Dr. Stegmaier’s laboratory focuses on the discovery of new cancer targets and small molecule therapeutic leads with the mission of translating laboratory findings to the clinic. In particular, her laboratory applies new chemical genomic approaches to the discovery of small molecule modulators of cancer, compounds that serve as tools in the laboratory to identify new cancer targets and as leads for molecularly informed drug discovery. In order to overcome the limitations to traditional target and phenotype-based screening, Dr. Stegmaier and her colleagues developed a chemical genomic approach to screening, gene expression-based high-throughput screening (GE-HTS), in which a gene expression signature serves as a surrogate for different biological states. The initial proof of principle experiments successfully applied this approach to the identification of inducers of acute myeloblastic leukemia (AML) differentiation. Because the GE-HTS platform is an entirely generic system, it can be applied to a multitude of small molecule library screens. Cancer discovery efforts in the laboratory are focused on the alteration of the malignant state (e.g. differentiation) and the modulation of “undruggable” oncoproteins (e.g. transcription factors). The laboratory exploits confirmed hits as tool compounds to explore mechanisms of oncogenesis using a variety of approaches: genomic, RNA interference, pharmacologic, and proteomic. The most ambitious goal is the translation of confirmed hits to clinical trial. Clinical trials for AML and Ewing sarcoma have resulted from this research.