Biomarkers
Our mission is to use biomarkers to understand neuromuscular conditions.
We use a multidisciplinary approach to identify and validate molecular biomarkers in patients’ samples and back up the obtained results with data obtained in animal models. We make us of genomics, transcriptomics, proteomics and metabolomic platforms to identify molecular signatures in body fluids to describe disease progression over longitudinal studies and predict clinically meaningful milestones. This work includes development of quantitative lab methods, statistical modeling and omics data integration.
Spatial Biology
As we identify signature in body fluids that relate to how patients live and perform, we investigate how those omic signatures relate to the tissue alterations present in the affected skeletal muscle tissue.
For this purpose we use spatial technologies on histological sections such as spatial transcriptomics. With the use of this techniques we can then link the biomarkers signatures to changes in tissue morphology (e.g. fibrosis) and understand which cell types are involved.
We focus on several neuromuscular conditions such as Duchenne and Becker Muscular Dystrophies, Limb Girdle Muscular Dystrophies, Facioscapulohumeral Muscular Dystrophy and Inclusion Body Myositis where the cause of the disease is different, but pathophysiological changes are somewhat similar.
This work is typically done in muscle tissue, however given that dystrophin is also expressed in brain we are studying those changes in brain as well by single cell and spatial transcriptomics techniques.
RNA Biology
RNA targeting therapies such as exon skipping and read-through stop codons have shown promise in DMD patients. We have shown that dystrophin levels are however reduced compared to healthy counterparts downstream of the mutation site. We further showed that the dystrophin transcript is primarily located in the nucleus by Fluorescent In-Situ Hybridization (FISH). Quantification of nascent transcript has shown that the presence of premature termination codons leads to reduced pre-mRNA synthesis.
To further study the regulation of the synthesized mRNAs, we investigate the RNA binding proteome (interactome) of poly-A transcripts in muscle. We have described the poly-A interactome for proliferating and differentiated muscle cells and we are actively following on this for specific transcripts.