We are primarily interested in the role of Wnt mediated signal transduction and gene transcription in stem cells and in cancer. Our research hypothesis is that cell electrical potential is a key regulator of gene transcription. A translational objective is to convert the mechanistic knowledge about Wnt signalling into regenerative medicine and cancer therapies and biomarkers.
Wnts are conserved, cysteine-rich secreted protein ligands, acting as close-range signalling molecules. Wnt signal transduction pathway, with free intracellular calcium (Ca2+i) and β-catenin, a 92 kDa transcription factor co-activator as two key intracellular transducers, is critical in stem cell homeostasis and in diseases like cancers (e.g. colo-rectal, breast, prostate).
We have shown that Wnt ligands control cell membrane electrical potential (Ashmore, et al, 2019). This discovery of a novel mechanism of Wnt signal transduction underpins our approach towards identifying membrane potential regulating compounds (MPRCs) as inhibitors of Wnt signalling that could be developed as safe and cost-effective therapy for cancers.
We also employ quantitative expression of Wnt transcription targets in human tissue, combined artificial intelligence techniques, to develop robust biomarkers for diagnosis and prognostication of carcinomas and other rare diseases (Xie et al, 2023; Arthurs & Ahmed, 2022).
With colleagues interested in epidemiology and clinical trials, we are also interested in exploring avenues to translate our basic science for patient benefit, particularly in low and middle income countries (LMICs), using drug repurposing. Some MPRCs of interest are drugs that have been in clinical use for indications other than cancer; we aim to use a drug discovery platform combining wet lab and in vivo analysis of fundamental biological mechanisms through target validation to reprofiling MPRCs for cancer therapy. We are currently preparing for a first in man clinical trial for an MPRC as a therapy for rectal cancer. Our interest in developing therapies directed towards both the developed world and LMICs into examining electronic health records and addressing health care provision and policies (Ahmed & Williams, 2023).