Robert F. Schwabe, MD
- Associate Professor of Medicine
My research seeks to elucidate mechanisms by which fibrosis and cancer develop in the chronically injured liver using mouse models, patient samples as well as novel Systems Biology approaches. To understand the contribution of liver fibroblasts and the underlying pathways, my lab has generated hepatic stellate cell-selective Cre transgenic mouse (LratCre), allowing to trace and functionally manipulate hepatic stellate cell (HSC)-derived fibroblasts. Current efforts are to delineate the contribution of HSC to different types of injury and fibrosis, including non-alcoholic steatohepatitis (NASH), with the ultimate goal to identify novel druggable pathways that promote HSC activation and liver fibrosis. Besides fibrosis, my lab also investigates liver cancer development. Liver cancer is the second leading cause of cancer mortality world- wide, and almost never develops in healthy livers. In most patients, liver cancer develops after decades of chronic liver injury, inflammation and fibrosis, supporting the notion that liver cancer is “a wound that does not heal”. One interest of my laboratory is to unravel the relationship between fibrosis and cancer development. Using mouse models, we try to understand whether fibroblasts and ECM promote the development of hepatocellular carcinoma (HCC) using LratCre mice to ablate or functionally manipulate cancer-associated fibroblasts (CAF) in liver carcinogenesis. In addition, my laboratory is interested in the role of fibrosis and CAF in the development of cholangiocarcinoma (CCA). Using above-described tools such as LratCre-transgenic mice, we seek to uncover how the absence or inactivation of stellate cell-derived CAF and ECM proteins affects CCA development. Key data are confirmed using bulk and single cell RNA-sequencing as well as novel Systems Biology approaches in patient samples. Finally, my lab seeks to uncover druggable "master regulators" in HCC and CCA using novel Systems Biology approaches in collaboration with the Califano lab.
Filliol A, Schwabe RF. FoxM1 induces CCl2 secretion from hepatocytes triggering hepatic inflammation, injury, fibrosis, and liver cancer. Cell Mol Gastroenterol Hepatol. 2020; 9(3):555-556. PMID: 32008983
Hernandez C, Huebener P, Pradere JP, Antoine DJ, Friedman RA, Schwabe RF. HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis. J Clin Invest. 2018; 128(6):2436-2451. PMID: 29558367
Yu LX, Schwabe RF. The gut microbiome and liver cancer: mechanisms and clinical translation. Nat Rev Gastroenterol Hepatol. 2017; 14(9):527-539. PMID: 28676707