Dr. Sarah Jaekel (née Schneider)

Thesis Title: Proliferating NG2-glia and their functional importance in the healthy and injured brain

Supervisor: Dr. Leda Dimou

Current GSN Student: Courtney McQuade

Keywords: oligodendrocytes, neurodegeneration, human pathology, iPSC

Research description: We are interested in the role of oligodendrocytes – the myelin forming cells in the central nervous system – in Alzheimer’s disease. For decades, the pathology in Alzheimer’s has been considered purely neuronal, however, recent advances have clearly demonstrated glial involvement, initiating a shift in scientific focus. Oligodendrocytes have been shown to be the first cell type to transcriptionally change in the earliest stages of the disease, while the functional importance of these changes still remains unknown. With an expertise in human oligodendrocyte biology, our lab aims to describe changes in the cellular distribution of oligodendrocytes in the human brain and to unravel how their functional changes contribute to the pathogenesis of Alzheimer’s disease.

Selected publications:

1. Jäkel S, Williams A. What Have Advances in Transcriptomic Technologies Taught us About Human White Matter Pathologies? Front Cell Neurosci. 2020 Aug 4;14:238. DOI: 10.3389/fncel.2017.00024

2. Jäkel S, Agirre E, Mendanha Falcão A, van Bruggen D, Lee KW, Knuesel I, Malhotra D, Ffrench-Constant C, Williams A, Castelo-Branco G. Altered human oligodendrocyte heterogeneity in multiple sclerosis. Nature. 2019 Feb;566(7745):543-547. doi: 10.1038/s41586-019-0903-2

3. Falcão AM, van Bruggen D, Marques S, Meijer M, Jäkel S, Agirre E, Samudyata, Floriddia EM, Vanichkina DP, Ffrench-Constant C, Williams A, Guerreiro-Cacais AO, Castelo-Branco G. Disease-specific oligodendrocyte lineage cells arise in multiple sclerosis. Nat Med. 2018 Dec;24(12):1837-1844. doi: 10.1038/s41591-018-0236-y

4. Fard MK, van der Meer F, Sánchez P, Cantuti-Castelvetri L, Mandad S, Jäkel S, Fornasiero EF, Schmitt S, Ehrlich M, Starost L, Kuhlmann T, Sergiou C, Schultz V, Wrzos C, Brück W, Urlaub H, Dimou L, Stadelmann C, Simons M. BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions. Sci Transl Med. 2017 Dec 6;9(419):eaam7816. doi: 10.1126/scitranslmed.aam7816

5. Schneider S, Gruart A, Grade S, Zhang Y, Kröger S, Kirchhoff F, Eichele G, Delgado García JM, Dimou L. Decrease in newly generated oligodendrocytes leads to motor dysfunctions and changed myelin structures that can be rescued by transplanted cells. Glia. 2016 Dec;64(12):2201-2218. doi: 10.1002/glia.23055