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


Prof. Laura Itzhaki - Group Leader

Newnham College

Member of the Naked Mole-Rat Initiative


Tel:+44 1223 334017

Fax:+44 1223 334100


Tandem-repeat proteins, protein engineering, protein folding, protein design, protein-protein interactions, cancer therapeutics

Investigator biography

Laura did her Ph.D. 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, Cambridge and briefly returned to the the Department of Chemistry before taking up a Lectureship in the Department of Pharmacology in 2013.


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 compared with globular proteins and makes it uniquely straightforward to map the energetics of their structures and to rationally redesign their stability, folding and molecular recognition. 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 focusing on ankyrin, HEAT and ARM repeat proteins that play important roles in disease, in particular cancer, and we are using the insights we obtain to develop therapeutic strategies for targeting them; we are also exploring how to exploit the extraordinary design-ability of these proteins for biomedical and biotechnology applications.


Lab Members

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Key publications

Tsytlonok, M., S. M. Ibrahim, P. Rowling, W. Xu, M. J. Ruedas-Rama, A. Orte, D. Klenerman, and L. Itzhaki. Single-molecule FRET reveals hidden complexity in a protein energy landscape. Structure, 23(1): 190 – 198 (2015).

Rowling, P.J.E., Cook, R., Itzhaki, L.S. Towards classification of BRCA1 missense variants using a biophysical approach.  J. Biol. Chem. 285: 20080-7 (2010).

Werbeck, N.D., Rowling, P.J., Chellamuthu, V.R., Itzhaki, L.S.  Shifting transition states in the unfolding of a large ankyrin repeat protein.  Proc. Natl. Acad. Sci. USA 105: 9982-7 (2008).

Lowe, A.R., Itzhaki, L.S.  Rational redesign of the folding pathway of a modular protein.  Proc. Natl. Acad. Sci. USA 104: 2679-84 (2007).