Diya Gehlaut
Pronouns: she/her/hers
Research Mentor(s): Robert Fontana
Research Mentor School/College/Department: Gastroenterology / Medicine
Program:
Authors:
Session: Session 2: 10:00 am – 10:50 am
Poster: 80
Abstract
Drug-induced liver Injury (DILI) is an uncommon adverse event caused by medication, herbs, or other xenobiotics. DILI is one of the leading causes of acute liver failure in the US. Additionally, DILI can lead to regulatory actions regarding approved medications as well as early termination of drugs in development. Still, there is no objective laboratory test to confirm a diagnosis of DILI due to a drug or herb. Therefore, the overarching aim of this research project is to develop a biobank of human liver organoids (HLOs) derived from iPSCs obtained from individuals with clinically significant DILI due to a particular drug or HDS product identified by the DILIN study. We hypothesize that creating HLOs from iPSC obtained from DILIN patients will lead to the development of a sensitive and specific in vitro diagnostic test with a high level of drug specificity that is superior to that obtained from random iPSC-derived organoids. In the current study, we have developed a list of drugs to use as positive controls and negative controls for in vitro testing. These lists were curated from the 30 top single-implicated drugs and HDS products observed in the ongoing DILIN registry study from 2004 to 2022. We also used the LIVERTOX likelihood score to better refine our list of positive and negative controls. We will use these data combined with those available from FDA websites to identify a list of “Hepatotoxic” drugs to use as positive controls in our HLO work. We will also develop a list of drugs that can serve as “Negative controls” that do not cause hepatotoxicity in vitro for our future experiments.
