Publications by authors named "M H Porteus"
Blood transfusion plays a vital role in modern medicine, but frequent shortages occur. Ex vivo manufacturing of red blood cells (RBCs) from universal donor cells offers a potential solution, yet the high cost of recombinant cytokines remains a barrier. Erythropoietin (EPO) signaling is crucial for RBC development, and EPO is among the most expensive media components.
View Article and Find Full Text PDFThe most severe form of α-thalassemia results from loss of all four copies of α-globin. Postnatally, patients face challenges similar to β-thalassemia, including severe anemia and erythrotoxicity due to the imbalance of β-globin and α-globin chains. Despite progress in genome editing treatments for β-thalassemia, there is no analogous curative option for α-thalassemia.
View Article and Find Full Text PDFCD8 T cell exhaustion hampers control of cancer and chronic infections and limits chimeric antigen receptor (CAR) T cell efficacy. Targeting in CAR T cells provides therapeutic benefit; however, TET2's role in exhausted T cell (T) development is unclear. In chronic lymphocytic choriomeningitis virus (LCMV) infection, TET2 drove conversion from stem cell-like T progenitors toward terminally differentiated and effector (T)-like T.
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- Abnormal thalamocortical communication can result in neuropsychiatric disorders, with specific genetic variants in the CACNA1G gene linked to conditions like absence seizures, intellectual disability, and schizophrenia.
- Researchers created a human assembloid model to study the effects of CACNA1G variants on thalamocortical pathways, discovering that a specific variant (M1531V) altered calcium currents in thalamic neurons and increased activity in both thalamic and cortical neurons.
- Conversely, the loss of CACNA1G was found to disrupt thalamocortical connectivity, leading to heightened spontaneous activity in thalamic neurons and abnormal axon projections, highlighting the importance of multi-cellular models in understanding
Article Synopsis
- The study investigates how cellular metabolism changes during hematopoiesis, focusing on the effects of mitochondrial adenylate kinase 2 (AK2) deficiency in a severe immunodeficiency syndrome called reticular dysgenesis.
- Using patient samples and CRISPR-modified human hematopoietic stem cells, the research reveals that AK2 deficiency affects mTOR signaling differently in early versus late granulocyte development, demonstrating the importance of metabolic checkpoints.
- While early-stage AK2-deficient cells maintain survival due to effective metabolic regulation, late-stage cells experience unchecked mTOR activity and energy depletion, leading to proliferation arrest and cell death.