Description of Research Expertise

Dr. Raabe is a Research Assistant Professor at the Division of Translational Medicine and Human Genetics at the Department of Medicine. His lab is pioneering the derivation and characterization of adult mouse and human liver derived bipotent ductal organoids. These organoids can be cloned and passaged over many months in culture but their genetic manipulation is challenging. The Raabe lab uses these organoids for liver cell/gene therapy as well as for liver disease modeling and drug screening. Recently, the Raabe lab discovered that bipotent ductal organoids can readily be derived from endstage MASH patient liver and have shown that they share many functional properties of the MASH liver they were derived from. This opens a new area of personalized functional analysis and medicine for MASH based on MASH patient liver derived organoids. In addition, the Raabe lab has strong expertise in CRISPR-mediated gene targeting, originally by generation many novel CRISPR mediated mutant mice. Most recently, he works on CRISPR - generated knockout and knockin models in human tissue derived organoids which are traditionally hard to genetically manipulate. To address this, Dr. Raabe has initiated in 2023 a collaboration with the Weissmann and Muzykantov labs at the Penn Institute for RNA Innovation to use mRNA LNPs for fast and efficient gene targeting directly in non proliferating MASH organoid co-cultures. These co-cultures consist of parenchymal cells as well as other profibrotic cell types such as myofibrolasts and macrophages. LNPs targeting specifically each cell type have been generated successfully. They are currently employed to probe specific profibrotic pathways in these cell types in the context of multi cell type co-cultures. Importantly this LNP-organoid system allows for high throughput screening applications to discover new gene specific LNP mediated candidate therapeutic treatments.