Commitment, Curiosity, and a Generous Spirit Drive Fibrotic Disease Research

Natalie Wilson
June 23, 2022
Carol Feghali-Bostwick
Carol Feghali-Bostwick, Ph.D.

Two things motivate Carol Feghali-Bostwick, Ph.D., Distinguished University Professor and SmartState® and Kitty Trask Holt Endowed Chair for Scleroderma Research, to come to work every day. “I feel a commitment to the patients to keep pushing for an answer and a cure. But I also just love the excitement of research. There’s nothing else I’d rather be doing than getting up and seeing what’s new today,” says Feghali-Bostwick.

She was drawn to fibrotic diseases, in part, because of the wide-ranging applicability of any advances in the field. “Fibrosis can affect any organ in the body,” says Feghali-Bostwick. “It’s the end result of many common diseases–for example, diabetic nephropathy often ends with fibrotic kidney disease. So, anti-fibrotic therapies are likely to have a broad impact and our work has a wide reach.”

Research teams in her lab focus on investigating fibrotic mediators and the mechanisms by which they can cause disease. Specifically, she and her teams develop models of fibrosis to test pro- and anti-fibrotic factors using human skin and lung tissue cultures. “We go beyond in vitro testing in dishes and in vivo studies in mice by testing the efficacy of anti-fibrotic therapies to stop fibrosis and the ability of profibrotic agents to cause fibrosis in human tissues. Because, as we so often discover, things that work in mice are often ineffective in humans,” says Feghali-Bostwick.

The team also investigates epigenetic changes in DNA methylation to better understand why some people develop fibrotic disease while others do not. A recent study of scleroderma in discordant twins–identical sibling pairs in which one developed scleroderma while the other did not–led to significant new findings. “When we compared their epigenetic and gene expression profiles, we could identify novel genes that had never before been reported to be associated with scleroderma,” says Feghali-Bostwick.“ It was an exciting finding because these genes presented new targets for therapy.”

A separate study of anti-fibrotic agents identified a novel enzyme in the glycolic pathway that can cause fibrosis. “We had never before thought that an enzyme involved in glycolysis could cause fibrosis. So, that was also anew finding,” she says.

While these breakthroughs initially led to publications in high-impact journals including the Annals of Rheumatic Diseases and JCI Insight, their impacts reach much further. “The epigenetic and gene expression changes have provided leads for other investigators to follow in their own research,” she says. “The antifibrotic peptide has already been licensed to a company that will take it into human trials and hopefully lead to a new antifibrotic therapy.” This is in addition to a previous, novel small molecule therapy that her research team characterized. In their latest study published in JCI Insight, Feghali-Bostwick’s team found that the E4 peptide reverses fibrosis inhuman and mouse tissues by activating an antifibrotic pathway that is common to all organ systems. The findings are significant because they suggest that the peptide could be effective at reversing fibrosis in multiple organ systems.

Feghali-Bostwick also has a deep commitment to mentorship and serves as director of the MUSC ARROW program (Advancement, Recruitment, and Retention of Women) which aims to support and recruit women in research. “I don’t want everyone else to struggle like I did early in my career. If we can accelerate their advancement and make it easier for the next generation, that would be a good legacy to leave,” she says.

This year, Feghali-Bostwick received a renewal of her NIH K24 award to provide continued support of her passion for mentorship. “I want to help foster the next generation of investigators in scleroderma to ensure a pipeline of junior investigators who are well-trained and have the support they need to be successful,” she says.

Her commitment to research, scientific curiosity, and generosity of spirit, reflect the best qualities we can hope to find in science and medicine and a shining example for those who follow in her footsteps.

Article by Kat Hendrix, Ph.D.