Combinatorial signals regulating liver differentiation
The bipotential differentiation of liver progenitor cells is integral to liver development, regeneration, and diseases including bile duct paucity and liver cancer. The regionalization of biliary differentiation and morphogenesis near the portal region of the liver has suggested that spatially segregated microenvironmental signals govern this process. Accordingly, both TGF beta and Notch signaling have been demonstrated to be activated in the portal area, and both have been shown to be critical mediators of bile duct formation. We have recently developed a cell microarray platform that enabled the systematic analysis of liver progenitor fate specification within defined microenvironments, and in particular, facilitated the assessment of interactions between TGF beta, Notch, and other microenvironmental cues including extracellular matrix. Our data further suggest that mechanical signals may play role in liver progenitor function, and that spatial patterns of cell mechanotransduction cooperate with Notch and other signals to regulate differentiation fate.
Bio
Gregory H. Underhill is an Assistant Professor of Bioengineering at the University of Illinois at Urbana-Champaign. Dr. Underhill received his PhD from Northwestern University, with his doctoral research focused on the mechanisms controlling the recruitment of T lymphocytes and the functional characteristics of antibody secreting plasma cells. Dr. Underhill also completed a postdoctoral fellowship in Dr. Sangeeta Bhatia’s laboratory at MIT, where he worked to develop and apply engineered cell culture platforms towards the study of cell functions. His current research is focused on studying cellular fate decisions, including the tissue development and engineering of the liver. These efforts are at the interface of cell and developmental biology, genomics, biomaterials, and microfabrication. Dr. Underhill was a Ruth L. Kirschstein postdoctoral fellow.