A5011011345- Brain Metastases and Treatment
- Radiopharmaceutical Chemistry and Applications
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Immune cells in cancer
- Cancer-related gene regulation
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Immunotherapy and Immune Responses
- Chemokine receptors and signaling
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- interferon and immune responses
- Viral Infections and Outbreaks Research
- RNA and protein synthesis mechanisms
- Melanoma and MAPK Pathways
- Lung Cancer Research Studies
- Viral Infections and Vectors
- Biochemical and Molecular Research
- Immune Cell Function and Interaction
- Circular RNAs in diseases
University of Chicago
2020-2024
Howard Hughes Medical Institute
2020-2024
-methyladenosine (m
-methyladenosine (m
N6-methyladenosine (m6A) methylation can be deposited on chromatin-associated RNAs (caRNAs) by the RNA methyltransferase complex (MTC) to regulate chromatin state and transcription. However, mechanism which MTC is recruited distinct genomic loci remains elusive. Here we identify RBFOX2, a well-studied RNA-binding protein, as factor that preferentially recognizes m6A caRNAs. RBFOX2 recruit RBM15, an component, facilitate of promoter-associated RNAs. RBM15 also physically interacts with YTHDC1...
Mutation of tet methylcytosine dioxygenase 2 (encoded by TET2) drives myeloid malignancy initiation and progression
The RNA N6-methyladenosine (m6A) methylation is installed by the METTL3-METTL14 methyltransferase complex. This modification has critical regulatory roles in various biological processes. Here, we report that deletion of Mettl14 dramatically reduces mRNA m6A developing B cells and severely blocks cell development mice. Deletion impairs interleukin-7 (IL-7)-induced pro-B proliferation large-pre-B-to-small-pre-B transition causes dramatic abnormalities gene expression programs important for...
Abstract METTL3 and METTL14 are two components that form the core heterodimer of main RNA m6A methyltransferase complex (MTC) installs m6A. Surprisingly, depletion or displayed distinct effects on stemness maintenance mouse embryonic stem cell (mESC). While comparable global hypo-methylation in was observed Mettl3 Mettl14 knockout mESCs, respectively. led to a globally decreased nascent synthesis, whereas resulted transcription upregulation, suggesting might possess an m6A-independent role...
Activation of TGF-β signaling serves as an extrinsic resistance mechanism that limits the potential for radiotherapy. Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) antagonizes is implicated in cancer progression. However, molecular mechanisms BAMBI regulation immune cells its impact on antitumor immunity after radiation have not been established. Here, we show ionizing (IR) specifically reduces expression immunosuppressive myeloid-derived suppressor (MDSCs) both...
RNA N6-methyladenosine (m6A) reader YTHDF1 is implicated in cancer etiology and progression. We discovered that radiotherapy (RT) increased expression dendritic cells (DCs) of PBMCs from patients, but not other immune tested. Elevated DCs was associated with poor outcomes patients receiving RT. found loss Ythdf1 enhanced the antitumor effects ionizing radiation (IR) via increasing cross-priming capacity across multiple murine models. Mechanistically, IR upregulated through STING-IFN-I...
Radiation-mediated immune suppression limits efficacy and is a barrier in cancer therapy. Radiation induces negative regulators of tumor immunity including regulatory T cells (Treg). Mechanisms underlying Treg infiltration after radiotherapy (RT) are poorly defined. Given that conventional dendritic (cDC) maintain Treg, we sought to identify target cDC signaling block radiation.
<div>AbstractPurpose:<p>Radiation-mediated immune suppression limits efficacy and is a barrier in cancer therapy. Radiation induces negative regulators of tumor immunity including regulatory T cells (Treg). Mechanisms underlying Treg infiltration after radiotherapy (RT) are poorly defined. Given that conventional dendritic (cDC) maintain Treg, we sought to identify target cDC signaling block radiation.</p>Experimental Design:<p>Transcriptomics high dimensional flow...
<p>Supplementary Figure S2. Flow cytometric characterization of tumor cDC after local radiation</p>
<p>Supplementary Figure S5. Correlation of a Human DC_Ccl22 Homolog Score and CCL22 expression among multiple TCGA cohorts</p>
<p>Supplementary Figure S7. Characterization of tumor cDC populations in Batf3-/- mice and effect αCCL22 or Treg depletion on the radiation response</p>
<p>Supplementary Figure S3. Changes in MC38 tumor cDC populations after local RT.</p>
<p>Supplementary Figure S10. αEGFR-IFNα enhances radiation efficacy in part through CD8+ T cells</p>
<p>Supplementary Figure S9. Changes in gene expression associated with ISG + cDC2 among sequencing results</p>
<p>Supplementary Figure S1. CCL22-expressing cDC are associated with worse survival in cancer patients</p>
<p>Supplementary Figure S8. Bulk RNA-sequencing of tumor myeloid cells 7 days after RT and αEGFR-IFNα</p>
<p>Supplementary Figure S4. Human expression of FOXP3 with RT and correlation a DC_Ccl22 Homolog Score among TCGA cohorts</p>
<p>Supplementary Figure S6. Treg tumor infiltration after local RT in MC38 tumors and splenic cDC isolation strategy.</p>
Abstract Radiotherapy is an important anticancer treatment modality that activates innate and adaptive immune responses. Local RT induces influx of myeloid cells (mostly myeloid-derived suppressor MDSCs), which suppress T-cell function, in the tumor microenvironment (TME). Alleviating therapy-induced immunosuppression would address a significant barrier to efficacy current cancer immunotherapeutic approaches. When all-trans retinoic acid (RA) was administered with radiation, we observed...