Reben Raeman, MS, PhD*
S408 Biomedical Science Tower
200 Lothrop Street
Pittsburgh, PA 15261
The primary focus of our lab is to elucidate host and environmental factors driving hepatic inflammation and fibrosis in non-alcoholic steatohepatitis (NASH). NASH is an advanced and progressive form of non-alcoholic fatty liver disease affecting ~16.5 million people in the US. An estimated one in six patients with NASH progress to cirrhosis, and NASH-related cirrhosis is now the 2nd leading cause of liver transplantation in the US. Consequently, there is an urgent need to devise novel therapeutic interventions to halt progression of NASH, as no therapies currently exist. We have recently established that gut microbial antigens are among the primary drivers of hepatic inflammation and fibrosis in NASH. Our findings also underscore the importance of diet-induced gut dysbiosis, mucosal inflammation, and subsequent disruption of the intestinal epithelial barrier in NASH. The mouse model of compromised intestinal epithelial barrier we used for these studies turned out to be an excellent dietary model of NASH. When fed a Western diet, these mice not only develop key features of MetS, but also develop hepatic inflammation and fibrosis. Using this novel preclinical model, we are performing further studies to gain mechanistic insights into the etiology of NASH progression. Our overarching goal is to dissect the complex interplay between intestinal epithelial barrier, gut microbial dysbiosis, and immune dysregulation in NASH. The ultimate goal of our research is to devise preventative and therapeutic modalities for the clinic.
We are currently exploring three major questions:
1. How does gut microbiota modulate intestinal epithelial barrier permeability and mucosal immunity in NASH?
2. Role of adaptive immune responses, specifically T cells, in regulating hepatic inflammation in NASH.
3. How do diet induced changes in bile acid composition impact colonic epithelial barrier?
Department of Pathology