Dr. Aronin's laboratory focuses on therapeutics for genetically based disease. We have studied the pathogenesis of CAG trinucleotide repeats disease, especially Huntington’s disease. Results from these studies have wide application to a variety of autosomal dominant diseases. Recent progress emphasizes silencing of the Huntington’s disease mutant gene by gene editing and reduction of mutant huntingtin mRNA and protein by RNA interference. Gene editing and RNAi can be used to silence the mutant huntingtin gene and gene product, while preserving the normal gene. We use adeno-associated virus to deliver CRISPR-Cas9 and small RNAs (microRNAs) to affected cells in the brain. Our work improves understanding the pathogenesis of Huntington’s disease. We work with transgenic and knock-in mice, transgenic sheep and non-human primates to optimize huntingtin lowering strategies. This effort is supported by NIH and philanthropic foundations.
Dr. Mordes and his associates have conducted research on the immunology and immunogenetics of type 1 diabetes in rodent models. This work most recently led to the discovery of novel susceptibly gene, TCRBV13a, T Cell receptor beta chain variable region gene. Deletion of T cells that express Vβ13a protein by gene knockout or pharmacologic deletion prevents the disease. The current goal is to translate this discovery to humans at risk for the disease.