Grant: Proof of Principle Program - Phase I

Wound healing is a normal response to tissue injury and involves many growth factors that control cell growth, movement (migration) and production of the extracellular matrix (ECM) that provides structural support to the repairing tissue. Transforming growth factor beta (TGF-beta) is an important factor that controls the normal wound healing response but abnormally high levels of TGF-beta can produce excessive ECM production leading to impaired wound healing, abnormal scarring and fibrotic disorders. Our research focuses on the identification and characterization of naturally produced proteins that block the action of TGF-beta in the skin. We have identified a protein named CD109 that binds to TGF-beta and neutralizes its activity suggesting that it may have therapeutic benefit for the treatment of conditions where excessive TGF-beta levels are involved. CD109 is a relatively large protein (180 kilodaltons or 180 kDa) and so its use as a therapeutic agent might be limited because of an inability to access the disease site. Our goal is to determine the minimum portion of the CD109 protein that binds TGF-beta and use that information to develop smaller CD109 fragments (peptides) that will be more practical for clinical use. Such peptides may also have therapeutic benefits for other human diseases such as cancer.