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Centre for Misfolding Diseases

Educational background

I completed my BSc in Biochemistry at the Lebanese University during which I became interested in understanding the protein folding process. In order to pursue my interests, I joined an MSc programme in Aix-Marseille University, France, where I studied the folding of unstructured proteins, namely intrinsically disordered proteins.

My research during my MSc and PhD was centred on understanding the molecular mechanisms by which the folding of disordered proteins upon binding to their partners results in the gain of a function, which leads in some cases to human diseases. In particular, I studied the role of intrinsically disordered proteins in orchestrating the replicative machinery of RNA virsues.

Current research

After my PhD, I joined the Centre for Misfolding Diseases, where my research to date mainly focuses on the generation of new methods that allow the detailed understanding of the molecular principles underlying the misfolding of intrinsically disordered proteins, a hallmark of many diseases, such as Alzheimer’s and Parkinson’s diseases, for the aim of drug discovery.

At the Centre, I have worked on elucidating the fundamental principles of protein aggregation and on developing quantitative tools for the assessment of the efficacy of drug molecules in modulating the protein aggregation process. In collaboration with many colleagues and based on the accumulated knowledge in the Centre, we have set up an innovative and interdisciplinary drug discovery programme that aims at the selective targeting of specific microscopic processes in a controlled intervention during the aggregation of proteins associated with misfolding diseases, in particular Alzheimer’s and Parkinson’s diseases. A direct consequence of this endeavour was the ability to reach, for the first time, a detailed understanding of the mode of action of drug molecules on single microscopic steps during the aggregation process.

Research translation

This contribution has led to the translation of the drug discovery programme into practice by creating Wren Therapeutics, a biopharmaceutical company, in which I am currently the Head of R&D. Wren Therapeutics aims at bridging the gap between fundamental and translational research in order to generate transformative treatments across a wide range of protein misfolding diseases.

Publications

Extracting structural information from charge-state distributions of intrinsically disordered proteins by non-denaturing electrospray-ionization mass spectrometry.
L Testa, S Brocca, C Santambrogio, A D'Urzo, J Habchi, S Longhi, VN Uversky, R Grandori
– Intrinsically Disordered Proteins
(2014)
1,
e25068
Impact of crystal packing on coiled-coil flexibility.
F Ferron, D Blocquel, J Habchi, E Durand, M Sevajol, J Erales, N Papageorgiou, S Longhi
– Acta Crystallographica Section A: Foundations and advances
(2014)
70,
c1599
Coiled-coil deformations in crystal structures: the measles virus phosphoprotein multimerization domain as an illustrative example
D Blocquel, J Habchi, E Durand, M Sevajol, F Ferron, J Erales, N Papageorgiou, S Longhi
– Acta Crystallographica Section D, Structural Biology
(2014)
70,
1589
Structural disorder in viral proteins.
B Xue, D Blocquel, J Habchi, AV Uversky, L Kurgan, VN Uversky, S Longhi
– Chemical Reviews
(2014)
114,
6880
Introducing Protein Intrinsic Disorder
J Habchi, P Tompa, S Longhi, VN Uversky
– Chem Rev
(2014)
114,
6561
Diversification of EPR signatures in Site Directed Spin Labeling using a β-phosphorylated nitroxide.
N Le Breton, M Martinho, K Kabytaev, J Topin, E Mileo, D Blocquel, J Habchi, S Longhi, A Rockenbauer, J Golebiowski, B Guigliarelli, SRA Marque, V Belle
– Phys Chem Chem Phys
(2014)
16,
4202
Coiled-coil deformations in crystal structures: The measles virus phosphoprotein multimerization domain as an illustrative example
D Blocquel, J Habchi, E Durand, M Sevajol, F Ferron, J Erales, N Papageorgiou, S Longhi
– Acta Crystallographica Section D: Biological Crystallography
(2014)
70,
1589
Structural and Mechanistic Analyses of the Effects of Small Compounds on Amyloid Beta Self-Assembly
J Habchi, P Joshi, A Spilotros, D Svergun, M Vendruscolo
– BIOPHYSICAL JOURNAL
(2014)
106,
268A
Atomic resolution description of the interaction between the nucleoprotein and phosphoprotein of Hendra virus.
G Communie, J Habchi, F Yabukarski, D Blocquel, R Schneider, N Tarbouriech, N Papageorgiou, RWH Ruigrok, M Jamin, MR Jensen, S Longhi, M Blackledge
– PLoS pathogens
(2013)
9,
e1003631
Mapping induced folding of viral nucleoproteins using SDSL combined with EPR spectroscopy
M Martinho, L Nesme, A Fournel, Z El Habre, J Habchi, S Longhi, B Guigliarelli, V Belle
– EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2013)
42,
S67
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Research Staff Scientist

Telephone number

01223 336427 (shared)

Email address