I obtained a PhD from the School of Pharmacy of Universite Rene Descartes in Paris, France, in a medicinal chemistry laboratory. I then undertook a postdoctoral training in the Pharmacology Department of the University of California San Diego (UCSD), where I developed skills in Biochemistry and Cell biology, with the idea of better understanding the drug targets. I combined my knowledge of chemistry and biology to conduct a drug discovery...view more
I obtained a PhD from the School of Pharmacy of Universite Rene Descartes in Paris, France, in a medicinal chemistry laboratory. I then undertook a postdoctoral training in the Pharmacology Department of the University of California San Diego (UCSD), where I developed skills in Biochemistry and Cell biology, with the idea of better understanding the drug targets. I combined my knowledge of chemistry and biology to conduct a drug discovery campaign that led to the identification of first-in-class inhibitors of the phosphatase PHLPP. Upon moving to Australia, in the Institute for Molecular Biology (IMB) at University of Queensland (UQ), I became interested in protein-protein interactions and developed the platform of assays to interrogate protein-protein interactions that is now at the heart of our work in the laboratory. Since joining UNSW in 2015, my group has worked on protein aggregation in neurodegenerative diseases and drug ability of transcription factors. My work is now focusing on understanding how protein-protein interactions are affected during pathological processes. The main axes of the laboratory are the study of the processes of protein aggregation and the development of a diagnostic test of Parkinson’s disease .
My Research Activities
The role of a protein can be profoundly affected by its protein partners. Specific interactions can select outputs when a protein serves as hub between different pathways or serve as a switch between on and off forms. Because of this crucial role, loss or gain of interactions play an important role in disease. In my laboratory, we are particularly interested in neurodegenerative diseases and in studying the aggregation processes in Parkinson’s disease .
α-synuclein aggregation & diagnostics of Parkinson’s disease and other synucleinopathies
Neurodegenerative diseases such as Parkinson’s disease (PD) are a prime example of gains of interactions leading to pathologies. α-Synuclein (Syn) aggregation is a hallmark of PD and other related disorders (such as multiple system atrophy (MSA) or dementia with Lewy Bodies (DLB)), called synucleinopathies. Syn aggregation is a promising biomarker for early detection and assessment of disease progression. It was recently shown that Syn seeds could be detected and amplified from biological fluids, allowing to discriminate PD patients even at a prodromal phase. We showed interactions with other proteins could modulate Syn aggregation. First, we examined the effect of pathological mutants, linked to early-onset PD, on aggregation propensity. These mutants had an increased tendency to aggregates compared to wild type. Some mutants did not co-aggregate with WT Syn suggesting a structural imprinting by the mutations (Sci Rep 2016). We demonstrated that β-synuclein (IJMS 2018) and Munc18 (J.Cell.Bio 2016) prevented Syn aggregation, acting as molecular chaperones. The study was extended to other proteins partners found in the neuronal protein inclusions. We observed that self-association drove partner selectivity with some proteins recognizing the oligomeric but not fibrillar form of Syn (Comms Bio, under revision).