Vahsen Lab

Neuro-immune mechanisms of neurodegeneration

We investigate how neuro-immune interactions drive neurodegenerative diseases, with a particular focus on the role of microglia in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Using human iPSC models, our aim is to understand disease mechanisms and identify novel therapeutic targets.

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Our research

We study the cellular and molecular mechanisms of neurodegeneration. We are particularly interested in the role of microglia in major neurodegenerative diseases. Our main focus is on amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two closely related diseases with overlapping clinical phenotype, genetics, and pathology.

We combine human patient-derived iPSC models of increasing cellular complexity with ‘omics and high-throughput imaging approaches to:

1. Understand how genetic ALS/FTD variants impact on microglial biology,
2. Dissect the mechanisms by which microglia drive neurodegeneration in ALS/FTD,
3. Translate this fundamental mechanistic knowledge into novel therapies.

Current projects

Microglia in C9orf72-ALS/FTD

Hexanucleotide repeat expansions (HRE) in C9orf72 are the most common genetic cause of both ALS and FTD. Notably, C9orf72 expression is particularly high in microglia, suggesting a key role for C9orf72 in microglial function. We have previously demonstrated that human iPSC microglia carrying the C9orf72 HRE upregulate pro-inflammatory pathways and reduce the survival of motor neurons via dysregulated MMP-9 release (Vahsen et al., 2023). We are now investigating in greater detail how the C9orf72 HRE impacts microglial biology and the specific mechanisms underlying non-cell-autonomous neurotoxicity.

Microglia and TDP-43

Mislocalisation and aggregation of TDP-43 are defining features of ALS and many cases of FTD. Variants in TARDBP (which encodes TDP-43) are also a frequent cause of ALS/FTD. However, the impact of TDP-43 dysfunction on microglial biology remains poorly understood. Using complementary approaches, we investigate inflammatory changes in TARDBP mutant microglia and the interplay between neuronal TDP-43 proteinopathy and microglia.

Advanced neuro-immune models for ALS/FTD

Microglial function is strongly shaped by the cellular environment, including interactions with other neuronal and non-neuronal cell types. We have developed and characterised the first protocol for iPSC-derived motor neuron-microglia co-cultures (Vahsen et al., 2022). We are now developing increasingly complex iPSC-derived model systems to study how microglia interact with and influence other cell types, and how these interactions in turn shape microglial function. These models will provide us with a more refined understanding of neuro–immune interactions in health and disease.

News

May 2026

We are hiring! We are recruiting the first PhD student for our new lab at the University of Aberdeen! This fully funded project (Home/UK fees) will investigate how microglia, astrocytes, and motor neurons interact in amyotrophic lateral sclerosis (ALS), using advanced human stem cell models and ‘omics approaches.

The project is ideal for a motivated student interested in neurodegeneration, glial biology and stem cell models, and offers the opportunity to help shape a new and ambitious research programme focused on ALS/FTD mechanisms and therapeutics.

More details and application information: https://www.findaphd.com/phds/project/dissecting-microglia-astrocyte-crosstalk-in-amyotrophic-lateral-sclerosis-using-human-stem-cell-models/?p196722

April 2026

We are excited that the Vahsen Lab will be opening at the University of Aberdeen in July 2026. We will be advertising a funded PhD position and Postdoc position soon – join us!

Our team

Björn Vahsen, MD DPhil
SSIG Lecturer in Neuroimmunology &
MND Association Lady Edith Wolfson Fellow

Björn’s research focuses on the cellular and molecular mechanisms of neurodegenerative diseases, particularly ALS and FTD. His work has identified a key role for human microglia in ALS/FTD with C9orf72 hexanucleotide repeat expansions. His research has been recognised with multiple international awards, including the BNA Postgraduate Prize (2023), the Felgenhauer Research Award of the German Neurological Society (2023), the Junior Research Prize of the German Society for Muscular Diseases (2025), and the ENCALS Young Investigator Award Gold Medal (2025).

Björn studied Medicine and completed his medical doctorate at the University of Göttingen, before undertaking an MSc/DPhil in Clinical Neurosciences and postdoctoral work at the University of Oxford. In 2024, he was a Visiting Research Fellow at Memorial Sloan Kettering Cancer Center in New York. In 2026, he was awarded an independent fellowship from the MND Association and appointed SSIG Lecturer in Neuroimmunology at the University of Aberdeen to start his research group.

Lara Nikel, MSc
PhD Student

Lara is a third-year PhD student in Clinical Neurosciences at the University of Oxford, jointly supervised with Kevin Talbot. Her research uses human iPSC models to study the role of TDP-43 in microglia, with a focus on how mutations in TARDBP affect microglial biology and microglia–motor neuron interactions. She is funded by an MND Scotland PhD studentship and has secured additional funding from Alzheimer’s Research UK, the Rosetrees Trust and the Stoneygate Trust.

Lara studied Psychology at the University of York before completing an MSc in Neuroscience at the University of Oxford. Following a year as a research assistant with Matthew Wood, she began her PhD with us in October 2023.

You?

We are currently looking for a PhD student and Postdoc to help us answer exciting questions about microglia in ALS. Please reach out to Björn if you are interested.

