Thomas G. Boyer, PhD

The unifying theme of our research program is to understand the function and regulation of the multiprotein Mediator of transcription, and further clarify how Mediator dysfunction as a consequence of mutation or misexpression of its constituent subunits contributes to human disease. Mediator is a conserved multisubunit signal-processor through which regulatory information conveyed by gene-specific transcription factors is transduced to RNA polymerase II. In this capacity, Mediator serves to channel regulatory signals from activator and repressor proteins to affect changes in gene expression programs that control diverse physiological processes, including cell growth and homeostasis, development, and differentiation. Structurally, Mediator is assembled from a set of 26 core subunits into three distinct modules termed “head”, “middle”, and “tail” that bind tightly to RNA Polymerase II. MED12, along with MED13, CDK8, and Cyclin C (CycC), comprise a fourth “kinase” module that resides in variable association with core Mediator. Notably, we and others have shown that Mediator kinase activity is required for nuclear transduction of signals instigated by multiple developmental and oncogenic pathways. Our primary research interest over the past several years has centered on the Mediator kinase module and its role as an endpoint in these fate-determining signal transduction pathways. In this regard, we aim understand how physiological cell signals that converge on the kinase module in Mediator inform proper development of the brain, uterus, prostate, and intestine. Further,  we seek to clarify how pathological dysregulation of these signals elicits X-linked intellectual disability and neurodegenerative disease, uterine leiomyomas, and prostate and colorectal cancers. We expect these studies to reveal important mechanistic insight concerning the function of Mediator in developmental gene control that might be leveraged to advantage in the development of molecularly targeted therapies across a range of human pathologies.

Related Diseases: Uterine leiomyomas, Colorectal and Prostate Cancers, X-linked intellectual disability and Alzheimer’s disease.

Techniques: Biochemistry, Molecular/Cell biology, human stem cell- and animal-based models .