Alexander Dodson
Pronouns: he/him
Research Mentor(s): Robert Fontana
Co-Presenter:
Research Mentor School/College/Department: Gastroenterology / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 4 – 2:40pm – 3:30 pm
Room: League Ballroom
Authors:
Presenter: 79
Abstract
Currently, idiosyncratic drug-induced liver injury (DILI) is hard to detect in patients, often requiring careful analysis of patient past medical history and competing causes by trained medical professionals, slowing down patient treatment as well as the development process of new drugs. Investigators have attempted to produce a validated laboratory technique to analyze biologically accurate liver organoids, with the end goal of developing a test to confirm a DILI diagnosis, however none have proved viable. The Human Liver Organoid (HLO) study aims to identify drug-induced liver injury earlier and more precisely than currently accepted protocols through more accurate plating mechanisms through the use of the Emulate liver chip. The Emulate chip mimics human hepatic conditions, mirroring physiologically relevant flow and biological makeup. In order to create human liver organoids in ex-vitro conditions, we must first collect a blood sample from the patient, isolate peripheral blood mononuclear cells (PBMC’s), and send the rest to the DILIN biorepository and genetic testing centers. Then, we produce induced pluripotent stem cells (iPSC), which can later be turned into human liver organoids and plated on a 364 well 2-D plate as well as the Emulate chip system. From this point, we can modify the liver chip system by adding medications, herbal/dietary supplements (HDS), or other molecules and monitor how the organoid responds, giving a prediction for how the actual patient would respond to the treatment. Hepatotoxicity becomes apparent through clinically relevant secretions in the 2-D well plates such as the liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST), as well as reductions in albumin sythesis. As a result of the HLO study, we may be able to more quickly identify DILI in susceptible patients, leading to potentially faster drug development and quicker diagnosis for patients.
Biomedical Sciences
