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.
Cloning, purification and structure determination of the HIV integrase-binding domain of lens epithelium-derived growth factor.
Hannon C. et al, (2018), Acta Crystallogr F Struct Biol Commun, 74, 143 - 149
The selection of single-domain antibody fragments (iDAbs) by intracellular antibody capture in yeast
rabbitts T. et al, (2018), Protocol Exchange
Intracellular immunization against HIV infection with an intracellular antibody that mimics HIV integrase binding to the cellular LEDGF protein.
Bao L. et al, (2017), Sci Rep, 7
Structural and functional characterization of a DARPin which inhibits Ras nucleotide exchange.
Guillard S. et al, (2017), Nat Commun, 8
Abstract LB-068: From intracellular antibody fragments to small molecule inhibitors of mutant KRAS
Quevedo CE. et al, (2017), Cancer Research, 77, LB-068 - LB-068