Diya Patel
Research Mentor: Sunny Kataria
Mentor Department: Not Available, Not Available
Author(s): Not Available
Session: Session 5 (2:00 PM – 2:50 PM)
Presentation Type: Poster 42
Abstract
Fibrosis is characterized by excessive deposition of extracellular matrix (ECM) proteins that leads to tissue stiffening, organ dysfunction, and eventual failure. In systemic sclerosis (scleroderma), progressive fibrosis of the skin and internal organs, particularly the lungs, is a major cause of morbidity and mortality. Current therapies primarily slow disease progression but do not reverse established fibrotic remodeling. This highlights the need for treatments that directly target the mechanisms driving fibrosis. Fibroblasts are the primary ECM-producing cells in this process, and persistent activation of fibroblasts promotes their differentiation into myofibroblasts that produce large amounts of collagen. Recent studies have identified the histone acetyltransferase and transcriptional coactivator p300 (EP300) as a key epigenetic regulator of profibrotic gene expression. Elevated EP300 activity promotes fibroblast activation and sustained ECM production in fibrotic diseases. Proteolysis targeting chimeras (PROTACs) are a class of small molecules that induce selective degradation of target proteins through the ubiquitin–proteasome system. Unlike traditional inhibitors, PROTACs remove the target protein entirely, allowing disruption of both catalytic and non catalytic functions. In this project, we investigate the therapeutic potential of the PROTAC CBPD-409 to degrade p300 in scleroderma dermal and lung fibroblasts. We evaluate whether targeted degradation of p300 can reduce fibroblast activation and fibrotic gene expression. These findings may help establish p300 degradation as a potential therapeutic strategy for reversing fibrosis in systemic sclerosis.
