Translational disease models and neurodegeneration

We are interested in the enigmatic phenomena of protein misfolding, aggregation, and the intriguing prion-like spread of misfolded protein aggregates that characterizes these disorders in tauopathies and synucleinopathies. Our goal? To illuminate new avenues for precisely targeted therapies, striving to halt or mitigate the progression of these devastating conditions. 

Further, we're passionate about cutting-edge cellular models that faithfully mimic human diseases. Why? Because our ultimate goal is to bridge the gap between fundamental research and clinical success, and these models are our vital bridges. The future of translational disease models holds limitless promise. CRISPR-Cas9 genome editing, induced pluripotent stem cells (iPSCs), and AI-driven drug discovery are reshaping our approach to neurodegenerative diseases and other human diseases. 

The projects described below cover a wide range of scientific activities currently ongoing within the research group and laboratory of experimental medicine in general. 

1/ Structural and Biochemical Characterization of Tau and Alpha-Synuclein in Tauopathies and Synucleinopathies:

• Detailed analysis of the structure and biochemical properties of these proteins implicated in Alzheimer's disease (tau) and Parkinson's disease (alpha-synuclein).

2/ Effects of Tau Mutations on VQIVYK-Targeting Agents in Neurodegenerative Diseases:

• Examining how specific mutations in the tau repeat domain affect the efficacy of agents designed to target the repeat domain and reduce tau aggregation.

3/ Identification of Pharmacological Modulators of Tau Spreading in Alzheimer's Disease:

• With the goal of developing potential treatments, we aim to identify drugs that can target the spread of tau pathology.

4/ Identifying druggable targets conferring selective advantages to protein misfolding and aggregation (e.g., Tau Aggregation):

• The focus here is on discovering molecular targets within the pathways associated with protein misfolding and aggregation, particularly in the context of tau aggregation that contributes to selective vulnerability in tauopathies. These targets may be amenable to therapeutic intervention to prevent or reduce protein aggregation.

5/ Systems Approach to Understanding Aging and Neurodegeneration:

• This approach involves studying the complex interplay of biological systems, including genetics, molecular pathways, and environmental factors, to gain insights into the processes of ageing and neurodegenerative diseases.

6/ Role of Axonal Transport and Pathology in Neurodegeneration:

• Investigating how axonal transport impacts neurodegenerative diseases and its role in disease pathology.

7/ Role of Cytoplasmic p21 Cip1/WAF1 in Human Diseases:

• Understanding the involvement and impact of the cytoplasmic p21 Cip1/WAF1 protein in human diseases.

8/ Smart Use of 2D and 3D Cell Cultures for Drug Candidate Identification:

• Utilizing both two-dimensional (2D) and three-dimensional (3D) cell culture models to screen and characterize potential drug candidates effectively.

9/ Developing Physiologically Relevant Cellular Models (e.g., 3D Cultures, Organotypic Slices, iPSCs):

• Creating advanced cellular models, such as 3D cell cultures, organotypic slice cultures (e.g., brain and lungs), and induced pluripotent stem cells (iPSCs), for more accurate and physiologically relevant disease modelling and drug testing.