Bruno Hagenbuch

Research

Overview

Transport proteins control the selective transport of molecules across membranes and are required for the proper function of cells. With regard to pharmacology, drug transport proteins are involved in the disposition of all drugs and are important determinants of whether drugs will reach their therapeutic targets. Modulation of the function of these drug transporters by other drugs and by disease states can lead to serious clinical disorders or severe drug-drug interactions. Our research focus is mainly on uptake transporters expressed at the basolateral membrane of human hepatocytes, such as the organic anion transporting polypeptides OATP1B1 and OATP1B3, the sodium-dependent bile salt uptake transporter NTCP, and the organic cation transporter OCT1. We recently demonstrated that several of these transporters interact with each other and affect each other's function and localization. We are currently investigatingthe underlying mechanisms of these interactions and how fatty liver disease, found in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), will affect the localization and function of these transporters.One hypothesis we are testing is that free cholesterol, which is enriched in fatty livers, and palmitoylation, regulate the function, localization, and protein interaction of these transporters. Concerning toxicology, we have ongoingcollaborations to characterize the transporter-mediated disposition of the “forever chemicals,” perfluorinatedcompounds that are environmentally stable and sometimes have very long half-lives in humans.

• Villanueva, C., E, Hagenbuch, B. 2023. Palmitoylation of solute carriers.. Biochemical pharmacology, 215, 115695
• Schnegelberger, R., D, Steiert, B, Sandoval, P., J, Hagenbuch, B. 2022. Using a competitive counterflow assay to identify novel cationic substrates of OATP1B1 and OATP1B3.. Frontiers in physiology, 13, 969363
• Ruggiero, M., J, Malhotra, S, Fenton, A., W, Swint-Kruse, L, Karanicolas, J, Hagenbuch, B. 2022. Structural Plasticity Is a Feature of Rheostat Positions in the Human Na⁺/Taurocholate Cotransporting Polypeptide (NTCP).. International journal of molecular sciences, 23 (6)
• Idowu, J., Y, Hagenbuch, B. 2022. Free Cholesterol Affects the Function and Localization of Human Na⁺/Taurocholate Cotransporting Polypeptide (NTCP) and Organic Cation Transporter 1 (OCT1).. International journal of molecular sciences, 23 (15)
• Ruggiero, M., J, Miller, H, Idowu, J., Y, Zitzow, J., D, Chang, S-C, Hagenbuch, B. 2021. Perfluoroalkyl Carboxylic Acids Interact with the Human Bile Acid Transporter NTCP. Livers, 1 (4), 221-229
• Andersen, M., E, Hagenbuch, B, Apte, U, Corton, J., C, Fletcher, T, Lau, C, Roth, W., L, Staels, B, Vega, G., L, Clewell, 3rd, H., J, Longnecker, M., P. 2021. Why is elevation of serum cholesterol associated with exposure to perfluoroalkyl substances (PFAS) in humans? A workshop report on potential mechanisms.. Toxicology, 459, 152845
• Ruggiero, M., J, Malhotra, S, Fenton, A., W, Swint-Kruse, L, Karanicolas, J, Hagenbuch, B. 2021. A clinically relevant polymorphism in the Na⁺/taurocholate cotransporting polypeptide (NTCP) occurs at a rheostat position.. The Journal of biological chemistry, 296, 100047
• Fenton, A., W, Page, B., M, Spellman-Kruse, A, Hagenbuch, B, Swint-Kruse, L. 2020. Rheostat positions: A new classification of protein positions relevant to pharmacogenomics.. Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents, 29 (7), 1133-1146
• Zhang, Y, Ruggiero, M, Hagenbuch, B. 2020. OATP1B3 Expression and Function is Modulated by Coexpression with OCT1, OATP1B1, and NTCP.. Drug metabolism and disposition: the biological fate of chemicals, 48 (8), 622-630
• Zhang, Y, Hagenbuch, B. 2019. Protein-protein interactions of drug uptake transporters that are important for liver and kidney. (Invited Review). Biochemical Pharmacology, 168, 384-391