VHL disease modeling : Betty Gardie (2023 - 2026)

Betty Gardie is the scientific leader of the FMR funded project : Modeling VHL Hemangioblastomas Using Induced Pluripotent Stem Cells (iPSCs).

Abstract

Mutations in the von Hippel-Lindau (VHL) gene predispose individuals either to erythrocytosis, which may be associated with angiomas (benign vascular malformations), or to the development of multiple tumors, including hemangioblastoma (HB) (vascular tumors). Although benign, HBs can be severely disabling due to their location in the retina, cerebellum, and spinal cord, leading to neurological symptoms such as vision loss and motor dysfunction.

We aim to decipher the molecular mechanisms responsible for the vascular disorders associated with VHL mutations. Our hypothesis is that neural crest cells (NCC) may secrete abnormal signals that stimulate vascular proliferation. To investigate this, we model HB development using induced pluripotent stem cells (iPSCs) derived from VHL patients. These iPSCs are differentiated into NCC and endothelial cells to recreate the tumor microenvironment in vitro.

This innovative approach will enable us to identify the factors driving vascular tumor formation and pave the way for novel biomarkers and therapeutic targets for patients with VHL disease.