A5023022341- Nanoplatforms for cancer theranostics
- Glioma Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Protein Kinase Regulation and GTPase Signaling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer, Hypoxia, and Metabolism
- Melanoma and MAPK Pathways
- Wnt/β-catenin signaling in development and cancer
- Immune cells in cancer
- Cancer-related Molecular Pathways
- Cell Adhesion Molecules Research
- Microtubule and mitosis dynamics
- Cell death mechanisms and regulation
- Genomics, phytochemicals, and oxidative stress
- Protein Tyrosine Phosphatases
- Biotin and Related Studies
- Cancer Cells and Metastasis
- Protease and Inhibitor Mechanisms
- Linguistic research and analysis
- Dental Trauma and Treatments
- dental development and anomalies
- Neurogenesis and neuroplasticity mechanisms
- Pentecostalism and Christianity Studies
- PI3K/AKT/mTOR signaling in cancer
- Religion, Theology, and Education
Neurobehavioral Systems
2022-2023
Intel (United States)
2021
University of California, Los Angeles
2015-2020
University of Virginia
2008-2014
Moores Cancer Center
2013
University of California, San Diego
2012
There is considerable interest in defining the metabolic abnormalities of IDH mutant tumors to exploit for therapy. While most studies have attempted discern function by using cell lines transduced with exogenous enzyme, this study, we perform unbiased metabolomics discover differences between a cohort patient-derived IDH1 and wildtype gliomaspheres.Using both our own microarray TCGA datasets, performed KEGG analysis define pathways differentially enriched cells tumors. Liquid chromatography...
The cytokinetic furrow (CF) is organized by the RhoA GTPase, which recruits actin and myosin II to drives contractility. Here we show a role for RhoGAP, p190, in cytokinesis its involvement regulating Rho GTP levels Cells depleted of p190RhoGAP (p190) accumulate high RhoGTP markers activity furrow, resulting failure CF progress abscission. loss p190 can be rescued low dose inhibitor blebbistatin, suggesting that cells fail because they have too much activity. binds organizer anillin, mutants...
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...
Abstract Background The intestinal crypt homeostasis is maintained by a combination of growth factors including Wnt, R-Spondin1, Noggin and the epidermal factor (EGF). In human colorectal cancer, Wnt pathway constitutively activated through genetic epigenetic alterations in as many 11 genes encoding components this stem-cell maintenance mechanism. Although proliferation colon cancer cells does not require it possible that can still respond to colonic microenvironment. A number studies have...
The Wnt/β-catenin pathway is constitutively activated in more than 90% of human colorectal cancer. Activated β-catenin stimulates cell proliferation and survival, however, its antiapoptotic mechanisms are not fully understood. We show here that required to suppress caspase-8 activation, but only colon cancer cells resistant tumor necrosis factor-α (TNF)-induced apoptosis. found lysosomal delivery internalized TNF occurred at a faster pace apoptosis-resistant apoptosis-sensitive cells....
Aims: The goal of this study was to determine whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-produced reactive oxygen species (ROS) enhance brain tumor growth glioblastoma (GBM) under hypoxic conditions and during radiation treatment. Results: Exogenous ROS promoted in gliomasphere cultures that expressed functional tensin homolog (PTEN), but not tumors were PTEN deficient. Hypoxia induced the production endogenous cytoplasmic cell via activation NOX. NOX resulted...
Lynch syndrome (LS), is an autosomal dominant disorder predisposing patients to multiple cancers, predominantly colorectal (CRC) and endometrial, implicated in 2-4% of all CRC cases. LS characterized by mutations four mismatch repair (MMR) genes which code for proteins responsible recognizing repairing DNA lesions occurring through mechanisms including oxidative stress (OS). Increased OS can cause considered carcinogenic. Due reduced MMR activity, have increased risk cancer as a result...
Abstract Fatty acids are well known as important constituents for the synthesis of membrane lipids and sources cellular energy in CNS. However, fatty can also act vital second messenger molecules nervous system regulate activity many proteins affecting cell growth survival. Here, we show that an essential dietary acid, Decosahexaenoic (DHA), enhance stem function vitro vivo. We found this effect is not due to increase overall proliferation rate all neural progenitors, but number multipotent...
Radiation is a mainstay of treatment for glioblastoma (GBM). While all the effects radiation are not known, it thought to induce cell death by increasing production reactive oxygen species (ROS). High amounts ROS known death, however recent data suggests that moderate increase in can promote proliferation, migration, tumorigenesis, and stem maintenance. We have found primary patient-derived gliomasphere lines both exogenous endogenous oxidizes PTEN, resulting Akt activation increased...
TMIC-16. NOX GENERATED REACTIVE OXYGEN SPECIES PROMOTES GLIOBLASTOMA GROWTH AND SURVIVAL THROUGH INACTIVATION OF PTEN Kirsten Ludwig and Harley Kornblum; University of California, Los Angeles, CA, USA is inactivated in 40% glioblastoma (GBM), however almost all GBM’s have increased Akt activity, regardless status. Treatment with exogenous reactive oxygen species (ROS) inactivates through oxidation, suggesting that a similar event may occur the hypoxic tumor environment. Recent data indicate...
Abstract The tumor suppressor protein Phosphatase and Tensin Homolog (PTEN) is a negative regulator of the Akt pathway which promotes proliferation, migration, self-renewal. PTEN mutated or deleted in ~40% glioblastoma (GBM) resulting increased activity; however almost all GBM's have activity, regardless status. This raises possibility that GBM may inactivate through means other than mutation deletion. Treatment with exogenous reactive oxygen species (ROS), like hydrogen peroxide,...
p190RhoGAP (p190) is a RhoGTPase activator protein (GAP) that has been shown to regulate actin cytoskeletal dynamics via Rho‐dependent signaling pathways. By enhancing Rho‐mediated hydrolysis of RhoGTP RhoGDP, p190 negatively regulates association with its downstream effectors. The gene located on chromosome 19q13.3, which mutated in several solid tumor types, suggesting involvement malignant transformation. Findings reduced the incidence PDGF‐induced gliomas mouse models further implicate...
Thursday, April 30April 14, 2020Free AccessiPSC-generated motor neurons from patients with PTEN deficiency as a model to elucidate mechanisms underlying aberrant circuit development in autism spectrum disorder (2907)Michelle Allen-sharpley, Raymond Gau, Kirsten Ludwig, Michael Condro, Julian Martinez Agosto, Dhruv Sareen, and Harley KornblumAuthors Info & AffiliationsApril 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.2907 Letters the Editor
ABSTRACT Aims The goal of this study was to determine whether NADPH oxidase (NOX)-produced reactive oxygen species enhances brain tumor growth glioblastoma (GBM) under hypoxic conditions and during radiation treatment. Results Exogenous ROS promoted in gliomasphere cultures that expressed functional PTEN, but not tumors were PTEN deficient. Hypoxia induced the production endogenous cytoplasmic cell via activation NOX. NOX resulted oxidation downstream Akt activation. Radiation also which,...