Deciphering ALK Signaling for Effective Therapeutic Targeting of ALK-Driven Neuroblastoma

This project aims to understand Anaplastic Lymphoma Kinase (ALK) and its role in normal and pathological developmental processes. ALK was first described in the 90s, as the NPM-ALK fusion protein, in non-Hodgkin´s lymphoma.

Since then, oncogenic activation of ALK has been reported in a wide range of cancers, including non-small cell lung cancer and childhood neuroblastoma.

The Palmer lab has investigated ALK and mapped critical components of the ALK signalling network in cell, Drosophila and mouse models, ranging from the description of fundamental mechanisms of ALK function to undertaking rigorous preclinical analysis of ALK TKIs in a neuroblastoma setting.

The work proposed in this project will employ predominantly Drosophila and mouse models, including a unique ALK-TurboID mouse, in combination with ‘omics’ technologies to address ALK regulation and function.

Our specific aims combine DNA, single cell RNA and protein analyses together with bioinformatics and wet-lab validation to explore ALK signaling in developmental and neuroblastoma contexts.

In addition, we will continue to develop our current proteomics based investigation of patient tumour samples for integration with current state-of-the-art clinical analyses of neuroblastoma patients.

Our track record over recent years, e.g. our identification of the ALK ligands and development of mouse models of ALK-driven NB, supports our ability to achieve these aims over the next decade.