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Welcome to the Mabe lab in the College of Pharmacy and Institute for Cancer Research at Purdue University. The goal of our lab is to make strides in improving outcomes for children with cancer. Recent efforts have identified the kinase VRK1 as a synthetic lethal target in pediatric tumors arising from neural tissue. We are working with chemists to develop VRK1-selective inhibitors and identify strategies to best utilize translate inhibitors into the clinic. In addition, we discovered new epigenetic targets that regulate expression of the antigen GD2 in multiple solid tumor contexts. These targets will help guide combination therapies that enhance therapeutic response to GD2-targeted immunotherapies.

Pediatric Oncology

Our research program integrates genome-wide CRISPR/Cas9 screening platforms with sequencing technologies to  prioritize new drug targets and combinatorial therapies  in pediatric solid tumors.

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Research Vision

Epigenetic dysregulation is frequently observed in the disease pathology of pediatric cancers. This is due to the disruption of tightly controlled developmental pathways during early childhood, which are regulated by transcription factors and epigenetic modifying complexes. It is becoming increasingly recognized that pediatric tumors harbor intrinsic epigenetic plasticity that enables tumor cells to rapidly transition between lineage states to overcome extrinsic and intrinsic stressors. As such, a mechanistic understanding of the epigenetic and transcriptional pathways mediating this plasticity is essential to ascertain how tumors resist cytotoxic, targeted, differentiation, and immunotherapies. The focus of my lab is to understand how epigenetic reprogramming contributes to resistance to therapy, and how we can selectively target these pathways to prevent tumor relapse. This framework will inform how we can better target cell state transition with small molecule and immune-based therapeutics in the clinic. ​

Recent news & publications

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Transition to a mesenchymal state in neuroblastoma confers resistance to anti-GD2 antibody via reduced expression of ST8SIA1

Mabe NW, Huang M, et. al. discover that the immunotherapy target GD2 is downregulated by transition to a mesenchymal state and is reversible with EZH2 inhibitors.

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VRK1 as a synthetic lethal target in VRK2 promoter–methylated cancers of the nervous system

So J, Mabe NW, Englinger B et. al. discover that cancers from a neural lineage lowly express VRK2, thus rendering them sensitive to knockout of the paralog VRK1 kinase.

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K99/R00 awarded!

Nathaniel Mabe receives K99/R00 funding to evaluate the role of the PRC1 complex in cell state and anti-GD2 therapy in neuroblastoma.

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