The objective of this proposal is to established undifferentiated iPSCs as a diagnostic tool for the prediction of nonalcoholic fatty liver disease onset and severity.
Despite the widespread estimated prevalence of NAFLD, there are currently no tools available to predict likelihood of NAFLD susceptibility beyond standard clinical and demographic information.
Major Proposed Activities
- Create an iPSC-based NAFLD risk score (iPSC-RS) by defining threshold values for oleate-induced intracellular lipid accumulation that distinguish iPSCs from NAFLD patients versus healthy controls.
- Validate the iPSC-RS in an independent set of iPSCs from 25 NAFLD cases and 25 healthy controls, and evaluate the it's reproducibility across biological replicates and independent laboratories.
- Compare the validated iPSC-RS to other NAFLD risk predictors based on genomic information alone.
Nonalcoholic fatty liver disease (NAFLD) is a widely undiagnosed condition, and is estimated to impact up to 30% of adults. NAFLD is most prevalent in Hispanics, with the absolute highest levels found in individuals of Mexican ancestry, and thus is relevant to California's LatinX population. As NAFLD is anticipated to become the leading cause of liver transplant, identifying Californians most at risk could address significant gaps in screening and prevention for this serious disease.