Antonis Kourtidis, Ph.D.
Research Project Leader 2022
Department of Regenerative Medicine and Cell Biology
Kourtidis Lab
Overview
Dr. Kourtidis’s research established a novel mechanistic link between epithelial cell–cell adhesion and RNA-based gene regulation.
The project tested the hypothesis that the adherens junction protein PLEKHA7 recruits the RNA interference (RNAi) machinery to epithelial junctions, enabling localized control of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). This spatial regulation maintains epithelial integrity and suppresses oncogenic signaling pathways in the colon.
Specific Aims
- Define how PLEKHA7 recruits RNAi machinery to suppress the oncogenic lncRNA MIR17HG.
- Determine how PLEKHA7-mediated regulation of MIR17HG controls epithelial integrity and tumorigenesis
Research Approach
The project combined molecular, cellular, and in vivo approaches to define the PLEKHA7–RNAi–lncRNA regulatory axis. RNA-protein interaction assays, CRISPR-based gene editing, and advanced imaging techniques were used to define how RNAi components localize to adherens junctions. Functional analyses were performed in colon epithelial cell lines, patient samples, and organoid systems. Mouse models and CRISPR-engineered systems were used to determine the contribution of this pathway to intestinal homeostasis and tumor development.
Use of the Center's Core Resources
Cell Models Core
- Generation of CRISPR-edited cell lines and organoids
Advanced Imaging Core
- Localization of RNAi machinery, lncRNAs, and junctional complexes
Animal Models Core
- In vivo models of epithelial dysfunction and tumorigenesis
Innovation
- Reveals a previously unknown link between cell adhesion and RNA interference pathways
- Identifies spatial regulation of lncRNAs at adherens junctions as a novel control mechanism
- Establishes PLEKHA7 as a regulator of oncogenic lncRNAs and epithelial homeostasis
Impact and Outcomes
This work defines a new paradigm in epithelial biology by linking structural cell adhesion complexes with RNA-mediated gene regulation. By identifying how dysregulation of PLEKHA7 and lncRNAs such as MIR17HG contributes to colorectal cancer, this project provides new opportunities for biomarker development and targeted therapies. Participation in the Center for Biomedical Research Excellence in Digestive & Liver Disease's program supported Dr. Kourtidis’s development as an independent investigator and established a research program at the interface of cell biology, RNA regulation, and cancer.
