William Brodie
Pronouns: He/Him
Research Mentor(s): Eliza Tsou
Co-Presenter: Mattichak, Megan
Research Mentor School/College/Department: Internal Medicine / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 5 – 3:40pm – 4:30 pm
Room: League Ballroom
Authors: William Brodie, Megan Mattichak, Sirapa Vichaikul, Mikel Gurrea-Rubio, M. Asif Amin, Phillip Campbell, Qi Wu, Dinesh Khanna, Eliza Tsou
Presenter: 59
Abstract
Binding of the bromodomain and extra-terminal domain proteins (BETs) to acetylated histone residues is critical for gene transcription. This study sought to determine the anti-fibrotic efficacy and potential mechanisms of BET inhibition in systemic sclerosis (SSc), specifically focusing on the bromodomain-containing protein 4 (BRD4) isoform. BRD4 blockade showed anti-fibrotic effects in an animal model of SSc and in patient-derived diffuse cutaneous SSc fibroblasts. The anti-fibrotic effect of BRD4 inhibition was at least in part mediated by downregulation of Ca2+/calmodulin-dependent protein kinase II a (CaMKII-a) and reducing intracellular calcium concentrations. These results suggest that targeting calcium pathways or BRD4 might be novel therapeutic approach for progressive tissue fibrosis.
Biomedical Sciences, Natural/Life Sciences
