Laboratory of X-Ray Protein Crystallography: Nuclear Receptors, Microbial Enzymology, and Broad-Based Cancer Therapeutics
Dr John B. Bruning
Understanding human disease requires knowledge of the structure-function relationships in protein sensor modulation.
This knowledge is incomplete on a broad spectrum of biological systems including nuclear receptor (NR) signalling, proteins involved in cancer biology, and pathogen protein machinery. Our research is focused on understanding these classes of protein interactions on an atomic level. In addition to gaining a basic understanding of protein mechanism, we also focus on structure guided drug design.
In our work in understanding NR signalling, we have uncovered new paradigms in NR allostery. These allosteric modulations can now be further studied on a broader scale and harnessed to employ structure guided drug design.
Work in the tuberculosis (TB) structural biology consortium has led to a quantum leap in understanding enzymology of the pathogen allowing for new chemotherapy development. We wish to use similar methodology to study a fungal pathogen for the discovery of new anti-fungal molecules.
Our research with proteins of the human replication fork, such as PCNA (Proliferating Cellular Nuclear Antigen) has uncovered atomic determinants of these protein modulators that can be used as new paradigms for cancer therapeutic targeting. We will continue this research to aid in the discovery of alternative cancer therapeutic targets and seek to understand their structure-function relationship.