Cardiac fibrosis—the stiffening and scarring of heart tissue—contributes to nearly every form of heart disease yet has long eluded effective treatment. The study reveals that matrix stiffness itself drives ongoing fibroblast activation, sustaining fibrotic remodeling even after inflammatory signals diminish. By identifying SRC, a focal adhesion-associated tyrosine kinase, as a critical mechanosensor highly active in cardiac fibroblasts, the researchers demonstrate a new therapeutic opportunity.
In collaboration with Greenstone Biosciences, the team conducted an AI-driven virtual screen of over 10,000 compounds. Greenstone’s AI-ML and Computational Biology team, including Dr. Souhrid Mukherjee and Dr. Jeremy Leitz, identified saracatinib—an orphan drug originally developed for cancer—as a potent SRC inhibitor capable of reversing fibrosis.
In vitro and in vivo experiments showed that dual inhibition of SRC and the TGF-β pathway not only suppressed fibroblast activation but also restored healthy tissue function in engineered heart tissues and a preclinical mouse model of heart failure. This combined biochemical and biomechanical targeting approach offers a powerful blueprint for future 'mechanotherapies' to reverse fibrosis, not just slow its progression.
“At Greenstone Biosciences, we are committed to advancing precision therapeutics by integrating iPSC technology with AI-powered discovery,” said the leadership team in a joint statement. “We are honored to contribute to research that redefines what is possible for millions of patients suffering from fibrotic diseases.”
This
work was supported by grants from the National Institutes of Health and a
Stanford Cardiovascular Institute seed award. Additional Stanford-affiliated
investigators included Virginia Winn, Y. Joseph Woo, and Helen Blau.
For additional details on the study,
see the Stanford Cardiovascular Institute release: https://med.stanford.edu/cvi/mission/news_center/articles_announcements/2025/new-approach-to-treating-cardiac-fibrosis.html
About
Greenstone Biosciences
Based in Palo Alto, California, Greenstone Biosciences applies cutting-edge
clinical genomics, computational biology, and patient-specific iPSC technology
to decode pharmacogenomic variation and accelerate drug discovery. Leveraging
the world’s largest repository of patient-derived iPSC lines across diverse
diseases and ethnic backgrounds, Greenstone delivers unrivaled insights into
human biology. The company collaborates with leading academic partners
worldwide to advance the development of precision medicines. Learn more at www.greenstonebio.com.