The lab uses genetically engineered mouse models of cancer (GEMMs) to precisely control the genetics and tissue of origin of cancer development in the mouse. Prior work has demonstrated that these models exhibit very few additional somatic mutations compared to many human cancers.

From these models, we develop high-throughput chemical screens to identify small molecules to selectively target cancer based on driver mutation specificity and lineage of origin. Small molecule ‘hits’ from these screens are extensively validated against murine and human cancer cell lines, and in vivo using transplantation models and autochthonous GEMMs. Biochemical and genetic studies of these small molecules are pursued to identify the chemical target and mechanism of action.

We also study well-characterized cancer cell lines derived from pediatric sarcomas, including Ewing sarcoma and synovial sarcoma. These cancers are driven by unique translocations that encode neomorphic oncogenic transcriptional regulators.

The molecular mechanisms by which these fusions initiate tumorigenesis remain incompletely defined, and therefore no targeted therapies exist for these malignancies. The McFadden lab is pursuing high-throughput screens to identify new entry points for impairing the oncogenic action of these fusions.

Active Projects

  • Identifying selective toxins for small cell lung cancer
  • Targeting the “untargetable”: Ewing sarcoma
  • Re-differentiation of radioiodine-resistant thyroid carcinoma

Current Funding

Prior Funding