Mirian Fernández-Vaquero
A5007585092- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer-related gene regulation
- RNA modifications and cancer
- Peptidase Inhibition and Analysis
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Liver Disease Diagnosis and Treatment
- Liver physiology and pathology
- Diabetes and associated disorders
- Circular RNAs in diseases
- Immunotherapy and Immune Responses
- Liver Diseases and Immunity
- Pancreatitis Pathology and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Barrier Structure and Function Studies
- Immune Cell Function and Interaction
- Ferroptosis and cancer prognosis
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- RNA regulation and disease
- CAR-T cell therapy research
- Cancer, Hypoxia, and Metabolism
German Cancer Research Center
2021-2025
Heidelberg University
2021-2024
The progression of non-alcoholic steatohepatitis (NASH) to fibrosis and hepatocellular carcinoma (HCC) is aggravated by auto-aggressive T cells. gut-liver axis contributes NASH, but the mechanisms involved consequences for NASH-induced liver cancer remain unknown. We investigated role gastrointestinal B cells in development HCC.
Abstract Dendritic cells (DCs) are antigen-presenting myeloid that regulate T cell activation, trafficking and function. Monocyte-derived DCs pulsed with tumor antigens have been tested extensively for therapeutic vaccination in cancer, mixed clinical results. Here, we present a cell-therapy platform based on mouse or human DC progenitors (DCPs) engineered to produce two immunostimulatory cytokines, IL-12 FLT3L. Cytokine-armed DCPs differentiated into conventional type-I (cDC1) suppressed...
Abstract Isocitrate dehydrogenase 1 mutations (mIDH1) are common in cholangiocarcinoma. (R)-2-hydroxyglutarate generated by the mIDH1 enzyme inhibits multiple α-ketoglutarate–dependent enzymes, altering epigenetics and metabolism. Here, developing mIDH1-driven genetically engineered mouse models, we show that supports cholangiocarcinoma tumor maintenance through an immunoevasion program centered on dual (R)-2-hydroxyglutarate–mediated mechanisms: suppression of CD8+ T-cell activity...
Abstract Chronic liver disease and hepatocellular carcinoma (HCC) are life-threatening diseases with limited treatment options. The lack of clinically relevant/tractable experimental models hampers therapeutic discovery. Here, we develop a simple robust human cell-based system modeling clinical prognostic signature (PLS) predicting long-term progression toward HCC. Using the PLS as readout, followed by validation in nonalcoholic steatohepatitis/fibrosis/HCC animal patient-derived spheroids,...
Abstract Background RNA editing has been described as promoting genetic heterogeneity, leading to the development of multiple disorders, including cancer. The cytosine deaminase APOBEC3B is implicated in tumor evolution through DNA mutation, but whether it also functions an enzyme not studied. Results Here, we engineer a novel doxycycline-inducible mouse model human APOBEC3B-overexpression understand impact this tissue homeostasis and address potential role C-to-U editing. Elevated sustained...
Abstract Introduction: Cholangiocarcinoma (CCA) is a highly aggressive adenocarcinoma of the hepatobiliary system showing an alarming rise in incidence and mortality with unsatisfactory treatment options. Claudin-1 (CLDN1) transmembrane protein expressed tight junctions, but exposed at cell surface on cancer epithelial cells. Using specific monoclonal antibodies (mAbs) targeting extracellular loop 1 CLDN1 excellent safety profile (Roehlen, Saviano et al. Science Transl Med 2022), we aimed to...
Supplementary Figure from Mutant IDH Inhibits IFNγ–TET2 Signaling to Promote Immunoevasion and Tumor Maintenance in Cholangiocarcinoma
<div>Abstract<p>Isocitrate dehydrogenase 1 mutations (mIDH1) are common in cholangiocarcinoma. (R)-2-hydroxyglutarate generated by the mIDH1 enzyme inhibits multiple α-ketoglutarate–dependent enzymes, altering epigenetics and metabolism. Here, developing mIDH1-driven genetically engineered mouse models, we show that supports cholangiocarcinoma tumor maintenance through an immunoevasion program centered on dual (R)-2-hydroxyglutarate–mediated mechanisms: suppression of...
<div>Abstract<p>Isocitrate dehydrogenase 1 mutations (mIDH1) are common in cholangiocarcinoma. (R)-2-hydroxyglutarate generated by the mIDH1 enzyme inhibits multiple α-ketoglutarate–dependent enzymes, altering epigenetics and metabolism. Here, developing mIDH1-driven genetically engineered mouse models, we show that supports cholangiocarcinoma tumor maintenance through an immunoevasion program centered on dual (R)-2-hydroxyglutarate–mediated mechanisms: suppression of...
Supplementary Figure from Mutant IDH Inhibits IFNγ–TET2 Signaling to Promote Immunoevasion and Tumor Maintenance in Cholangiocarcinoma
Abstract Intrahepatic cholangiocarcinoma (iCCA) primarily arises from the transformation of cholangiocytes (epithelial cells bile ducts), is diagnosed at late stage and has a dismal prognosis (average 5-year survival after resection 32%). An alarming increase in its incidence over past decades scarce treatment options available urges for development novel therapeutic strategies to tackle this malignancy. Immunotherapy had limited success iCCA. Possible explanations are that iCCA immune...