Establishment and Validation of an IPS-based Neuroblastoma Model

Background

Neuroblastoma is the most common extra-cranial solid childhood cancer, accounting for 15% of all cancer deaths in children. Targeted therapies hold promise to improve the outcome for children with high-risk neuroblastoma, however this issue remains challenging. Amplification of the MYCN oncogene occurs in half of high-risk patients.

Our previous studies have shown that targeted expression of MYCN can drive neuroblastoma in transgenic mice, and in human induced pluripotent stem cells, differentiated to neural crest (cell of origin) and implanted orthotopically in immunocompromised hosts. These in-vivo models share phenotypes found in human high-risk neuroblastoma, and respond to MYCN-directed therapies, suggesting MYCN as a critical therapeutic target for neuroblastoma.

Project Goal

Colin will learn to express MYCN-GFP in a human iPS cell-based system to generate a model for high-risk neuroblastoma suitable for screening small molecules. He will test initiate chemical genetics screens and perform data analysis. Specifically, Colin will grow human iPS cells, differentiate them into neural crest cells, and transduce MYCN-GFP lentivirus into the cells. He will use Flow Cytometry to sort out GFP-positive cells and test if CD532 will reduce the GFP signal. Successful completion of this summer research will set up a system for the Weiss lab to initiate screens for better MYCN-blocking therapies.