Publications by authors named "Sean P Harrison"
Article Synopsis
- * Key findings reveal that expression of aquaporins (AQP8 and AQP9) increases during cell differentiation, but AQP8 protein levels decrease post-hypoxia despite increased mRNA levels after reoxygenation.
- * The research indicates that post-transcriptional mechanisms, rather than transcription changes, lead to reduced AQP8 protein concentration after hypoxia and reoxygenation events in liver cells.
Article Synopsis
- The study focuses on using parenteral nutrition (PN) for premature newborns, who are at risk for liver disease associated with PN, and aims to develop predictive models for this condition.
- Researchers utilized liver organoids derived from induced pluripotent stem cells to simulate the liver environment and assess the effects of different lipid treatments used in PN.
- Results indicated that both lipid treatments led to lipid accumulation in liver cells and decreased liver function markers, suggesting that liver organoids could serve as a useful platform for testing new, less harmful PN solutions.
Article Synopsis
- The development of organoid models, especially for the liver, addresses the limitations of traditional 2D cell culture by creating more physiologically relevant systems that better mimic native tissue.
- The new approach eliminates the need for 2D patterning and extracellular matrices, using small molecules to replicate embryonic liver development, resulting in liver-like organoids with complex cellular structures.
- These liver organoids demonstrate critical functions such as drug metabolism and protein production, and can be transplanted into mice, maintaining their functionality and offering potential for applications in therapy, drug testing, and disease modeling.
Article Synopsis
- Aagenaes syndrome is an autosomal recessive condition that includes symptoms like neonatal cholestasis, lymphedema, and giant cell hepatitis, with its genetic cause previously unknown.
- Researchers studied 26 patients and their parents using techniques like whole-genome sequencing and CRISPR to pinpoint genetic variants affecting the disease.
- The study identified a specific variant (c.-98G>T) in the UNC45A gene present in all patients, indicating it as the genetic cause of Aagenaes syndrome, and showed reduced expression of the UNC45A protein in affected individuals.
Article Synopsis
- - The bleeding problems in hereditary coagulation disorders stem from low or absent activity of hemostasis proteins due to genetic changes, with most of these factors produced in the liver.
- - Current models using human or animal cells fail to accurately replicate the liver's biology and the specific genetic background of patients, limiting research on these disorders.
- - Induced Pluripotent Stem Cell (iPSC) technology, combined with CRISPR/Cas9, allows for the creation of patient-specific liver organoids, providing a more accurate platform for studying coagulation proteins and developing potential therapies for these inherited disorders.
Article Synopsis
- Induced pluripotent stem cells (iPSCs) can be differentiated into various liver cell types, providing a unique opportunity to study liver development, toxicity, and diseases with patient-specific contexts, overcoming limitations imposed by the availability of primary tissues.
- Current research focuses on 3D or organotypic differentiation of iPSCs, creating more realistic models that mimic liver tissue architecture and cell interactions, which could potentially replace animal models in clinical settings.
- A variety of liver organoid models exist, from simple single-cell structures to complex systems that include multiple cell types, enhancing functionality for drug metabolism and disease studies; however, more advanced organotypic models are needed for better disease modeling and therapeutic development.