A5066256793- interferon and immune responses
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
- Inflammasome and immune disorders
- Radiopharmaceutical Chemistry and Applications
- Immune Cell Function and Interaction
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Protein Tyrosine Phosphatases
- Ferroptosis and cancer prognosis
- Mitochondrial Function and Pathology
- Chemical Synthesis and Analysis
- Ubiquitin and proteasome pathways
- Immune Response and Inflammation
- Cell Adhesion Molecules Research
- S100 Proteins and Annexins
- Inflammatory mediators and NSAID effects
- Computational Drug Discovery Methods
- Viral Infections and Vectors
- Adipose Tissue and Metabolism
- Autophagy in Disease and Therapy
UCSF Helen Diller Family Comprehensive Cancer Center
2023-2024
University of California, San Francisco
2023-2024
Neurological Surgery
2023-2024
The University of Texas at Austin
2020-2023
City College of San Francisco
2023
Oxford University Press (United Kingdom)
2020
AbbVie (Japan)
2018-2019
AbbVie (United States)
2017-2019
Molecular Oncology (United States)
2017
Genentech
2014
The Tumor Inflammation Signature (TIS) is an investigational use only (IUO) 18-gene signature that measures a pre-existing but suppressed adaptive immune response within tumors. TIS has been shown to enrich for patients who respond the anti-PD1 agent pembrolizumab. To explore this phenotype and across tumor types, we applied algorithm over 9000 gene expression profiles downloaded from Cancer Genome Atlas (TCGA). As expected based on prior evidence, tumors with known clinical sensitivity...
Abstract Mounting evidence suggests that inhibition of protein phosphatase-2A (PP2A), a serine/threonine phosphatase, could enhance anticancer immunity. However, drugs targeting PP2A are not currently available. Here, we report inhibitor, LB-100, when combined with anti-PD-1 (aPD-1) blockade can synergistically elicit durable immune-mediated antitumor response in murine CT26 colon cancer model. This effect is T-cell dependent, leading to regression significant proportion tumors. Analysis...
Anti-cancer immunotherapy is encountering its own checkpoint. Responses are dramatic and long lasting but occur in a subset of tumors largely dependent upon the pre-existing immune contexture individual cancers. Available data suggest that three landscapes best define cancer microenvironment: <b><i>immune-active</i></b>, <b><i>immune-deserted immune-excluded</i></b>. This trichotomy observable across most solid (although frequency each landscape varies depending on tumor tissue origin)...
Glioblastoma (GBM) is an immunologically "cold" tumor that does not respond to current immunotherapy. Here, we demonstrate a fundamental role for the α-isoform of catalytic subunit protein phosphatase-2A (PP2Ac) in regulating glioma immunogenicity. Genetic ablation PP2Ac cells enhanced double-stranded DNA (dsDNA) production and cGAS-type I IFN signaling, MHC-I expression, mutational burden. In coculture experiments, deficiency promoted dendritic cell (DC) cross-presentation clonal expansion...
Stimulator of IFN genes type I (STING-Type I) signaling in myeloid cells plays a critical role effective antitumor immune responses, but STING agonists as monotherapy have shown limited efficacy clinical trials. The mechanisms that downregulate are not fully understood. Here, we report protein phosphatase 2A (PP2A), with its specific B regulatory subunit Striatin 4 (STRN4), negatively regulated STING-Type macrophages. Mice macrophage PP2A deficiency exhibited reduced tumor progression....
LPS-activated neutrophils secrete IL-1β by activation of TLR-4. Based on studies in macrophages, it is likely that ROS and lysosomal destabilization regulated Syk may also be involved. Since have abundant expression the ITIM-containing co-receptor CEACAM1 Gram-negative bacteria such as Neisseria utilize a receptor inhibits inflammation, we hypothesized overall production LPS treated negatively CEACAM1. We found induced phosphorylation resulting formation complex including TLR4, p-Syk,...
