Functional genomic analysis of patient-derived pre-clinical models of renal cancers to identify novel therapeutic targets

Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer. Its metastatic form (mRCC) remains incurable and resistant to chemotherapy and radiation. Current treatments targeting the tumor microenvironment offer limited benefit, highlighting the need for new strategies based on disease biology. ccRCC is difficult to target due to its cellular heterogeneity and limited understanding of its vulnerabilities.
Our lab’s single-cell RNA sequencing (scRNA-seq) of patient-derived xenograft (PDX) models identified a subpopulation of cells with progenitor-like features capable of differentiating into multiple tumor cell types. These findings support the existence of cancer stem cells (RCC-CSCs) driving tumor growth, aggressiveness, and therapy resistance.
This project aims to identify essential genes for RCC development by targeting RCC-CSCs. From scRNA-seq data, we identified genes upregulated in RCC-CSCs and will perform a focused CRISPR-Cas9 dropout screen in patient-derived 3D organoid models to pinpoint genes required for tumor initiation and maintenance.
The screening will take place in Dr. Michael Boettcher’s lab at Martin Luther University Halle-Wittenberg, leveraging expertise in CRISPR functional genomics. Results will define RCC-CSC vulnerabilities and guide new therapeutic approaches for metastatic ccRCC, a currently incurable malignancy.

Faculty Supervisor:

Yasser Riazalhosseini

Student:

Partner:

Martin Luther University of Halle-Wittenberg

Discipline:

Life Sciences

Sector:

Health and Related Sciences and Technology; Biotechnology

University:

McGill University

Program: