Periodic Reporting for period 1 - OSTtrans (The Role of OSTα/β as a Bile Acid and Drug Transporter in Obesity-Associated Chronic Liver Disease, Nonalcoholic Fatty Liver Disease)
Reporting period: 2018-09-01 to 2020-08-31
The project aimed to increase understanding of the emerging liver diseases NAFLD and NASH, particularly by evaluating the expression of transporter proteins in the liver of NAFLD and NASH patients. The information on the transporter expression in the diseases is essential for safe drug therapies and will benefit the development of new chemical entities for chronic metabolic and liver diseases. The project focus on the role of OSTα/β as a bile acid and drug transporter particularly in NAFLD. The hepatic expression of OSTα/β is normally low but dramatically increased in the conditions with elevated bile acid levels in the liver, even more than expression of other bile acid transporters. The scientific aims of the project are: 1) the proteomics of bile acid transporters in NAFLD and NASH liver, 2) regulation and mechanisms of OSTα/β transport, and 3) the role of OSTα/β as a bile acid and drug transporter in the human liver in comparison to other hepatic basolateral transporters.
Secondly, we aimed to evaluate the function and activity of the bidirectional OSTα/β transporter in human cell line overexpressing human OSTα/β (WP2). Both modulation of OSTα/β transporter by endogenous compounds and interaction of OSTα/β transporter with drugs and endogenous compounds were evaluated. The results of this work package will be published shortly. The developed in vitro methodologies are further applied by our collaborators to reveal novel OSTα/β substrates and inhibitors and evaluate drug-drug interactions.
The work arising from this project has been presented at multiple scientific meetings, but also in the meeting of community pharmacists. I presented posters at ITTS Inaugural Conference - “The Transporter Transition” (2018) and Farmasian Päivät (2018), where I gave also a talk. The work has been presented as posters also at Gordon Research Conference - Drug Metabolism (2019) and BioParadigms - 11th BioMedical Transporters Conference (2019). In addition, posters planned to be presented in conferences both in Europe and in the United States (2020).
The project will yield publications that will be found on public databases. During the fellowship, I have continued collaboration with my previous laboratory and the collaborative work initiated prior the fellowship has gained multiple publications.