Professor Gonçalo Castelo-Branco; Karolinska Institutet
Gonçalo Castelo-Branco is a Professor of Glial Cell Biology, Deputy Head of Department and Chair of Senate at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet, Stockholm, Sweden. Prof. Castelo-Branco received his B.Sc. in Biochemistry in 1999 at the University of Coimbra, Portugal and his PhD in Medical Biochemistry in 2005, at Karolinska Institutet in Sweden, working on the development of dopaminergic neurons, Parkinson’s disease and Wnt signalling. He completed post-doctoral fellowships first at the Karolinska Institutet and then at the University of Cambridge, United Kingdom, working in neural and pluripotentstem cells and chromatin. Prof. Castelo-Branco started his research group in 2012 at Karolinska Institutet, focusing on the molecular mechanisms regulating the epigenomic states of oligodendrocyte lineage cells in neuroinflammatory and demyelinating diseases such as multiple sclerosis (MS), using technologies such as single cell and spatial transcriptomics and epigenomics, among others. His research group has identified novel distinct oligodendroglia cell states in development and multiple sclerosis, including distinct disease-associated states, found that oligodendroglia is already primed at an epigenomic level at immune genes, to allow their transcription in neuroinflammatory environments. He has also developed in recent years novel single-cell and spatial epigenomics technologies. Prof.Castelo- Branco has received many prestigious honors/awards, including being elected member of the Nobel Assembly at Karolinska Institutet from 2023, Distinguished Professor within Medicine and Health of the Swedish Research Council (from 2024), Wallenberg Scholar (from 2024), the Hans Wigzell prize 2022, the Royal Swedish Academy of Sciences Göran Gustafsson Prize 2021 in Medicine, the Eric K. Fernström Prize 2021, the Swedish Society for Medical Research (SSMF) 100 years Jubileum Prize 2019 and European Research Council Consolidator (2015), Advanced (2023) and Proof of Concept (2025) Grants.
Oligodendroglia (OLG) mediate myelination of neurons, a process that allows efficient electrical impulse transmission in the central nervous system. An autoimmune response in multiple sclerosis (MS) leads to OLG cell death, loss of myelin and neuropathology. Using single cell transcriptomics, we have previously identified disease-specific OLG populations in the EAE mouse model of MS and in human MS brain archival tissue, characterized by the expression of immune genes. By assessing chromatin accessibility and the transcriptome simultaneously at the single cell level at different stages of the disease course, we found that immune genes exhibit a primed chromatin state in mouse and human OLG in a non-disease context, compatible with rapid transitions to immune-competent states in MS. Moreover, we found dynamic and distinct transcriptomic and epigenomic responses of OLG subpopulations to the evolving environment in EAE mouse model of MS, which might modulate their response to regenerative therapeutic interventions in MS. While single-cell genomics are powerful for investigating disease-specific cellular states, these methods involve isolating the tissue under study from its niche, leading to a loss of spatial information. Such information is essential for determining cell-to-cell communication in disease niches. We have applied in situ sequencing to investigate disease evolution in MS at a spatial level, both in the EAE mouse model of MS and inhuman post-mortem MS samples. We annotated disease neighborhoods during lesion evolution and found centrifugal propagation of active lesions. We demonstrated that disease-associated (DA)-glia arise independently of lesions and are dynamically induced and resolved over the disease course. We have also applied dBIT-Seq, a ligation-based method for deterministic barcoding in tissue, to probe different histone modifications and chromatin accessibility in the mouse brain tissue sections, either in an unimodal or simultaneously with transcriptomics. This spatial epigenome–transcriptome co-profiling has allowed us to identify cellular lineage progression and epigenomic priming events that precede transcription during development with spatial resolution. We are currently applying these methods to disease paradigms in MS, to uncover how transitions to pathological cellular states occur at epigenomic and transcriptomic levels.
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