Dr. Arteel’s research focuses on the interaction between hepatotoxicants (e.g., arsenic) and lifestyle choices (e.g., obesity and alcohol) in the initiation and progression of chronic liver diseases. His current research foci are based on the understanding that transitional changes to the ECM proteome (i.e., “matrisome”) play an underappreciated role in the initiation and progression of liver disease. He is developing computational tools to attempt to predict mechanism(s) and to develop biomarkers (or surrogate biomarkers) for use in the clinics.

 

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Dr. Beier’s research focus is on environmental vinyl chloride exposure in the context of existing underlying liver disease. Clearly high occupational exposure to vinyl chloride is directly hepatotoxic; what is less well clear is the impact of lower environmental exposure on exacerbating existing liver disease. Given the fact that a significant portion of the population has risk factors for liver disease (most commonly, obesity), and that 30% of the US population has elevated indices of liver damage, any potential impact of low environmental exposure could be dramatic. Our findings indicate that vinyl chloride will exacerbate liver damage caused by another factor. This work shifts the paradigm of current risk assessment for not only this compound, but for any other environmental agent that may potentially damage the liver.
 

 

 

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Dr. Duarte-Rojo conducts clinical and translational research in disorders of physical function and exercise in advanced liver disease. He is also interested in clinimetrics, with an emphasis on the use of noninvasive assessment of liver disease, and the development of methods to predict clinical outcomes.
 

 

 

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Dr. Jonassaint’s researches specific biologic markers involved in the development and progression of liver disease in both the pre- and post- transplant populations, with a focus on disparities in liver transplant outcomes. This research program also explores why some patients experience rapid fibrosis progression or accelerated graft loss post-transplant.

Dr. Monga ‘s current research projects are aimed at elucidating the cellular and molecular mechanisms of liver pathophysiology. His lab is interested in understanding the process of liver regeneration. Using genetic knockout mice (inducible, conditional), his lab is in the process of determining the cell-molecule circuitry of the Wnt signaling during liver regeneration process. Similarly, the lab studies the regulation of the process of metabolic zonation where hepatocytes in different zones of the hepatic lobule are bestowed with different functional capacities owing to the differential gene expression. The pericentral gene expression is under the control of Wnt signaling, and the periportal gene signature has been suggested to be under the control of Yap signaling. This process of dynamic interactions between the two signaling pathways is also under investigation. Since hepatic repair after various injuries is dictated by the kind of injury and type of cell affected, several studies have shown the potential of hepatocytes and biliary epithelial cells to transdifferentiate into one another. We are examining the models and the molecular mechanisms that underlie these processes so as to exploit them for regulating repair process. A major sequela of multiple chronic liver diseases is in fact development of hepatic fibrosis. This involves in large part activation of hepatic stellate cells to form activated myofibroblasts, which are the source of collagen and scarring in the liver with the eventual development of cirrhosis. We are examining molecular signals that are relevant in stellate cell activation and biology, which can be targeted for development of anti-fibrotic therapies. Similarly, we are interested in role of macrophages in hepatic injury and repair process and their crosstalk with stellate cells. A common form of hepatic injury is cholestatic, where there is an impairment of bile flow in the liver causing retention of bile acids and injury to hepatic parenchyma as well as breach of blood bile barrier that results in bilirubin and bile acid leaking into systemic circulation. Using animal models, we are looking at novel ways to modulate bile acid metabolism to counteract cholestatic liver injury and repair. Similarly, we are investigating novel mechanisms that underlie the pathogenesis of various cholestatic liver diseases. We have identified the important role of adherens junctions, tight junctions, and desmosomes in maintenance of blood bile barrier through unique mechanisms and crosstalk. We have generated animal models to address such mechanisms and using innovative imaging methodologies like intravital microscopy, we have identified peculiar underpinnings of disorders such as PFIC. We hope to devise novel therapeutic interventions based on new findings. Lastly, we are interested in another relevant sequela of many chronic liver diseases. Liver tumors—especially hepatocellular cancer—develops mostly in the backdrop of chronic liver injury. We are interested in identifying patient-relevant molecular aberrations, and using a reductionist approach, we generate animal models to address biology and therapies. We use sleeping beauty transposon/transposase and hydrodynamic tail vein injections to deliver the plasmids into 1-5% of hepatocytes in a mouse to examine tumorigenesis. Using high throughput analysis of tumors (gene array), we are addressing gene expression changes, which are then correlated with existing human HCC databases, such as TCGA, to address the similarity of the animal model to the human disease. Such validation allows us to more confidently use this model as a representative of a subset of human HCC. Such approaches have also yielded novel information about other liver tumors like hepatoblastomas.

Dr. Rabinovitz studies the assessment and treatment of chronic viral hepatitis, focusing on combination therapy for chronic hepatitis C patients. Additional research efforts focus on developing new therapies for non-alcoholic fatty liver disease (NALFD), biological agents for patients with low platelet count undergoing invasive procedures, and new therapies for patients with hepatic encephalopathy.

Dr. Shaikh researches the progression of end-stage liver disease, treatment of hepatocellular carcinoma, hepatocarcinogenesis and genomic profiling of liver tumors, and allocation models for liver transplantation.