Our interdisciplinary research is aimed at understanding the basis of human disease and discovering and advancing new small molecule treatments.
Mediator-associated kinases CDK8 and CDK19 in Cancer and Disease
CDK8 and CDK19 associate with the Mediator, a large protein complex that spans enhancer-associated transcription factors and general transcriptional machinery. We synthesized the natural product cortistatin A, a highly specific and potent inhibitor of CDK8 and CDK19, and used it to probe the role of these kinases in regulating transcription and in cancer. We have found that inhibiting these kinase increases transcription of cell identity genes that can be repressed in acute myeloid leukemia and CDK8/19 inhibition is a therapeutic approach to this disease.
We are studying the mechanism by which these kinase regulate gene expression and are advancing CDK8/19 inhibitors towards human clinical trials.