Jäkel Lab – Oligodendrocyte Pathology
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.
Our work is based on the observation that developmental cortical myelination does not happen all at once and late myelinated regions are affected earlier by Alzheimer’s disease than early myelinated ones. My previous work revealed oligodendrocytes in the human brain are heterogeneous, representing different states that might exhibit different functions. In the context of Alzheimer’s disease, this could in turn influence the vulnerability of neurons to degenerate within different brain areas. Hence, by understanding the distribution and the function of different oligodendrocyte states we aim to explain why some brain regions are more affected by Alzheimer’s than others.
Our research focuses on the human disease itself rather than mimicking it in animal models and is thus highly translational. We use a combination of cutting-edge transcriptomic approaches such as single-nuclei RNA-sequencing on post-mortem human brain tissue, as well as two and three-dimensional human stem cell-derived oligodendrocyte cultures as model systems in which we recreate and characterize the functional oligodendrocyte cell states.
Contact: Dr. Sarah Jäkel
Read more about the PI on the next tab.
I am originally from the United States, where I earned my BSc in Psychological Sciences and Neuroscience from the University of Connecticut. During my studies there, I worked as a research assistant in the Behavioural Neuroscience department studying the effects of nicotine addiction on conditioning and responsiveness to non-nicotine rewards in humans. In 2018, I moved to Munich to pursue an MSc degree with the Graduate School of Systemic Neurosciences (GSN) at LMU. I completed my Master thesis project at the LMU Munich Biomedical Center - Department of Neuroimmunology in Dr. Anneli Peters’ lab investigating pathogenic B cell properties in CNS autoimmunity using CRISPR/Cas9. I joined the ISD as a PhD candidate in the group of Dr. Sarah Jäkel in August 2021 to study oligodendrocyte involvement in the pathogenesis of Alzheimer’s disease using a model of myelinating human iPSC-derived brain organoids.
I’m originally from Nördlingen, a city “near” Augsburg (70 km away) on the border to Baden-Württemberg. Three years ago, I came to Munich to start my MTLA (medical-technical laboratory assistant) degree at the Max von Pettenkofer Institute.
In September 2021, immediately after my graduation, I joined the Jäkel Lab as a research assistant. I am involved in different projects and I am supporting the team in every way. This includes e.g. working with cell culture with human iPSCs, iPSC-derived oligodendrocytes and organoids, performing immunostainings, as well as taking care of organizational issues and maintaining the lab supplies and equipment.
Originally from Iran, I am currently a master’s student at LMU’s Graduate School for Systemic Neurosciences (GSN). Prior to moving to Munich, I completed my undergraduate studies at the University of California, San Diego (UCSD), where I obtained a B.Sc. in psychology with a specialization in clinical neuropsychology. My research interests include the molecular and cellular mechanisms underlying the pathogenesis of neurodegenerative diseases, specifically Alzheimer’s disease (AD). I joined Dr. Jäkel’s lab in July 2021 to learn more about oligodendrocyte involvement in AD pathology. For my master’s thesis project, I am investigating the vulnerability of iPSC-derived oligodendrocytes to AD-related stress, also taking into account genetic factors.
Dr. Sarah Jäkel
I am fascinated by the biology of oligodendrocytes: they are small cells producing large amounts of membrane, which can be >100 times the surface of their cell body and wrap it in a highly organized way around several axons. Most of this happens after birth, when the major parts of the brain, including neurons, are already fully developed. Oligodendrocytes and myelin are probably the most plastic parts in our brain and keep changing until the end of our lifetime. They are indispensable for a fast saltatory nerve conduction and thus making our body work as it should, but also for providing metabolic support to the otherwise insulated axons to keep them healthy.
It is not surprising that malfunctioning oligodendrocytes are involved in numerous neurological disorders including neurodegenerative diseases, in which oligodendrocytes have long been neglected. I studied oligodendrocytes in mouse models during my PhD at the department of Physiological Genomics at the LMU, but then I decided to move to translational neuroscience studying diseases directly on human tissue. Although disease models are of highest importance in science, the accompanying use of human tissue is essential and complementary to understanding human disease pathology. I then studied oligodendrocytes in Multiple Sclerosis in my postdoctoral time at the Centre for Regenerative Medicine at the University of Edinburgh. Studying oligodendrocytes in neurodegenerative diseases is exciting for me, because almost nothing is known about their involvement in the disease, leaving a lot to explore. Moreover, this research topic is of high importance from a clinical perspective. Due to their highly plastic nature, oligodendrocytes are more tractable to therapy than for examples neurons, thus opening completely new possibilities for drug development in Alzheimer’s disease and possibly other forms of dementia.
I also enjoy being engaged in science communication activities for the general public including children. In my eyes, it is important that non-scientists get a better and more realistic picture of our work and that all children have an equal chance to understand science.
2021 onwards: Emmy-Noether junior group leader, Institute for Stroke and Dementia Research, LMU Munich.
2016-2020: Marie-Sklodowska Curie Postdoctoral Research Fellow, Centre for Regenerative Medicine, University of Edinburgh
2012-2016: PhD, Graduate School of Systemic Neuroscience and Department of Physiological Genomics, LMU Munich
2009-2011: MSc, Molecular Biotechnology, TU Munich
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.