A5045676945- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Mechanisms of cancer metastasis
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Melanoma and MAPK Pathways
- Ferroptosis and cancer prognosis
- Computational Drug Discovery Methods
- Cancer Mechanisms and Therapy
- Radiopharmaceutical Chemistry and Applications
- Cutaneous Melanoma Detection and Management
- Cancer Research and Treatments
- Prostate Cancer Treatment and Research
- CRISPR and Genetic Engineering
- Nanoparticles: synthesis and applications
- 3D Printing in Biomedical Research
- Cellular Mechanics and Interactions
- Cancer Cells and Metastasis
- Angiogenesis and VEGF in Cancer
- Glioma Diagnosis and Treatment
- Cancer Treatment and Pharmacology
- Cancer, Lipids, and Metabolism
- SARS-CoV-2 and COVID-19 Research
- Mitochondrial Function and Pathology
University of California, Los Angeles
2016-2025
California NanoSystems Institute
2016-2025
Samueli Institute
2020-2025
UCLA Jonsson Comprehensive Cancer Center
2018-2025
UCLA Medical Center
2017-2025
Broad Center
2012-2025
Lund University
2023
Los Angeles Medical Center
2017-2021
University of Colorado Denver
2018-2021
University of Colorado Cancer Center
2018-2021
PD-L1 and PD-L2 are ligands for the PD-1 immune inhibiting checkpoint that can be induced in tumors by interferon exposure, leading to evasion. This process is important immunotherapy based on blockade. We examined specific molecules involved interferon-induced signaling regulates expression melanoma cells. These studies revealed interferon-gamma-JAK1/JAK2-STAT1/STAT2/STAT3-IRF1 axis primarily expression, with IRF1 binding its promoter. responded equally beta gamma regulated through both...
We demonstrate for 24 metal oxide (MOx) nanoparticles that it is possible to use conduction band energy levels delineate their toxicological potential at cellular and whole animal levels. Among the materials, overlap of (Ec) with redox (−4.12 −4.84 eV) was strongly correlated ability Co3O4, Cr2O3, Ni2O3, Mn2O3, CoO induce oxygen radicals, oxidative stress, inflammation. This outcome premised on permissible electron transfers from biological couples maintain equilibrium semiconductor...
The establishment of verifiably safe nanotechnology requires the development assessment tools to identify hazardous nanomaterial properties that could be modified improve safety. While there is a lot debate what constitutes appropriate safety screening methods, one approach use cellular injury pathways collect knowledge about material lead harm humans and environment. We demonstrate multiparameter cytotoxicity assay evaluates toxic oxidative stress compare effects titanium dioxide (TiO2),...
Because of concerns about the safety a growing number engineered nanomaterials (ENM), it is necessary to develop high-throughput screening and in silico data transformation tools that can speed up vitro hazard ranking. Here, we report use multiparametric, automated assay incorporates sublethal lethal cellular injury responses perform analysis batch commercial metal/metal oxide nanoparticles (NP) with inclusion quantum dot (QD1). The chosen for tracking through epifluorescence microscopy...
Abstract Tumor organoids maintain cell–cell interactions, heterogeneity, microenvironment, and drug response of the sample they originate from. Thus, there is increasing interest in developing tumor organoid models for development personalized medicine applications. Although are principle amenable to high-throughput screenings, progress has been hampered by technical constraints extensive manipulations required current methods. Here we introduce a miniaturized method that uses simplified...
Abstract Viruses hijack host cell metabolism to acquire the building blocks required for replication. Understanding how SARS-CoV-2 alters may lead potential treatments COVID-19. Here we profile metabolic changes conferred by infection in kidney epithelial cells and lung air-liquid interface (ALI) cultures, show that increases glucose carbon entry into TCA cycle via increased pyruvate carboxylase expression. also reduces oxidative glutamine while maintaining reductive carboxylation....
We describe an antiviral small molecule, LJ001, effective against numerous enveloped viruses including Influenza A, filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses, flaviviruses, and HIV-1. In sharp contrast, the compound had no effect on infection of nonenveloped viruses. vitro in vivo assays showed overt toxicity. LJ001 specifically intercalated into viral membranes, irreversibly inactivated virions while leaving functionally intact envelope proteins, inhibited entry...
The stability and bioavailability of nanoparticles is governed by the interfacial properties that acquire when immersed in a particular aquatic media as well type organism or cell under consideration. Herein, high-throughput screening (HTS) was used to elucidate ZnO nanoparticle stability, bioavailability, antibacterial mechanisms function iron doping level (in nanoparticles), chemistry, bacterial type. ζ-Potential aggregation state dispersed strongly influenced addition electrolyte...
Although silver nanoparticles are being exploited widely in antimicrobial applications, the mechanisms underlying nanoparticle properties environmentally relevant media not fully understood. The latter point is critical for understanding potential environmental impacts of nanoparticles. aim this study was to elucidate influence inorganic aquatic chemistry on stability (aggregation, dissolution, reprecipitation) and bacterial viability. A synthetic "fresh water" matrix prepared comprising...
Zebrafish is an aquatic organism that can be used for high content safety screening of engineered nanomaterials (ENMs). We demonstrate, the first time, use bright-field and fluorescence-based imaging to compare toxicological effect transition metal oxide (CuO, ZnO, NiO, Co(3)O(4)) nanoparticles in zebrafish embryos larvae. High demonstrated potent dose-dependent hatching interference embryos, with exception Co(3)O(4) which was relatively inert. propose due shedding Cu Ni ions, compromising...
High-throughput screening was employed to evaluate bactericidal activities of hybrid Ag-TiO2 nanoparticles comprising variations in TiO2 crystalline phase, Ag content, and synthesis method. Hybrid were prepared by either wet-impregnation or UV photo deposition onto both Degussa P25 DuPont R902 nanoparticles. The presence confirmed ICP, TEM, XRD analysis. size formed on anatase/rutile smaller than those pure rutile R902. When activated light, all exhibited stronger activity alone, Ag/UV,...
Treatment of advanced
The zebrafish is emerging as a model organism for the safety assessment and hazard ranking of engineered nanomaterials. In this Communication, implementation roboticized high-throughput screening (HTS) platform with automated image analysis demonstrated to assess impact dissolvable oxide nanoparticles on embryo hatching. It further that hatching interference mechanistically linked an effect metalloprotease, ZHE 1, which responsible degradation chorionic membrane. data indicate 4 24 metal...
Interferon-independent MHC class I induction restores T cell immunity.
SARS-CoV-2 has currently precipitated the COVID-19 global health crisis. We developed a medium-throughput drug-screening system and identified small-molecule library of 34 430 protein kinase inhibitors that were capable inhibiting cytopathic effect in human epithelial cells. These drug are various stages clinical trials. detected key proteins involved cellular signaling pathways mTOR-PI3K-AKT, ABL-BCR/MAPK, DNA-damage response critical for infection. A drug-protein interaction-based...
Melanoma resistant to MAPK inhibitors (MAPKi) displays loss of fitness upon experimental MAPKi withdrawal and, clinically, may be resensitized therapy after a drug holiday. Here, we uncovered and therapeutically exploited the mechanisms addiction in MAPKi-resistant
Significance COVID-19 is taking a major toll on personal health, healthcare systems, and the global economy. With three betacoronavirus epidemics in less than 20 y, there an urgent need for therapies to combat new existing coronavirus outbreaks. Our analysis of clinical data from over 300,000 patients health systems demonstrates 50% reduced risk lithium, direct inhibitor glycogen synthase kinase-3 (GSK-3). We further show that GSK-3 essential phosphorylation SARS-CoV-2 nucleocapsid protein...