Qingde Wang, MD, PhD*
3459 Fifth Avenue
Pittsburgh, PA 15213
RNA is an essential molecule for all biological activities, especially the function of liver in which the most complexed biochemical reaction occurs catalyzed by a large number of protein enzymes. RNA only carries out but also regulates the gene expression, and thus involves in many critical biologic and pathologic processes. For proper function of RNA, it needs post-transcriptional process which converts the pre-RNAs to functional mature RNAs. Our research interest is to delineate how RNA is process by the RNA editing proteins and how it plays its roles in diseases. Particularly our studies focus on a RNA editing enzyme ADAR1, which plays its most critical role in liver. Through generation of variant genetically modified animal models, we demonstrated that ADAR1 plays critical role in liver development, liver inflammatory injury, non-alcoholic fatty liver disease, as well as hepatocellular carcinoma. We carry out studies to gain insight in the molecular mechanisms of the related diseases and develop potential approaches to interrupt or reverse the pathologic progress and treat the patients.
- Role of RNA editing enzyme ADAR1 in NAFLD and NASH. NAFLD is the most common chronic liver disease and may eventually develop to end stage cirrhosis and hepatocellular carcinoma. Inflammation is a key pathologic change that determines the prognosis; however how the inflammation is triggered is yet to be fully understood. We found that improperly processed cellular RNA in metabolically stressed hepatocytes may trigger the inflammation. This project is carried out through collaboration with Dr. Paul Monga to elucidate the detailed mechanism.
- Innate immune responses in liver sterile inflammatory injuries. We are the first found that RNA editing enzyme ADAR1 suppresses the cytosolic RNA sensing pathway of the innate immune responding to endogenous RNA, deficiency of ADAR1 involves in variant liver pathogenesis of inflammatory injuries, including trauma, ischemia/reperfusion and autoimmune diseases. We are testing whether interrupting this ADAR1-RNA editing-RNA sensing signaling pathway can be developed to a potential therapeutic approach for treating liver inflammatory diseases.
- Molecular basis of RNA editing in hepatocyte. Data from our knockout mouse models showed that deletion of ADAR1 preferentially interrupts liver’s integrity and functions. Embryonic liver development can be severely interrupted in the ADAR1 deficient mouse, and ADAR1 deficiency also shifts the gene transcription profile in adult hepatocytes. Through a yet to be found mechanism ADAR1 regulates the liver development and hepatocyte maturation. We are working to find the molecular mechanism how ADAR1 execute its function in hepatocytes.
Department of Surgery