Gastroenterology, Hepatology and Nutrition
Huppert Lab

Huppert Research Lab

The Huppert Lab is interested in intercellular signaling pathways that regulate cell fate decisions and lineage restriction during organogenesis and adult cell population renewal. Our projects use genetic, chemical and surgical mouse models, as well as primary cell lines to answer questions related to liver development and regeneration.

The liver is a vital organ for metabolism and homeostasis and has the highest regenerative capacity of all parenchymal organs. The architecture of the liver biliary and vasculature systems is absolutely crucial for the overall health of the organ and the ability to perform its endocrine and exocrine functions. Generating continuity between canalicular networks and establishing the biliary and vascular systems within the growing parenchymal mass involves finely tuned complex morphological and molecular mechanisms. The lack of knowledge relating important hepatic dimensional aspects limits our understanding of how paracrine and autocrine signals directly regulate or indirectly influence the intact communicating architecture and physiology. Our long-term goal is to define the molecular factors and cellular contribution required for formation of the two- and three-dimensional hepatic architecture, during hepatic morphogenesis, homeostasis and regeneration.

It is our hope that by elucidating the molecular mechanisms that guide cell-cell communication, epithelial-mesenchymal interactions and lineage restriction in the liver, we will gain novel insights into how defects in normal processes are dysregulated in congenital and chronic liver diseases.

The Huppert Lab trains graduate students who are in the Molecular and Developmental Biology Graduate Program, and the Cancer and Cell Biology Graduate Program.

Advancements in Treating Alagille Syndrome

Having fewer bile ducts than normal is caused by various liver diseases, including Alagille syndrome. In Alagille syndrome, most patients have a mutation in the gene called JAG1, which results in a lack of bile ducts. Lack of bile ducts can lead to liver damage and potentially the need for a liver transplant. Teams led by Dr. Huppert (Cincinnati Children's) and Dr. Jafar-Nejad (Baylor College of Medicine) explored whether decreasing the expression of the Poglut1 gene in a mouse would help restore bile ducts.

The teams grew mice who were born with Alagille syndrome and gave these mice two injections of an antisense therapy, (ASO)-targeting Poglut1, at birth. The mice who received the ASO injections experienced restoration of their bile ducts. Even the mice with severe bile duct abnormalities showed improved bile duct anatomy after the injections. Thus, they did not display liver disease or liver damage. This is a big step towards identifying a possible treatment for children whose liver disease is related to a lack of bile ducts. Read the abstract