A major research focus is the regulatory mechanisms of aberrant RNA processing in cancer, particularly the regulation of alternative pre-mRNA splicing and processing, and miRNA biogenesis. One program studies the properties of Cyclin Dependent Kinase 12 (CDK12) in breast, ovarian, and prostate cancers. CDK12 interacts with spliceosomal proteins, RNA Pol2, and RNA processing factors to coordinately regulate transcription elongation and termination, poly-adenylation, and spliceosome activity. Using global quantitative mass spectrometry and RNA-seq methods in CRISPR/Cas9 engineered isogenic cancer cell line models the roles and mechanisms of CDK12 in regulating RNA processing are studied. Using small molecule inhibitors of CDK12 kinase activity the biological functions of CDK12 and its direct cellular targets are probed. A second program studies the oncogenic mechanisms of somatic mutations in the miRNA processing enzyme DICER1 in a broad spectrum of rare developmental cancers. The mutations affect only the RNase IIIb subdomain of DICER1 to abolish expression of 5P miRNAs. Isogenic cell lines and engineered mouse models are used to study mutant Dicer function.