Our research within DecOmPress has been focusing on two research tracks aiming at (1) decoding molecular signatures underlying chronic human neuroinflammatory diseases such as multiple sclerosis (MS) and (2) modeling and understanding dynamic trajectories underlying cell type-specific patterns of vulnerability and reactivity using in vivo models.
We have been working on data integration methods to decode molecular signatures related to gene regulation and expression in individual cell types across different regions of the central nervous system. For example, we found a strong level of regional diversity among glial subtypes in control tissue, whereas regional signatures across cell types were more obscure in MS. These findings suggest that molecular patterns in MS converge on specific pathways, especially those regulating cellular stress and immune activation across different anatomical regions. Furthermore, we observed that a disease subtype of oligodendrocytes adopts gene signatures related to repair and remyelination.
Another focus of DecOmPress has been on decoding cell type-specific pathologies underlying pathology along the visual pathway. Here, we have been focusing on dissecting transcriptomic signatures related to neuronal, glial and immune cell signatures in the retina and along the optic nerve in MS relative to control tissue. Preliminary data analysis suggests selective patterns of cell type vulnerability and reactivity that can be mapped back to specific anatomical areas such as the inflamed lesion rim in the MS optic nerve. Also, we have been investigating other brain border areas that are characterized by a close relationship between infiltrating immune cells and neuroglial cell types in MS and related diseases such as COVID-19. Using complex single-cell and spatially resolved transcriptomic tools, we have been studying mechanisms underlying sustained inflammation and tissue in the proximity of those brain-immune interfaces.
Additional work is focusing on the inflamed lesion rim, which is often observed in MS and corresponds to a high level of iron uptake as seen by magnetic resonance imaging. We have been dissecting this vulnerable area by applying multiplex imaging tools to human tissue specimens and found that haptoglobin-bound hemoglobin might be a critical source for iron uptake by myeloid cells at inflamed lesion rims. Further work is focusing on modeling these mechanisms using complex in vivo model systems. In addition, we have been developing focal lesion model systems to decode cell type-specific signatures related to neuronal and glial cell reactivity across time and space.
