hallmark pediatric low-grade gliomas (PLGGs), and mTOR activation has been documented in majority these tumors. We investigated combinations MEK1/2, BRAFV600E inhibitors carrying specific genetic alterations MAPK pathway. Experimental Design: used human glioma lines containing (adult high-grade: AM-38, DBTRG, PLGG: BT40), or wild-type BRAF (pediatric SF188, SF9427, SF8628) isogenic systems KIAA1549:BRAF-expressing NIH/3T3 cells...
Abstract The treatment of glioblastoma (GBM) remains challenging in part due to the presence stem-like tumor-propagating cells that are resistant standard therapies consisting radiation and temozolomide. Among novel targeted agents under evaluation for GBM BRAF/MAPK inhibitors, but their effects on unclear. Here, we characterized behaviors CD133+ isolated from primary cell lines. We show exhibited decreased sensitivity antiproliferative inhibition compared CD133− cells. Furthermore, an...
Drosophila neuroblasts have served as a model to understand how the balance of stem cell self-renewal versus differentiation is achieved. Numb protein regulates this process through its preferential segregation into differentiating daughter cell. How restricts proliferation and potentials recipient remains enigmatic. Here, we show that phosphorylation at conserved sites tumor suppressor activity Numb. Enforced expression phospho-mimetic form (Numb-TS4D) or genetic manipulation boosts...
Inhibitors of BRAFV600E kinase are currently under investigations in preclinical and clinical studies involving glioma. Studies demonstrated response to such individualized therapy the majority patients whereas some tumors continue grow despite treatment. To study resistance mechanisms, which include feedback activation mitogen-activated protein (MAPK) signaling melanoma, we developed a luciferase-modified cell line (2341luc) from BrafV600E mutant Cdkn2a- deficient murine high-grade glioma,...
The adaptor protein Miranda plays a pivotal role in the asymmetric cell division of neuroblasts by asymmetrically segregating key differentiation factors. localization requires Myosin VI and II. apical-then-basal pattern detected fixed tissue, defects embryos lacking VI, suggest that is transported to basal pole as cargo. However, mode temporal sequence have not been characterized live embryos. Furthermore, it unknown whether PON, second required for localization, are both regulated By...