ÌÇÐÄvlogÃÛÌÒ The Lab
Our laboratory conducts basic and translational research focused on the pathogenesis and treatment of neonatal liver diseases, with a primary emphasis on cholestasis and parenteral nutrition-associated liver injury. The cornerstone of our lab is a unique neonatal piglet model that allows for complex surgical and nutritional studies, closely mimicking human infantile liver diseases like biliary atresia and parenteral nutrition-associated cholestasis (PNAC). Our overarching goal is to identify novel mechanisms of liver injury and develop targeted therapeutic strategies for vulnerable pediatric populations by building a translational bridge between basic science and clinical care.
A key focus of our current work is to elucidate the mechanisms driving fibrosis and inflammation in neonatal obstructive cholestasis. We are investigating the role of the gut-liver axis, specifically how gut-derived bacterial products contribute to endotoxemia and subsequent liver fibrosis. This includes evaluating therapeutic agents, such as Rifaximin, to modulate the gut microbiome and reduce the inflammatory cascade that promotes liver injury.
Furthermore, a significant portion of our research examines the impact of nutrition on metabolic function and liver health in neonates, particularly those born prematurely or requiring long-term parenteral nutrition. We are exploring how critical nutrients like choline influence metabolic pathways and how specific components of parenteral nutrition, such as various lipid emulsions and phytosterols, contribute to liver disease. Our lab employs an integrative experimental approach that spans from whole-animal physiology to cellular and molecular biology to address these complex clinical questions.
Primary Investigator
My research centers on understanding the mechanisms that drive the development of parenteral nutrition associated liver disease in neonates on long-term parenteral nutrition. My current focus is the role of lipid emulsion constituents on causing the disease progression. This research is performed on a neonatal piglet model in order to assess both physiologic and molecular alterations that are similar to those seen in neonates.
Lab Projects
Our lab investigates the impact of perinatal nutrition on overall health and liver function, particularly in premature infants requiring parenteral nutrition. We are exploring how essential nutrients like choline influence metabolic pathways and how specific components of parenteral nutrition, including lipid emulsions and phytosterols, contribute to liver disease. This research is supported by a USDA grant (2024-2029).
This project is focused on characterizing the molecular regulation of hepatobiliary bile acid homeostasis. We seek to understand how these critical pathways are disrupted in neonatal cholestasis and how they can be targeted for therapeutic intervention. This work is currently funded by an NIH NIDDK grant (2021-2026).
This project investigates the role of the gut-liver axis in liver injury, specifically how gut-derived bacterial products promote endotoxemia and fibrosis. We are evaluating the potential of Rifaximin, a gut-selective antibiotic, as a therapeutic agent to modulate the gut microbiome, reduce inflammation, and prevent fibrosis in neonatal cholestasis. This work is currently funded by an NIH NIDDK grant (2025-2027).
Publications
Guthrie G, Vonderohe C, Meléndez Hebib V, Stoll B, Burrin D. Multicomponent parenteral lipid emulsions do not prevent liver injury in neonatal pigs with obstructive cholestasis. JCI Insight. 2025;10(10). Epub 20250417. doi: 10.1172/jci.insight.189196. PubMed PMID: 40244694; PMCID: PMC12128955.
Guthrie G, Stoll B, Chacko S, Mohammad M, Style C, Verla M, Olutoye O, Schady D, Lauridsen C, Tataryn N, Burrin D. Depletion and enrichment of phytosterols in soybean oil lipid emulsions directly associate with serum markers of cholestasis in preterm parenteral nutrition-fed pigs. JPEN J Parenter Enteral Nutr. 2022;46(1):160-71. Epub 20210430. doi: 10.1002/jpen.2088. PubMed PMID: 33581699; PMCID: PMC8361868.
Guthrie G. Parenteral Nutrition Associated Hepatic Steatosis and NAFLD Intersect at AMPK. Cell Mol Gastroenterol Hepatol. 2022;14(3):724-725. doi: 10.1016/j.jcmgh.2022.06.005. Epub 2022 Jul 7. PubMed PMID: 35810785; PubMed Central PMCID: PMC9421576.
Guthrie G, Vonderohe C, Burrin D. Fibroblast growth factor 15/19 expression, regulation, and function: An overview. Mol Cell Endocrinol. 2022 May 15;548:111617. doi: 10.1016/j.mce.2022.111617. Epub 2022 Mar 15. Review. PubMed PMID: 35301051; PubMed Central PMCID: PMC9038700.
Call L, Molina T, Stoll B, Guthrie G, et al. Parenteral lipids shape gut bile acid pools and microbiota profiles in the prevention of cholestasis in preterm pigs. J Lipid Res. 2020;61(7):1038-51. Epub 20200429. doi: 10.1194/jlr.RA120000652. PubMed PMID: 32350078; PMCID: PMC7328048
USDA/ARS Children's Nutrition Research Center
The Guthrie Lab is part of the USDA/ARS Children's Nutrition Research Center which houses laboratories, state-of-the-art equipment, a greenhouse, observation labs, research volunteer accommodations, a metabolic kitchen, and an elite group of research scientists.
Contact Us
Children’s Nutrition Research Center
1100 Bates St
Office: 713-798-0343
Fax: 713-798-7057
Email: Gregory.Guthrie@bcm.edu