Wolpaw Laboratory Research Overview



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The Wolpaw Lab's work has centered on the childhood tumor, neuroblastoma. Neuroblastoma cells can exist in one of two epigenetic or lineage states, an "adrenergic" state that comprises the majority of the bulk tumor and tends to be responsive to chemotherapy, and a "mesenchymal" state that is a more minor subpopulation and more resistant to chemotherapy.

Researchers in the Wolpaw Lab found that the mesenchymal cells are much more sensitive to inflammatory stimuli and have a higher basal level of inflammation than the adrenergic cells, revealing a potential immune vulnerability of this important drug-resistant state.

The Wolpaw Lab is investigating how to model these states and how to exploit that vulnerability to enhance therapy for neuroblastoma patients. The researchers are also interested in applying similar principles to other pediatric solid tumors.

We are working to develop and characterize immunocompetent mouse models of lineage heterogeneity in neuroblastoma, in order to investigate the impact of these states on immunotherapeutic responses.

IHC Example

Our prior work showed that the mesenchymal lineage state has functional signaling through multiple inflammatory sensors, including those involved in dsRNA and cytosolic DNA sensing, but the adrenergic state does not. We are using CRISPR-Cas9 approaches to understand the connection between lineage state and expression of these sensors.

Overview Figure

We have found that the cGAS-STING pathway, which is required for systemic anti-tumor immune responses to local radiation, is inactive in neuroblastoma. Our work will determine how pathway restoration impacts therapy responses.

We have identified small molecules that activate NF-kappaB signaling in selective neuroblastoma cell lines and are working to understand their selectivity and their impact on immunotherapy responses.