Yujie Ding
Pronouns: she/her
Research Mentor(s): Stefan Sweha
Co-Presenter:
Research Mentor School/College/Department: Department of Pathology / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 4 – 2:40pm – 3:30 pm
Room: League Ballroom
Authors: Stefan Sweha, Yujie Ding
Presenter: 94
Abstract
Recurrent mutations in isocitrate dehydrogenase 1 (IDH1) have been identified in gliomas, and these tumors are associated with poor outcomes and limited treatment options. Metabolic reprogramming in cancer cells has downstream consequences for gene expression and epigenetic modification in the nucleus. Notably, both histone acetylation and methylation mechanisms reflect the metabolic state of a cell. IDH1 normally catalyzes the cytosolic conversion of isocitrate to alpha-ketoglutarate, an important cofactor for histone demethylation reactions. The mutations of IDH proteins disrupt this process and instead IDH1 gains the ability to convert isocitrate to 2-hydroxyglutarate (2-HG). 2-HG competitively inhibits demethylation reactions and leads to a hypermethylator phenotype within cancer cells. Recent work has demonstrated that mutant IDH proteins can regulate a key mitochondrial transporter, SLC25A1, that exports citrate (an upstream source of isocitrate) to the cytosol. This project aims to uncover the mechanism by which IDH proteins regulate the expression of this transporter. Ultimately, the goal of this work is to understand how SLC25A1 expression and function cause changes in the epigenome of IDH mutant tumors and whether these changes present new targets for therapy. We will determine whether direct targeting of SLC25A1 using genetic and pharmacological methods can cause reversible epigenetic changes and determine if such targeting presents opportunities for synthetic lethality approaches both in vivo and in vitro.
Biomedical Sciences, Interdisciplinary, Natural/Life Sciences, Natural/Life Sciences
