Professor of Molecular Biology
Our aims are to utilise molecular biology to establish new technologies to study and understand cancer. We are trying to define how chromosomal translocation genes affect proliferation and differentiation from cancer initiating cells (where translocations occur) to overt cancer and in epithelial cancers, to invasive disease. This work amalgamates technologies for creating in vivo models of chromosomal translocations that mark the cancer initiating cells with fluorescent protein expression and transcriptome analysis (concentrating on the surfaceome and transcription factor expression patterns) using deep sequencing RNA-seq to discover new potential therapy targets.
The second, allied aim of our work, involves establishing technologies to target protein function inside cells particularly protein-protein interactions, using antibody fragments as drug surrogates for functional ablation of target proteins (our intracellular immunotherapy programme). We are isolating small molecules and peptides that mirror the inhibitory properties of the antibody fragments and our goals are to develop laboratory reagents to study cancer development and drug-like molecules as leads for therapeutic application. Allied to these approaches, we are examining cell surface protein expression in primary tumours and metastatic disease to define cell interactions that potentiate cancer and identify molecules at the cell surface that could be used in therapy, such as conventional antibody-mediated cancer treatment.
Surfaceome interrogation using an RNA-seq approach highlights leukemia initiating cell biomarkers in an LMO2 T cell transgenic model.
Pais H. et al, (2019), Sci Rep, 9
Lipid-mRNA nanoparticle designed to enhance intracellular delivery mediated by shock waves.
Zhang J. et al, (2019), ACS Appl Mater Interfaces
Bioluminescence Resonance Energy Transfer 2 (BRET2)-Based RAS Biosensors to Characterize RAS Inhibitors.
Bery N. and Rabbitts TH., (2019), Curr Protoc Cell Biol
Structure-based development of new RAS-effector inhibitors from a combination of active and inactive RAS-binding compounds.
Cruz-Migoni A. et al, (2019), Proc Natl Acad Sci U S A, 116, 2545 - 2550
Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment.
Quevedo CE. et al, (2018), Nat Commun, 9