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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

Two human metabolites rescue a C. elegans model of Alzheimer's disease via a cytosolic unfolded protein response.
P Joshi, M Perni, R Limbocker, B Mannini, S Casford, S Chia, J Habchi, J Labbadia, CM Dobson, M Vendruscolo
– Commun Biol
(2021)
4,
843
Squalamine and Its Derivatives Modulate the Aggregation of Amyloid-β and α-Synuclein and Suppress the Toxicity of Their Oligomers
R Limbocker, R Staats, S Chia, FS Ruggeri, B Mannini, CK Xu, M Perni, R Cascella, A Bigi, LR Sasser, NR Block, AK Wright, RP Kreiser, ET Custy, G Meisl, S Errico, J Habchi, P Flagmeier, T Kartanas, JE Hollows, LT Nguyen, K LeForte, D Barbut, JR Kumita, C Cecchi, M Zasloff, TPJ Knowles, CM Dobson, F Chiti, M Vendruscolo
– Front Neurosci
(2021)
15,
680026
Quantifying misfolded protein oligomers as drug targets and biomarkers in Alzheimer and Parkinson diseases
K Kulenkampff, AM Wolf Perez, P Sormanni, J Habchi, M Vendruscolo
– Nature Reviews Chemistry
(2021)
5,
277
Infrared nanospectroscopy reveals the molecular interaction fingerprint of an aggregation inhibitor with single Aβ42 oligomers
FS Ruggeri, J Habchi, S Chia, RI Horne, M Vendruscolo, TPJ Knowles
– Nature Communications
(2021)
12,
688
Publisher Correction: A dopamine metabolite stabilizes neurotoxic amyloid-β oligomers.
R Cataldi, S Chia, K Pisani, FS Ruggeri, CK Xu, T Šneideris, M Perni, S Sarwat, P Joshi, JR Kumita, S Linse, J Habchi, TPJ Knowles, B Mannini, CM Dobson, M Vendruscolo
– Communications biology
(2021)
4,
154
A dopamine metabolite stabilizes neurotoxic amyloid-β oligomers.
R Cataldi, S Chia, K Pisani, FS Ruggeri, CK Xu, T Šneideris, M Perni, S Sarwat, P Joshi, JR Kumita, S Linse, J Habchi, TPJ Knowles, B Mannini, CM Dobson, M Vendruscolo
– Communications biology
(2021)
4,
19
Screening of small molecules using the inhibition of oligomer formation in α-synuclein aggregation as a selection parameter
R Staats, TCT Michaels, P Flagmeier, S Chia, RI Horne, J Habchi, S Linse, TPJ Knowles, CM Dobson, M Vendruscolo
– Communications Chemistry
(2020)
3,
191
Structural and dynamics analysis of intrinsically disordered proteins by high-speed atomic force microscopy.
N Kodera, D Noshiro, SK Dora, T Mori, J Habchi, D Blocquel, A Gruet, M Dosnon, E Salladini, C Bignon, Y Fujioka, T Oda, NN Noda, M Sato, M Lotti, M Mizuguchi, S Longhi, T Ando
– Nature Nanotechnology
(2020)
16,
181
Trodusquemine displaces protein misfolded oligomers from cell membranes and abrogates their cytotoxicity through a generic mechanism.
R Limbocker, B Mannini, FS Ruggeri, R Cascella, CK Xu, M Perni, S Chia, SW Chen, J Habchi, A Bigi, RP Kreiser, AK Wright, JA Albright, T Kartanas, JR Kumita, N Cremades, M Zasloff, C Cecchi, TPJ Knowles, F Chiti, M Vendruscolo, CM Dobson
– Communications Biology
(2020)
3,
435
Rationally designed antibodies as research tools to study the > structure-toxicity relationship of amyloid-b oligomers
R Limbocker, B Mannini, R Cataldi, S Chhangur, AK Wright, RP Kreiser, JA Albright, S Chia, J Habchi, P Sormanni, JR Kumita, FS Ruggeri, CM Dobson, F Chiti, FA Aprile, M Vendruscolo
– International Journal of Molecular Sciences
(2020)
21,
E4542
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Research Staff Scientist

Telephone number

01223 336427 (shared)

Email address