Victoria Stefanelli

Ph.D. Proposal Presentation

Thursday, September 24th 2015, 3 p.m.

EBB 1005

Advisor: Thomas Barker, Ph.D. (Georgia Institute of Technology, BME)

Committee:

Melissa Kemp, Ph.D. (Georgia Institute of Technology, BME)

Johnna Temenoff, Ph.D. (Georgia Institute of Technology, BME)

Matthew Torres, Ph.D. (Georgia Institute of Technology, Biology)

Eric White, MD. (University of Michigan)

“Provisional Matrix Citrullination as an Activator of Fibroblasts in Idiopathic Pulmonary Fibrosis”

Abstract: 

Idiopathic pulmonary fibrosis (IPF) is a condition involving progressive scarring of the lungs with a mean survival rate of three years after diagnosis, for which there is currently no effective preventative or curative therapy.  Substantial evidence has identified activated lung fibroblasts—characterized by invasiveness, apoptotic resistance, and excessive secretion of extracellular matrix (ECM) proteins—as the main drivers of IPF, although mechanisms behind initiation and persistence of altered fibroblast phenotypes are not well understood. This research will explore a novel mechanism for fibroblast activation: citrullination of the provisional lung ECM.  Citrullination is a post-translational protein modification associated with inflammation and known to occur extensively in early stages of lung disease. Its role in the progression of IPF will be investigated through an analysis of integrin-mediated interactions relevant to cell adhesion, migration, and contraction, in addition to its influence of intracellular signaling pertinent to myofibroblast differentiation and apoptosis.  Further, the clinical implications of citrullination as a therapeutic target will be examined in a murine model of lung fibrosis.  This research is significant for expanding scientific understanding of the fundamental role citrullinated ECM plays in the development and progression of many chronic inflammatory conditions, also including rheumatoid arthritis, multiple sclerosis, and cancer.