Investigators

Summary

Dr. Monga is the UPMC Endowed Chair for Experimental Pathology at the University of Pittsburgh, School of Medicine. He is a Professor of Pathology and Medicine and the Associate Dean of Research for the School. He is the Executive Vice Chair of Pathology and the Chief of the Division of Experimental and Translational Pathology. He is the inaugural Director of the Pittsburgh Liver Institute and also the founding Director of P30 funded Pittsburgh Liver Research Center (PLRC), which is 1 of the 17 NIDDK-funded Digestive Disease Research Core Centers and only 1 of the 3 with exclusive liver focus. He also runs a T32 funded training program in Regenerative Medicine. He is an academic physician and has focused on elucidating the cellular and molecular underpinnings of liver injury, repair, and liver cancer for more than 22 years and has been consistently funded by NIH and sponsored research agreements from industry throughout his career. He has published 208 articles, received numerous research and mentoring awards and served on boards of both industry and academia. He has made seminal contributions in this area especially in the understanding of the role of complex signaling pathways such as the Wnt, Hippo and others and several of his findings are now on the verge of being translated into patients. 

There are two major research themes within his laboratory. The first focus is in the broad area of liver physiology. This includes the areas of hepatic development, liver regeneration (following surgical resection, drug-induced injury or cholestasis) and metabolic zonation (division of labor within liver lobule). His work has elucidated the cell-molecule circuitry of liver regeneration following hepatectomy showing Wnt2 and Wnt9b release from endothelial cells to activate -catenin in hepatocytes to induce proliferation and regain of hepatic mass.  His work also showed an important role of -catenin in hepatoblast proliferation during development and then in hepatocyte maturation. In adult liver, his group has shown that Wnt2-Wnt9b from endothelial cells also control gene expression in hepatocytes located in pericentral region of the liver lobule and hence plays an important role in metabolic zonation. He showed an important redundancy between β-catenin and β-catenin at adherens junction where loss of any one of the two catenins was compensated by the other, whereas dual loss in hepatic epithelial or ‘hepithelial’ cells, led to disruption of blood bile barrier and excessive morbidity. The second major focus in the lab has been on understanding the role of β-catenin gene mutations in liver tumors especially hepatoblastoma and hepatocellular cancer. Since mutations in CTNNB1 are observed in 26-38% of all HCC patients, he has generated very relevant mouse models that represent subset of human HCC using sleeping beauty transposon/transposase and crispr/cas9. These models have lent themselves well to help understand the cooperation of mutant CTNNB1 with other oncogenes such as MET, NFE2L2, YAP and others. Their studies have revealed β-catenin to be a driver mutation whose therapeutic targeting may have a profound impact on the field. They have identified addiction of -catenin gene mutated HCCs to mTORC1 due to excess glutamine production by these tumors, as well as resistance to immune checkpoint inhibitors due to unique biology that leads to dearth of immune cell infiltration within the tumor microenvironment. Several discoveries from his lab are now ready to be translated into the clinic and may have both diagnostic and therapeutic implications.