A5002480833- Immunotherapy and Immune Responses
- DNA and Nucleic Acid Chemistry
- Genomics and Chromatin Dynamics
- vaccines and immunoinformatics approaches
- DNA Repair Mechanisms
- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- Planarian Biology and Electrostimulation
- interferon and immune responses
- Cellular transport and secretion
- Pancreatic function and diabetes
- Liver Disease Diagnosis and Treatment
- Liver physiology and pathology
- Epigenetics and DNA Methylation
- Inflammasome and immune disorders
- Lysosomal Storage Disorders Research
- Carbohydrate Chemistry and Synthesis
- Renal and related cancers
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
Princess Máxima Center
2023-2024
Leiden University Medical Center
2019-2020
Leiden University
2019
Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date, solely established pluripotent stem cells. Here, we show that healthy human fetal in vitro self-organizes into (FeBOs), phenocopying aspects of vivo cellular heterogeneity and complex organization. FeBOs expanded over long time periods. FeBO growth...
Abstract Pluripotent stem cell (PSC)-derived human brain organoids enable the study of development in vitro. Typically, fate PSCs is guided into subsequent specification steps through static medium switches. In vivo, morphogen gradients are critical for proper and determine specification, associated defects result neurodevelopmental disorders. Here, we show that initiating neural induction a temporal stepwise gradient guides generation composed single, self-organized apical-out...
Abstract Mechanisms underlying human hepatocyte growth in development and regeneration are incompletely understood. In vitro, fetal hepatocytes (FH) can be robustly grown as organoids, while adult primary (PHH) organoids remain difficult to expand, suggesting different requirements between hepatocytes. Here, we characterize organoid outgrowth using temporal transcriptomic phenotypic approaches. FHs initiate reciprocal transcriptional programs involving increased proliferation repressed lipid...
Glucocerebrosidase (GBA) is a lysosomal β-glucosidase-degrading glucosylceramide. Its deficiency causes Gaucher disease (GD), common storage disorder. Carrying genetic abnormality in GBA constitutes at present the largest risk factor for Parkinson's (PD). Conduritol B epoxide (CBE), mechanism-based irreversible inhibitor of GBA, used to generate cell and animal models investigations on GD PD. However, CBE may have additional glycosidase targets besides GBA. Here, we first vivo target...
Pyroptosis is a recently discovered form of inflammatory programmed necrosis characterized by caspase-1-mediated and gasdermin D-dependent cell death leading to the release pro-inflammatory cytokines such as Interleukin-1 beta (IL-1β). Here, we evaluated whether pyroptosis could be exploited in DNA vaccination incorporating constitutively active variant caspase-1 antigen-expressing DNA. In vitro, transfection with induced pro-IL-1β maturation IL-1β well death. To test genetic adjuvant for...
CD4
Abstract Transcription-coupled repair (TCR) removes DNA lesions from the transcribed strand of active genes. Stalling RNA polymerase II (RNAPII) at initiates TCR through recruitment CSB and CSA proteins. The full repertoire proteins required for human – particularly in a chromatin context - remains to be determined. Studies mice have revealed that nucleosome-binding protein HMGN1 is enhance UV-induced However, whether unaddressed. Here, we show knockout or knockdown HMGN1, either alone...
Summary Transcription-coupled repair (TCR) removes DNA lesions from the transcribed strand of active genes. Stalling RNA polymerase II (RNAPII) at initiates TCR through recruitment CSB and CSA proteins. The full repertoire proteins required for human – particularly in a chromatin context - remains to be determined. Studies mice have revealed that nucleosome-binding protein HMGN1 is enhance UV-induced However, whether unaddressed. Here, we show knockout or knockdown HMGN1, either alone...
<h3>Background</h3> As every tumor carries its unique set of neoantigens distinguishing it from healthy tissue, cancer vaccines need to be produced quickly and on an individual basis swiftly induce a broad immune response targeting multiple antigens. DNA provides ideal platform achieve this, as single polyepitope vaccine can encode (>20) However, standard plasmid take months produce tend poorly immunogenic in humans. <h3>Methods</h3> To address the first issue, GMP-compatible method...