686889 event 1765813776 1765813820 Seong Hu Kim
BME PhD Proposal Presentation

Date: 2025-12-15
Time: 2:00 PM-4:00 PM
Location / Meeting Link: HSRB II N100

Committee Members:
Karmella Haynes, PhD (Advisor); Hanjoong Jo, PhD; Tara Deans, PhD; Young Jang, PhD; Jitendra Thakur, PhD


Title: Reversal of Oncogene-Induced Cellular Senescence in Human Lung Fibrobalst Cells with Epigenetic Tools

Abstract:
Cellular senescence, a state of stable cell-cycle arrest implicated in aging and age-related pathologies, is maintained by extensive chromatin remodeling that renders current reversal strategies inconsistent. This project seeks to overcome this barrier by developing programmable epigenetic tools to precisely remodel the senescent epigenome and reverse oncogene-induced senescence (OIS) in human lung fibroblasts. We propose two complementary engineering strategies: first, the deployment of synthetic reader actuators (SRAs) that couple H3K27me3-binding domains with transcriptional effectors, utilizing interpretable machine learning to predict and selectively rewire silenced gene networks; and second, the creation of modular synthetic long non-coding RNAs (lncRNAs) derived from XIST machinery to nucleate repressive heterochromatin at the CDKN2A/CDKN2B locus. By defining quantitative design rules for these chromatin- and RNA-targeting modalities, this research aims to establish a validated framework for epigenetic senoreversion, offering a transformative therapeutic paradigm that restores cellular proliferative potential rather than relying on the ablation of senescent cells.

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