Professor Laura Itzhaki

Tandem-repeat proteins: Folding, function, role in disease and therapeutic intervention

Professor of Structural Pharmacology

Head of the Department

Member of:

E-mail: lsi10 [at] cam.ac.uk

Tel: +44 (0)1223 334017

Fax: +44 (0)1223 334100

Keywords

Tandem-repeat proteins, protein engineering, protein folding, protein design, protein-protein interactions, molecular therapeutics, targeted protein degradation, biomolecular condensates

Investigator biography

Laura did her PhD with Dr Phil Evans, Department of Biochemistry, Cambridge, and then moved to a postdoc in the Department of Chemistry with Prof. Sir Alan Fersht. She subsequently held a Beit Memorial Fellowship in Medical Research and then an MRC Career Development Award, with which she started her own group.

In 2003 she moved to the MRC Cancer Cell Unit in Cambridge and briefly returned to the the Department of Chemistry, before taking up a Lectureship in the Department of Pharmacology in 2013. Laura is co-Director of Cambridge Academy of Therapeutics Sciences. In October 2020 she became Head of Department of Pharmacology.

Research summary

Our research focuses on a class of proteins with very distinctive architectures, known as tandem-repeat proteins. Our group and others have shown that the simple modular, one-dimensional architecture of tandem-repeat proteins gives them distinctive properties that make it uniquely straightforward to map the energetics of their structures and to rationally redesign their stability, folding and binding function.

This class of proteins is thus an exceptionally sensitive and versatile tool that we are now exploiting to dissect otherwise intractable cellular mechanisms. We are also exploring how to exploit the extraordinary design-ability of these proteins for biomedical and biotechnology applications.

Lab Members

Dr Pam Rowling,Dr Boguslawa Korona, Dr Maria Zacharopoulou, Dr Andrew Baker, Dr Laura Blenkarn, Dr Gabriela Guedes, Dr Giovanna Zinzalla, Dr Mark Mycroft, Mateo Hoare, Adrian Ho, Yawei Qi, Marco Tsang, Ying Kok, Chloe Burgess, Nora Haanaes, Khushboo Matwani, Connor MacFarlane

Selected recent publications

Naqvi M., M. et al., Itzhaki L., S. Small Molecule Activators of Protein Phosphatase 2A Exert Global Stabilizing Effects on the Scaffold PR65. JACS Au (2026). 10.1021/jacsau.6c00003
Korona B. et al., Itzhaki L., S. Coiled-coil scaffolds for targeted protein degradation. bioRxiv, 2025. 10.64898/2025.12.22.695764 3.Mylemans B. et al., Itzhaki L. S., Woolfson, D. N. De novo designed bifunctional proteins for targeted protein degradation. bioRxiv, 2025. 10.64898/2025.12.22.695915
Baker A. G., Ho A., P. T., Itzhaki L.,S., Fruk L. Nanoparticle-Mediated Targeted Protein Degradation: An Emerging Therapeutics Technology. Angew Chem Int Ed Engl. 2025. doi: 10.1002/anie.202503958
Burbidge O., M. W. Pastok, S. L. Hodder, G. Zenkevičiūtė, M. E. M. Noble, J. A. Endicott, and L. S. Itzhaki. Nanobodies restore stability to cancer-associated mutants of tumor suppressor protein p16INK4a. Structure (2025). 10.1016/j.str.2025.07.017
Eapen R. et al., Itzhaki L., S. Development of D-box peptides to inhibit the Anaphase Promoting Complex/Cyclosome. eLife, 2025. doi: 10.7554/eLife.104238.2
Synakewicz M., R. S. Eapen, A. Perez-Riba, P. J. E. Rowling, D. Bauer, A. Weißl, G. Fischer, M. Hyvönen, M. Rief, L. S. Itzhaki, and J. Stigler. Unraveling the mechanics of a repeat-protein nanospring: from folding of individual repeats to fluctuations of the superhelix. ACS Nano, 16(3): 3895-3905, 2022.
Ripka J. F., A. Perez-Riba, P. K. Chaturbedy, and L. S. Itzhaki. Testing the length limit of loop grafting in a helical repeat protein. Curr. Res. Struct. Biol., 3(1): 30-40, 2021.
Smith B. M., P. J. E. Rowling, C. M. Dobson, and L. S. Itzhaki. Parallel and sequential pathways of molecular recognition of a tandem-repeat protein and its intrinsically disordered binding partner. Biomolecules, 11(6):827, 2021.
Diamante, A., P. Chaturbedy, P. Rowling, J. Kumita, R. S. Eapen, S. H. McLaughlin, M. de la Roche, A. Perez-Riba, and L. S. Itzhaki. Engineering mono- and multi-valent inhibitors on a modular scaffold. Chem. Sci., 12(3):880-895, 2021. doi: 10.1039/D0SC03175E
Perez-Riba, A., E. Komives, E. R. G. Main and L. S. Itzhaki. Decoupling a tandem-repeat protein: Impact of multiple loop insertions on a modular scaffold. Sci. Rep., 9:15439, 2019.
Perez-Riba, A., A. R. Lowe, E. R. G. Main, and L. S. Itzhaki. Context-dependent energetics of loop extensions in a family of tandem-repeat proteins. Biophys. J., 114(11):2552-2562, 2018.
Perez-Riba, A., M. Synakewicz, and L. S. Itzhaki. Opinion piece: Folding cooperativity and allosteric function in the tandem-repeat protein class. Phil. Trans. R. Soc. B, 373:20170188, 2018.
Xu, W., Y. Heng Lau, G. Fischer, Y. S. Tan, A. Chattopadhyay, M. de la Roche, M. Hyvönen, C. S. Verma, D. R. Spring, and L. S. Itzhaki. Macrocyclized extended peptide Inhibiting the substrate-recognition domain of tankyrase. J. Am. Chem. Soc., 139(1):2245-2256, 2017.