We use the cuprizone (CPZ) model of experimental de- and remyelination to examine (i) microRNA, (ii) transcriptome, (iii) and proteome/post-translational proteome of de- and remyelination in the brain. By using these databases, we found that absence of miR-146a protects against demyelination and increases microglia function. We identified homologous genes in multiple sclerosis (MS) lesions related to de- and remyelination by overlapping transcriptome of MS lesions with the CPZ transcriptomes. We quantified 130 peptides of these genes in the 97 CSF by targeted proteomics, and identified 4 proteins differentially regulated between progressive and relapsing MS: all expressed during acute remyelination and correlate negatively pro-inflammatory responses. (manuscripts in prep)
We performed next-generation RNA sequencing of 73 brain lesions of progressive MS that covers the different phases of lesion evolution, and 25 contols brain areas. We establish the transcriptome signature of MS lesion evolution, and look for endogeneous and exogeneous viral sequences. We link these data to genome-wide DNA methylation and proteome/metabolome of the same MS lesions in order to examine epigenetic effect of viral sequences and their association with lesion evolution. We also plan to examine if these transcriptome signatures are differentially regulated in the CSF proteome of relapsing versus progressive MS as potential composite biomarkers predicting disease progression.
In our prospective ProActive study, we examined social cognition and emotion recognition in 85 MS patients and correlate data with eye motion, cognition, optical coherence tomography (OCT) and clinical outcomes. We also examine biomarkers related to axonal damage and neuroinflammation in the CSF of MS patients after a novel oral treatment in our prospective , ongoing TREMEND trial. We also used frequent MRI combined with protein array, proteomics and endothelial-microvesicle array to examine pathogenesis and biomarkers related to inflammatory blood-brain barrier disruption (manuscripts partly in prep)