Dr. Huebert's Biliary Regenerative Medicine Laboratory has four major parallel lines of investigation:
Liver progenitor cell activation and differentiation
Dr. Huebert's group studies the molecular mechanisms that coordinate the activation and differentiation of liver progenitor cells toward cholangiocytes, which involve various developmental morphogens and epigenetic modifiers. This line of research will allow better understanding of the pathophysiology of cholangiopathies, identify new molecular targets, and lead to regenerative medicine strategies to study and treat the disorders.
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 regenerative therapeutics for liver disease. Importantly, the group was the first to demonstrate liver engraftment of stem cell-derived cholangiocytes in vivo, setting the stage for cell-based regenerative therapeutic options for the cholangiopathies.