Functional characterization and targeting of the neuroblastoma stem cell

The knowledge of normal embryonic development of a cell lineage is key to understand the heterogeneity and progression of cancer arising from this particular lineage. Cancer cells replay gene expression modules active during developmental dynamics in specific microenvironments.

Indeed, the interactions between the tumor and its microenvironment are often critical to uncovering the mechanisms of tumor survival.

Our preliminary data has identified malignant Schwann Precursor cells (tSCPs) as the putative neuroblastoma stem cell.

We believe that tSCPs produce malignant adrenergic and mesenchymal cell-states and facilitate the survival of the tumor.

Building on our expertise with preclinical modeling, we will generate in vitro and in vivo models that recapitulate tSCPs, that will be further used to characterize the function and preclinical targeting of these cells.

Moreover, we have already used our single-cell profiling data on human neuroblastoma and normal fetal sympatho-adrenal tissue to identify the sources and nature of microenvironment signals that channel sympatho-adrenal differentiation during normal development.

By contrasting interactions in normal fetal and neuroblastoma tissue, we aim to target factors, pathways, or signals that would push tSCP towards terminally differentiated tumor cell fates with the long-term goal to cure childhood neuroblastoma.