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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

Massively parallel C. elegans tracking provides multi-dimensional fingerprints for phenotypic discovery.
M Perni, PK Challa, JB Kirkegaard, R Limbocker, M Koopman, MC Hardenberg, P Sormanni, T Müller, KL Saar, LWY Roode, J Habchi, G Vecchi, N Fernando, S Casford, EAA Nollen, M Vendruscolo, CM Dobson, TPJ Knowles
– J Neurosci Methods
(2018)
306,
57
Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes
J Habchi, S Chia, C Galvagnion, TCT Michaels, MMJ Bellaiche, FS Ruggeri, M Sanguanini, I Idini, JR Kumita, E Sparr, S Linse, CM Dobson, TPJ Knowles, M Vendruscolo
– Nature chemistry
(2018)
10,
673
Chemical Kinetics for Bridging Molecular Mechanisms and Macroscopic Measurements of Amyloid Fibril Formation
TCT Michaels, A Šarić, J Habchi, S Chia, G Meisl, M Vendruscolo, CM Dobson, TPJ Knowles
– ANNUAL REVIEW OF PHYSICAL CHEMISTRY, VOL 69
(2018)
69,
1
Probing the Interaction of ABETA42 Amyloid Species with an Aggregation Suppressor Molecule by Infrared Nanospectroscopy
FS Ruggeri, J Habchi, S Chia, M Vendruscolo, TPJ Knowles
– Biophysical Journal
(2018)
114,
224a
Modulating Amyloid-Beta Aggregation to Reduce the Toxicity of its Oligomeric Aggregates
R Limbocker, B Mannini, S Chia, FS Ruggeri, M Perni, R Cascella, C Xu, J Habchi, JR Kumita, F Chiti, TPJ Knowles, M Vendruscolo, CM Dobson
– Biophysical Journal
(2018)
114,
430A
Systematic Development of Small Molecules to Inhibit Specific Microscopic Steps of Amyloid-Beta42 Aggregation in Alzheimer's Disease
S Chia, J Habchi, R Limbocker, B Mannini, M Ahn, M Perni, O Hansson, P Arosio, JR Kumita, PK Challa, SIA Cohen, S Linse, CM Dobson, TPJ Knowles, M Vendruscolo
– Biophysical Journal
(2018)
114,
225a
Interfacial Properties of NTAIL, an Intrinsically Disordered Protein.
A Bénarouche, J Habchi, A Cagna, O Maniti, A Girard-Egrot, J-F Cavalier, S Longhi, F Carrière
– Biophysical Journal
(2017)
113,
2723
Monomeric and fibrillar α-synuclein exert opposite effects on the catalytic cycle that promotes the proliferation of Aβ42 aggregates.
S Chia, P Flagmeier, J Habchi, V Lattanzi, S Linse, CM Dobson, TPJ Knowles, M Vendruscolo
– Proc Natl Acad Sci U S A
(2017)
114,
8005
Attenuating the Toxicity of Amyloid-Beta Aggregation with Specific Species
R Limbocker, B Mannini, M Perni, S Chia, G Heller, FS Ruggeri, J Habchi, G Meisl, PK Challa, M Zasloff, TPJ Knowles, M Vendruscolo, CM Dobson
– Biophysical Journal
(2017)
112,
494a
Single amyloid aggregates chemical and structural analysis by infrared nanospectroscopy
FS Ruggeri, J Habchi, C Sean, M Vendruscolo, TPJ Knowles
– EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2017)
46,
S370
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Research Staff Scientist

Telephone number

01223 336427 (shared)