Supervisor: Dr Xavier De Deken / Dr Benjamin Beck
Project Overview
This PhD project aims to identify genes and signaling pathways that drive resistance to SHIP2 inhibition—or, conversely, sensitize tumor cells to SHIP2 pharmacological inhibitors—in esophageal squamous cell carcinoma (eSCC) and head and neck squamous cell carcinoma (HNSCC). The ultimate objective is to develop rational combination strategies to improve therapeutic efficacy in these aggressive cancers.
Recent work at IRIBHM has established SHIP2 (INPPL1), a key regulator of the PI3K/AKT signaling pathway and of cell cycle progression, as a promising therapeutic target in eSCC (PMID: 41188852 ; 41198465). However, adaptive cell resistance limits the durability of the drug response. This project will leverage state-of-the-art functional genomics to systematically uncover the molecular determinants of resistance and vulnerability to SHIP2-targeted therapies.
Research Objectives
- Perform genome-wide CRISPR/Cas9 loss-of-function screens in human eSCC and HNSCC models.
- Identify genes and pathways that confer drug resistance or, alternatively, enhance sensitivity to SHIP2 inhibition.
- Functionally validate top candidates and characterize their impact on cancer cell survival, proliferation, and signaling in vitro.
- Translate genetic vulnerabilities into rational drug combinations to overcome resistance and potentiate SHIP2-based therapies in vivo and in vitro.
Scientific Environment
The project will be conducted at IRIBHM, a leading research institute at ULB with strong expertise in cancer biology, signal transduction, and functional genomics. The PhD candidate will benefit from close supervision by Prof. Xavier De Deken and Dr. Benjamin Beck, access to cutting-edge molecular biology platforms, and a collaborative, international research environment.
Candidate Profile
We seek a highly motivated candidate with:
- A Master’s degree in molecular biology, biomedical sciences, or a related discipline.
- Strong interest in cancer biology and targeted therapies.
- Experience in cell culture, molecular biology techniques, and/or CRISPR-based approaches is highly desirable.
- Ability to work independently, critically analyze data, and collaborate in a multidisciplinary setting.
Why Apply?
This PhD offers the opportunity to:
- Gain advanced training in genome-wide screening, mechanistic biology, and translational research.
- Conduct innovative, high-impact research on cancer therapeutics.
- Contribute directly to the development of novel combination strategies for difficult-to-treat cancers.