Necessity is the mother of invention for physician-scientists like Darren Yuen, MD, PhD, a nephrologist at St. Michael’s Hospital in Toronto. Frustrated with the lack of treatment options for the progressive scarring in the kidney called fibrosis, he turned to his lab in search of a new anti-fibrotic agent.
His team is among a cohort of researchers who have studied the fibrotic effects of a protein called TGF-β for decades, but so far that work has not yielded new treatments.
“TGF-β hasn’t panned out as a treatment target in kidney patients because it does a lot of things,” Yuen said. That can make it hard to develop treatments that don’t have troublesome side effects. So he decided to pivot his research to look at a protein called YAP that interacts with TGF-β.
Yuen is not alone in turning his attention to YAP. The Yes-associated protein (YAP) is emerging as a key player in kidney health and disease, with findings from multiple research groups converging on YAP as critically important. YAP is part of the Hippo signaling pathway that regulates cell growth and differentiation, with YAP activation linked to several malignancies, said Kirk Campbell, MD, a nephrologist and associate professor of medicine at the Icahn School of Medicine at Mount Sinai in New York.
“We’re sort of at the beginning stages of investigating YAP signaling [in kidney disease],” said Campbell, whose work inspired Yuen to take a look at the protein’s role in fibrosis. We are just scratching the surface.”