Publications

2026

Vahsen BF^#, Pasterkamp RJ^#. Microglia in C9orf72–associated amyotrophic lateral sclerosis: More or less active? Neural Regen Res 21, tbc. PMID: 41495602. #shared corresponding authors

2025

Sonustun B, Vahsen BF, Ledesma-Terrón M, Li Z, Xu N, Calder EL, Jungverdorben J, Weber L, Zhong A, Gómez AM, Monetti M, Zhou T, Giacomelli E^#, Studer L^#. Telmisartan is neuroprotective in a hiPSC-derived spinal microtissue model for C9orf72-ALS via inhibition of neuroinflammation. Stem Cell Rep 20, 102535. PMID: 40541176. #shared corresponding authors

Dellar ER, Nikel L, Fowler S, Vahsen BF, Dafinca R, Feneberg E, Talbot K, Turrner MR, Thompson AG. Extracellular vesicles in TDP-43 proteinopathies: pathogenesis and biomarker potential. Mol Neurodegeneration 20, 68. PMID: 40495245

Luteijn MJ^#, Bhaskar V, Trojer D, Schürz M, Mahboubi H, Handl C, Pizzato N, Pfeifer M, Dafinca R, Voshol H, Giorgetti E, Manneville C, Garnier IPM, Müller M, Zeng F, Buntin K, Markwalder R, Schröder H, Weiler J, Khar D, Schuhmann T, Groot-Kormelink PJ, Keller CG, Farmer P, MacKay A, Beibel M, Roma G, D’Ario G, Merkl C, Schebesta M, Hild M, Elwood F, Vahsen BF, Ripin N, Clery A, Allain F, Labow M, Gabriel D, Chao JA, Talbot K, Nash M, Hunziker J^#, Meisner-Kober NC^#: High-throughput screen of 100 000 small molecules in C9ORF72 ALS neurons identifies spliceosome modulators that mobilize G4C2 repeat RNA into nuclear export and repeat associated non-canonical translation. Nucleic Acids Res 53, gkaf253. PMID: 40207633.

2024

Dafinca R, Tosat-Bitrian C, Carroll E, Vahsen BF, Gilbert-Jaramillo J, Scaber J, Feneberg E, Johnson E, Talbot K: Dynactin-1 mediates rescue of impaired axonal transport due to reduced mitochondrial bioenergetics in amyotrophic lateral sclerosis motor neurons. Brain Commun fcae350. PMID: 39440303.

Scaber J^#, Thomas-Wright I, Clark A, Xu Y, Vahsen BF, Carcolé M, Dafinca R, Farrimond L, Isaacs AM, Bennett DL, Talbot K^#: Cellular and axonal transport phenotypes due to the C9orf72 HRE in iPSC-motor and sensory neurons. Stem Cell Rep 19, 957-972. PMID: 38876108. #shared corresponding authors

Nikel LM, Talbot K^#, Vahsen BF^#: Recent insights from human induced pluripotent stem cell models into the role of microglia in amyotrophic lateral sclerosis. BioEssays, 46, e2400054. PMID: 38713169. #shared corresponding authors

2023

Vahsen BF, Nalluru S, Morgan GR, Farrimond L, Carroll E, Xu Y, Cramb KML, Amein B, Scaber J, Katsikoudi A, Candalija A, Carcolé M, Dafinca R, Isaacs AM, Wade-Martins R, Gray E, Turner MR, Cowley SA^#, Talbot K^#: C9orf72-ALS human iPSC microglia are pro-inflammatory and toxic to co-cultured motor neurons via MMP9. Nat Commun 14, 5898. PMID: 37736756. #shared corresponding authors

2022

Vahsen BF, Gray E, Candalija A, Cramb KLM, Scaber J, Dafinca R, Katsikoudi A, Xu Y, Farrimond L, Wade-Martins R, James WS, Turner MR, Cowley SA^#, Talbot K^#: Human iPSC co-culture model to investigate the interaction between microglia and motor neurons. Sci Rep 12, 12606. PMID: 35871163. #shared corresponding authors

GiacomelliE*, Vahsen BF*, Calder EL, Xu Y, ScaberJ, Gray E, Dafinca R, Talbot K^#, StuderL^#: Human stem cell models of neurodegeneration: From basic science of amyotrophic lateral sclerosis to clinical translation. Cell Stem Cell 29, 11-35. PMID: 34995492. *shared first authors #shared corresponding authors

2021

Ribas VT*, Vahsen BF*, Tatenhorst L, Estrada V, Dambeck V, de Almeida RA, Bähr M, Michel U, Koch JC, Müller HW, Lingor P: AAV-mediated inhibition of ULK1 promotes axon regeneration in the central nervous system in vitro and in vivo. Cell Death Dis 12, 213. PMID: 33637688. *shared first authors

Vahsen BF, Gray E, Thompson AG, Ansorge O, Anthony DC, Cowley SA, Talbot K^#, Turner MR^#: Non-neuronal cells in amyotrophic lateral sclerosis — from pathogenesis to biomarkers. Nat Rev Neurol 17, 333–348. PMID: 33927394. #shared corresponding authors

2020

Vahsen BF, Lingor P: ULK1 as a novel therapeutic target in neurodegeneration. Neural Regen Res 16, 1212-1213. PMID: 33269781.

Vahsen BF*, Ribas VT*, Sundermeyer J, Boecker A, Dambeck V, Lenz C, Shomroni O, Caldi Gomes L, Tatenhorst L, Barski E, Roser AE, Michel U, Urlaub H, Salinas G, Bähr M, Koch JC, Lingor P: Inhibition of the autophagic protein ULK1 attenuates axonal degeneration in vitro and in vivo, enhances translation, and modulates splicing. Cell Death Differ 27, 2810–2827. PMID: 32341448. *shared first authors

2019

Balke D*, Tatenhorst L*, Dambeck V, Ribas VT, Vahsen BF, Michel U, Bähr M, Lingor P: AAV-mediated expression of dominant-negative ULK1 increases neuronal survival and enhances motor performance in the MPTP mouse model of Parkinson’s disease. Mol Neurobiol 57, 685–697. PMID: 31446549. *shared first authors

Funding

Our work is made possible through competitive grants and philanthropic support. We are very grateful to the following organisations for funding our past and present work: