We are focussed on with new strategies for therapy aimed at chromosomal translocation gene products, like LMO2 and translocation protein fusions, and hard-to-drug proteins, like mutant RAS and MYC. We are developing technologies using intracellular antibodies with warheads (such as E3 ligase for protein degradation or pro-caspases for induced cell death) together with methods to allow systemic delivery of these protein macromolecules (designated macrodrugs). Our work has also recently shown that the binding sites of antibodies on target proteins can be used to select small molecule compounds that act as surrogates of the antibody for drug discovery.
Our approach is multi-disciplinary, integrating molecular biology, cell biology, antibody design, structural biology, and chemical biology. The long-term goal is creation of generic strategies for deploying intracellular antibodies are drugs per se and for using intracellular antibodies in small molecule drug discovery programmes. In particular, this work is aimed at allowing the many chromosomal translocation proteins, found in all cancers from leukaemia/lymphoma, sarcomas and carcinomas, to be used as drug targets in cancer treatment.
The LMO gene and protein family
Blog by Professor Terry Rabbitts on RAS-binding compounds
MRC Laboratory of Molecular Biology
Wikipedia article on Professor Terry Rabbitts