Chronic Liver Disease
Jaimie D. Nathan, MD
Assistant Professor
Department of Pediatrics; Division of General and Thoracic Surgery
Description of Research
Dr. Nathan is a new surgery faculty member developing a laboratory research program to elucidate cellular and molecular mechanisms of liver injury induced by the chronic administration of parenteral nutrition (PN), also known as PN-induced liver disease (PNALD). This is a very important cause of liver disease in infants who require PN support as neonates or during early life. While end-stage liver disease is a well-known consequence of long-term PN dependence, the cellular and molecular mechanisms that result in PNALD have not been well established, but have been proposed to be multifactorial. Dr. Nathan is currently developing a novel animal model of PNALD combining small bowel bacterial overgrowth/bacterial translocation with parenteral nutrition administration. To induce small bowel bacterial overgrowth, he established a surgical approach to create a small bowel self-filling blind loop, and preliminary analyses demonstrate significant bacterial overgrowth in the blind loop, substantial mucosal inflammation within the loop, and bacterial translocation to draining mesenteric lymph nodes. Mice also have histological and biochemical evidence of liver inflammation, and will serve as a basis for further studies to identify the mechanism by which small bowel bacterial overgrowth contributes to liver inflammation. Dr. Nathan anticipates that the addition of PN administration to the model of small bowel bacterial overgrowth will result in a more severe, and more clinically relevant, PNALD phenotype, and that this model will serve as the basis for further studies to elucidate cellular mechanisms involved in the pathogenesis of PNALD.
Collaborations
Dr. Nathan works with Drs. Bezerra and Kohli to study the mechanisms of liver injury. Additionally, he collaborates with Dr. Helmrath examining intestinal responses to bacterial overgrowth in the small bowel self-filling blind loop model. Projection of Core use: Gene and Protein Expression, Bioinformatics, and Integrative Morphology Cores.
