Dr. Huebert's Biliary Regenerative Medicine Laboratory has four major parallel lines of investigation:
Molecular mechanisms of cholestatic fibrogenesis
Biliary fibrosis is the process of periportal scarring within the liver that is caused by diseased bile ducts and often progresses to end-stage liver disease. Currently, liver transplantation is the only effective treatment for end-stage liver disease. However, due to a severe shortage of donor organs, many patients die awaiting liver transplantation. Thus, it is necessary to understand the mechanisms regulating biliary fibrosis and to identify pathways that can be targeted therapeutically. This project focuses on understanding how epigenetic dysregulation in cholangiocytes leads to the release of paracrine molecules that subsequently activate myofibroblasts. In particular, the project will identify the specific signaling events and epigenetic complexes that drive fibrogenic gene expression in cholangiocytes. These efforts are designed to identify new molecular targets that can be regulated to more effectively treat patients.
Cholangiocytes derived from iPSCs
Dr. Huebert's laboratory pioneered a novel technology to create cholangiocytes from induced pluripotent stem cells (iPSCs). This technology not only allows the laboratory to test the genetic and epigenetic mechanisms underlying biliary development and pathophysiology, but also is a platform for individualized modeling of biliary disease and testing pharmacotherapies.
In conjunction with the Mayo Clinic Regenerative Medicine Biotrust, Dr. Huebert has created a biorepository of iPSCs from patients with liver disease. This robust biorepository serves as a powerful source of patient-specific cells to enhance the study and treatment of liver disease.
Decellularized and recellularized liver
Dr. Huebert's lab is collaborating with Scott L. Nyberg, M.D., Ph.D.; Allan B. Dietz, Ph.D.; and an industry partner (Miromatrix) to generate tissue-engineered liver grafts as a potential solution to the shortage of donor livers for solid organ liver transplantation. These studies offer the potential to create unlimited organs for liver transplantation.
The long-term goals of the laboratory include development of epigenetic pharmacology and regenerative therapeutics for biliary disease.