Abstract Cancer immunotherapy shows promising potential for treating breast cancer. While patients may have heterogeneous treatment responses adjuvant therapy, it is challenging to predict an individual patient’s response cancer immunotherapy. Here, we report primary tumor-derived organotypic cell clusters (POCCs) rapid and reliable evaluation of By using a label-free, contactless, highly biocompatible acoustofluidic method, hundreds could be assembled from patient tumor dissociation within...
Signaling pathways underlying BV8-mediated oncogenesis remain unknown.BV8-STAT3 forms a feed-forward loop in both normal and malignant myeloid cells promotes tumor growth.JAK2/STAT3 signaling plays critical roles cell-dependent oncogenesis.This study identifies novel role of BV8-STAT3 mediating cross-talk between microenvironment cells. An important BV8 mobilization angiogenesis has been established. Recently, it also shown that granulocyte colony-stimulating factor (G-CSF)-induced...
Abstract Human neurodegenerative disorders often exhibit similar pathologies, suggesting a shared aetiology. Key pathological features of Parkinson’s disease (PD) are also observed in other diseases. Pantothenate Kinase-Associated Neurodegeneration (PKAN) is caused by mutations the human PANK2 gene, which catalyzes initial step de novo CoA synthesis. Here, we show that fumble ( fbl ), homolog Drosophila , interacts with PINK1 genetically. and mutants display mitochondrial abnormalities,...
Bv8 (prokineticin 2) expressed by Gr1(+)CD11b(+) myeloid cells is critical for VEGF-independent tumor angiogenesis. Although granulocyte colony-stimulating factor (G-CSF) has been shown to be a key inducer of expression, the basis production in driving angiogenesis undefined. Because cell adhesion molecule CEACAM1, which highly on cells, known regulate G-CSF receptor (G-CSFR) signaling, we hypothesized that CEACAM1 would these cells. In support this hypothesis, found expression was elevated...
Glioblastoma (GBM) is the most common malignant brain cancer. Increasing evidence suggests that mitochondrial dysfunction plays a key role in GBM progression as mitochondria essential regulating cell metabolism, oxidative stress, and death. Meanwhile, immune microenvironment predominated by tumor-associated macrophages microglia (TAM), which heterogenous population of myeloid cells that, general, create an immunosuppressive milieu to support tumor growth. However, subsets TAMs can be...
Immune oncology (IO) is challenged to expand its usefulness a broader range of cancers. A second generation IO agents acting beyond the realm Checkpoint Inhibitor Therapy (CIT) sought with intent turning immune-resistant cancers into appealing targets. The published literature proposes profusion models explain cancer immune resistance CIT that largely outnumber landscapes and corresponding mechanisms. In spite complex contradicting suggested refractoriness CIT, identification prevailing...
The rapid and sustained proliferation in cancer cells requires accelerated protein synthesis. Accelerated synthesis disordered cell metabolism greatly increase the risk of translation errors. ribosome-associated quality control (RQC) is a recently discovered mechanism for resolving ribosome collisions caused by frequent stalls. role RQC pathway initiation progression remains controversial confusing. In this study, we investigated pathogenic mitochondrial stress-induced carboxyl-terminal...
Abstract The rapid and sustained proliferation in cancer cells requires accelerated protein synthesis. Accelerated synthesis disordered cell metabolism greatly increase the risk of translation errors. ribosome-associated quality control (RQC) is a recently discovered mechanism for resolving ribosome collisions caused by frequent stalls. role RQC pathway initiation progression remains controversial confusing. In this study, we investigated pathogenic mitochondrial stress-induced...
Following publication of the original article [1], author reported that an name, Roberta Zappasodi, was missed in authorship list. Davide Bedognetti, Rongze Lu, Josue Samayoa, Stefani Spranger and Sarah Warren contributed equally to this work. The can be found online at 10.1186/s40425-019-0602-4
The rapid and sustained proliferation in cancer cells requires accelerated protein synthesis. Accelerated synthesis disordered cell metabolism greatly increase the risk of translation errors. ribosome-associated quality control (RQC) is a recently discovered mechanism for resolving ribosome collisions caused by frequent stalls. role RQC pathway initiation progression remains controversial confusing. In this study, we investigated pathogenic mitochondrial stress-induced carboxyl-terminal...