Sanjana Chimalakonda
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: Oral5
Session: Session 4 – 2:40pm – 3:30 pm
Room: Breakout room 3
Authors:
Presenter: 2
Abstract
Recent work in the field has shown that IDH proteins can regulate the expression of key mitochondrial transporters like SLC25A1, which output alpha-KG and citrate into the cytosol where they can be used in cellular reactions. This project aims to uncover the mechanism by which IDH proteins regulate the expression of this transporter and understand how its expression and function causes changes in the epigenome of IDH mutant tumors. We also aimed to uncover whether these changes present new targets for therapy. This was done by performing a series of western blots to screen various compounds and treatments against metabolites like 2-HG that are directly related to the presence of mutant IDH. In addition, we also performed genetic knockdowns on the SLC25A1 transporter to determine its downstream effects on epigenetic modifications and tumor cell growth in vitro. **We have preliminary data suggesting that SLC25A1 activity contributes to cell growth and proliferation, and that there is a growth defect in cells with reduced SLC25A1 expression. In addition, there is patient data showing that patients with different SLC25A1 levels have different outcomes for survival. Together, these results suggest that this transporter is used by cancer cells to drive tumor progression. Cellular biological mechanisms and histone acetylation levels need to be further studied to make in-depth conclusions that will greatly impact research and patient care. In addition the pathways downstream of SLC25A1 need to be further studied and may provide a promising way to target and treat mutant IDH gliomas.
Biomedical Sciences, Interdisciplinary, Natural/Life Sciences, Natural/Life Sciences
