Development of Pharmacological Probes for Road-Mapping WD40 Domain Proteins
Since the dawn of the human genome sequencing in 2003, great hopes have been put into the development of new therapeutics and personalized medicine tailored on individual DNA profiles. Nonetheless, progress in these fields has been slow, mainly due to the focus of the research community on only a small number of genes and proteins involved in diseases. As a result, there remains a plethora of unexplored proteins and genes responsible for diseases such as Alzheimer's, cancer, or rare/orphan diseases, that have yet to be understood. To further the knowledge in the field of disease therapeutics, a more in-depth understanding of these unexplored proteins is necessary. This project will focus on developing chemical probes for WD40 Repeat (WDR) proteins, a protein family that is largely unexplored, despite its abundance in the human body and its involvement in diseases such as cancer. WDRs are ubiquitous in eukaryotes, and are involved in processes like signal transduction to apoptosis. While it has recently been shown that WDRs are in fact druggable targets, they are virtually entirely uncharted in drug discovery. Our goal is to develop chemical probes that can shed light on WDR function in cancer.