Ciaran P Seath

Overview

The Seath Lab is interested in developing chemical biology approaches to understand how gene transcription is controlled in healthy and diseased settings and using this information to identify and validate new targets for drug discovery. To do this, we employ a multidisciplinary approach using a broad palette of techniques spanning from organic photochemistry, medicinal chemistry, chemoproteomics, and molecular and cellular biology.

Research Focus

Our research focus can be divided into three main areas. (1) Studying undruggable transcription factors in disease. (2) Understanding how chromatin structure impacts transcription. (3) The development of new chemical biology approaches to understand biomolecular interactions. 

1. Aberrant activation of gene transcription is the genesis of many human diseases including cancer. This process is controlled by a network of DNA binding proteins called transcription factors (TFs), which act in concert with nucleosomes, epigenetic readers, ncRNAs, and a host of other chromatin associated factors to regulate cellular RNA and protein concentrations. Our lab has developed tools to accurately map these interactions and understand how they change in disease, with his we have discovered a new cancer driving signaling pathway that is promoted by changes in protein localization rather than abundance. 
2. In addition to using studying factors that regulate transcription at the single protein level, we are also interested in studying how chromatin states regulate gene expression at the systems level, particularly in response to external stimuli. For example, many bioactive small molecules induce their effects through modulation of epigenetic states but in cases where defined mechanisms are unknown it can be challenging to predict cellular resistance or sensitivity, leading to clinical failures. We apply novel proteomics approaches to understand mechanisms of chromatin regulation, and how this can inform on resistance and sensitivity to modern therapeutics.
3. In pursuit of the above aims, our research team develops new chemical biology approaches to understand how biomolecules interact in complex environments such as primary cells and tissue samples. This involves the development on novel catalytic reactions that can function with perfect efficiency in the most complex of settings.