A5027663427- Drug Transport and Resistance Mechanisms
- Cell Adhesion Molecules Research
- MicroRNA in disease regulation
- Barrier Structure and Function Studies
- Cellular Mechanics and Interactions
- Glioma Diagnosis and Treatment
- Neonatal and fetal brain pathology
- Single-cell and spatial transcriptomics
- Protein Degradation and Inhibitors
- HER2/EGFR in Cancer Research
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- Zebrafish Biomedical Research Applications
- Proteoglycans and glycosaminoglycans research
- RNA Interference and Gene Delivery
- Cellular transport and secretion
- Trace Elements in Health
- Platelet Disorders and Treatments
- Epigenetics and DNA Methylation
- Hippo pathway signaling and YAP/TAZ
- Renal and related cancers
- Erythrocyte Function and Pathophysiology
- Ocular Oncology and Treatments
National Cancer Institute
2019-2025
National Institutes of Health
2019-2025
Center for Cancer Research
2019-2025
University of Liverpool
2018-2019
Abstract Background A principal protective component of the mammalian blood–brain barrier (BBB) is high expression multidrug efflux transporters P-glycoprotein (P-gp, encoded by ABCB1 ) and ABCG2 (encoded on lumenal surface endothelial cells. The zebrafish P-gp homolog Abcb4 expressed at BBB phenocopies human P-gp. Comparatively little known about four homologs gene: abcg2a , abcg2b abcg2c abcg2d . Here we report functional characterization brain tissue distribution homologs. Methods To...
The brain is protected from toxins by a tightly regulated network of specialized cells, including endothelial pericytes, astrocyes, and neurons, known collectively as the blood-brain barrier (BBB). This selectively permeable permits only most crucial molecules essential for function to enter employs number different mechanisms prevent entry potentially harmful pathogens. In addition physical comprised cells that form tight junctions restrict paracellular transport, there an active protective...
Purpose: Over 90% of uveal melanomas harbor pathogenic variants the GNAQ or GNA11 genes that activate survival pathways. As previous studies found Ras-mutated cell lines were vulnerable to a combination pathway inhibitors and histone-deacetylase inhibitor romidepsin, we investigated whether this would be effective in models melanoma. Methods: A small-scale screen bromodomain-containing protein 4 (BRD4; OTX-015), extracellular signal-related kinase (ERK; ulixertinib), mechanistic target...
Abstract Background A principal protective component of the mammalian blood-brain barrier (BBB) is high expression multidrug efflux transporters P-glycoprotein (P-gp, encoded by ABCB1 ) and ABCG2 (encoded on lumenal surface endothelial cells. The zebrafish P-gp homolog Abcb4 expressed at BBB phenocopies human P-gp. Comparatively little known about four homologs gene: abcg2a , abcg2b abcg2c abcg2d . Here we report functional characterization brain tissue distribution homologs. Methods To...
Abstract Crosstalk between adhesion and growth factor receptors plays a critical role in tissue morphogenesis repair, aberrations contribute substantially to neoplastic disease. However, the mechanisms by which receptor signalling are integrated, spatially temporally, unclear. We used complex enrichment coupled with quantitative proteomic analysis identify rapid changes composition following stimulation. Bioinformatic network ontological analyses revealed substantial decrease abundance of...
ATP-binding cassette (ABC) transporters expressed at the blood-brain barrier (BBB) impede delivery of therapeutic agents to brain, including treat neurodegenerative diseases and primary metastatic brain cancers. Two transporters, ABCB1 ABCG2, are highly BBB responsible for efflux numerous clinically useful chemotherapeutic agents, irinotecan, paclitaxel, doxorubicin. Based on a previous mouse model, we have generated transgenic zebrafish in which expression NanoLuciferase (NanoLuc) is...
Abstract The mechanical properties of the extracellular matrix within tumours control multiple cellular functions that drive cancer invasion and metastasis. However, mechanisms controlling microenvironmental force sensation transmission, how these regulate transcriptional reprogramming invasion, are unclear. Our aim was to understand inputs transmitted bidirectionally translated into biochemical outputs breast progression. We reveal adhesion receptor growth factor crosstalk regulates a...
Abstract ATP-binding cassette (ABC) transporters expressed at the blood-brain barrier (BBB) impede delivery of therapeutic agents to brain, including treat neurodegenerative diseases and primary metastatic brain cancers. Two transporters, P-glycoprotein (P-gp, ABCB1) ABCG2, are highly BBB responsible for efflux numerous clinically useful chemotherapeutic agents, irinotecan, paclitaxel, doxorubicin. Based on a previous mouse model, we have generated transgenic zebrafish in which expression...