Laura S. Itzhaki

A generalizable method for the purification and biophysical characterization of bacterial membrane receptors.

Programmable DNA-peptide nanostructures for multivalent regulation of intracellular signalling

Abstract PR010: Targeted degradation of cyclin T1 constrains transcription elongation and triggers tumour cell apoptosis

Transcriptional dysregulation is a hallmark of cancer and is frequently driven by oncogenic alterations that rewire downstream gene-expression programmes. Although kinase inhibitors targeting upstream oncogenic drivers can produce clinical benefit, responses are often limited by acquired resistance and pathway adapta...

Combinatorial screening of biological degrader modules identifies heterobifunctional molecules that efficiently destroy MYC, leading to rapid tumour cell death in vitro and in vivo

Targeted protein degradation is a potent strategy against intracellular proteins impervious to traditional drugs. We describe a platform reliant on high-throughput cloning and mRNA-based delivery to quickly screen 100s-1000s of modular biological degraders, which we challenge against the high-turnover c-Myc oncoprotein...

Abstract A049: Rational grafting of p53TAD onto CTPR scaffolds generates potent p53-MDM2 antagonists Yawei Qi1, Albert Perez-Riba1, Laura S. Itzhaki11Department of Pharmacology, University of Cambridge, Cambridge, UK

Rational grafting of p53TAD onto CTPR scaffolds generates potent p53-MDM2 antagonists and establishes CTPR proteins as highly engineerable scaffolds for peptide-motif grafting and expand the toolkit of protein-based antagonists for targeting oncogenic protein–protein interactions, potentially opening up new therapeutic...

A generalisable method for the purification and biophysical characterisation of bacterial membrane receptors

A generalizable workflow for producing soluble receptor domains from membrane proteins is established and validated HasR constructs suitable for downstream ligand-screening applications, including aptamer and nanobody discovery.

Abstract B045: Targeted degradation of cyclin T1 constrains transcription elongation and triggers tumour cell apoptosis

It is demonstrated that selective degradation of CCNT1 can effectively collapse pTEFb-dependent transcriptional programmes and compromise tumour cell fitness, which may offer a more selective and durable route for therapeutic intervention in transcriptionally dependent tumours.