Publications by authors named "Avni Awani"
Objective: X-linked adrenoleukodystrophy (ALD) is caused by mutations in ABCD1, a peroxisomal gene. More than half of males with an ABCD1 mutation develop inflammatory cerebral demyelination (cALD), but underlying mechanisms remain unknown and therapies are limited. We sought to develop and characterize a mouse model of cALD to facilitate study of disease mechanisms and therapy development.
View Article and Find Full Text PDFArticle 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.
Objective: We sought to create and characterize a mouse model of the inflammatory, cerebral demyelinating phenotype of X-linked adrenoleukodystrophy (ALD) that would facilitate the study of disease pathogenesis and therapy development. We also sought to cross-validate potential therapeutic targets such as fibrin, oxidative stress, and the NLRP3 inflammasome, in post-mortem human and murine brain tissues.
Background: ALD is caused by mutations in the gene encoding a peroxisomal transporter.
Background And Objectives: There are no therapies for preventing cerebral demyelination in X-linked adrenoleukodystrophy (ALD). Higher plasma vitamin D levels have been linked to lower risk of inflammatory brain lesions. We assessed the safety and pharmacokinetics of oral vitamin D dosing regimens in boys and young men with ALD.
View Article and Find Full Text PDFVitamin D is a steroid hormone that has been widely studied as a potential therapy for multiple sclerosis and other inflammatory disorders. Pre-clinical studies have implicated vitamin D in the transcription of thousands of genes, but its influence may vary by cell type. A handful of clinical studies have failed to identify an in vivo gene expression signature when using bulk analysis of all peripheral immune cells.
View Article and Find Full Text PDF