Laufer, CraigBeyer, RachelBoyd, AnnBreehl, Nicholas2021-04-272021-04-272021-04-26http://hdl.handle.net/11603/21392This project is aimed to investigate micro-RNA as a potential therapeutic approach for silencing ubiquitin-associated and SH3-domain-containing A (UBASH3A), a negative regulator of the NF-kB pathway in CD4+ T cell Receptor and CD-28 signaling. UBASH3A expression is upregulated in patients of Type-1 Diabetes (T1D) who harbor risk alleles RS11203203 and RS80054410 on chromosome 21 resulting in single nucleotide polymorphisms. Increases in UBASH3A decrease IL-2 and therefore T1Ds experience pathogenesis via lack of T regulatory (T reg/T-reg) cell development from the loss of the pleiotropic cytokine. It has previously been shown, using clustered regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated protein 9 (Cas-9) edited CD4+ T cells, that the silencing of UBASH3A results in a decrease in the protein and an increase of IL-2 production. This study will determine if the use of micro-RNA directed towards the UBASH3A messenger RNA can reduce UBASH3A protein and rescue IL-2 production in T cells. This work will pave the way for future studies that aim to treat patients with T1D.en-USCC0 1.0 Universalhttp://creativecommons.org/publicdomain/zero/1.0/UBASH3Adiabetesdiabetes mellitustype-1 diabetesautoimmuneT-cellNF-kBText