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Centre for Misfolding Diseases

Dr Johnny Habchi

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

Trodusquemine enhances A beta(42) aggregation but suppresses its toxicity by displacing oligomers from cell membranes
R Limbocker, S Chia, FS Ruggeri, M Perni, R Cascella, GT Heller, G Meisl, B Mannini, J Habchi, TCT Michaels, PK Challa, M Ahn, ST Casford, N Fernando, CK Xu, ND Kloss, SIA Cohen, JR Kumita, C Cecchi, M Zasloff, S Linse, TPJ Knowles, F Chiti, M Vendruscolo, CM Dobson
– Nature Communications
(2019)
10,
225
Chemical and mechanistic analysis of photodynamic inhibition of Alzheimer's beta-amyloid aggregation
M Ahn, BI Lee, S Chia, J Habchi, JR Kumita, M Vendruscolo, CM Dobson, CB Park
– Chem Commun (Camb)
(2019)
55,
1152
Stabilization and characterization of cytotoxic Aβ40 oligomers isolated from an aggregation reaction in the presence of Zinc ions
B Mannini, J Habchi, S Chia, FS Ruggeri, M Perni, TPJ Knowles, CM Dobson, M Vendruscolo
– ACS chemical neuroscience
(2018)
9,
2959
SAR by kinetics for drug discovery in protein misfolding diseases
S Chia, J Habchi, TCT Michaels, SIA Cohen, S Linse, CM Dobson, TPJ Knowles, M Vendruscolo
– Proceedings of the National Academy of Sciences
(2018)
115,
10245
Microfluidic deposition for resolving single-molecule protein architecture and heterogeneity
FS Ruggeri, J Charmet, T Kartanas, Q Peter, S Chia, J Habchi, CM Dobson, M Vendruscolo, TPJ Knowles
– Nature communications
(2018)
9,
3890
Structure-based design of allosteric calpain-1 inhibitors populating a novel bioactivity space
L Kalash, J Cresser-Brown, J Habchi, C Morgan, DJ Miller, RC Glen, RK Allemann, A Bender
– European journal of medicinal chemistry
(2018)
157,
1264
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
– Journal of Neuroscience 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
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
– Biophys J
(2017)
113,
2723
Monomeric and fibrillar alpha-synuclein exert opposite effects on the catalytic cycle that promotes the proliferation of A beta 42 aggregates
S Chia, P Flagmeier, J Habchi, V Lattanzi, S Linse, CM Dobson, TPJ Knowles, M Vendruscolo
– Proceedings of the National Academy of Sciences of the United States of America
(2017)
114,
8005
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Research Staff Scientists

Telephone number

01223 336427 (shared)

Email address