Department of Cellular and
Molecular Medicine

Vilhardt Group

By in vitro studies the Vilhardt Group try to approach fundamental unit operations in neuroinflammation and neurodegenerative disease with the aim of obtaining mechanistic insight.

Research interests

The lab has a long-standing interest in NADPH oxidase (NOX2) trafficking and function in macrophages and microglia (glia and macrophage cell of the CNS), and we continue to pursue the intricacies of NOX2 trafficking in the cell.

We are also interested in autophagy and the workings of the endosomal pathway in neurons under conditions of neurodegenerative cell stress, and recently our focus is on the ESCRT complex in endosomal and nuclear phenotypes of disease.

Brain-associated macrophages, including microglia, are important immune cells in neuroinflammation and we have recently engaged in a long-term collaboration with the Neurosurgical Department at Rigshospitalet, Copenhagen to investigate tumor-associated macrophages and their role in meningioma progression and post-operative morbidity.

Current project areas

NADPH Oxidase trafficking and function in macrophages
The ESCRT complex in frontotemporal dementia and spastic paraplegia
Tumor-associated macrophages in meningioma

Recent publications

Blum N, Mirian C, Maier AD, Mathiesen TI, Vilhardt F, Haslund-Vinding JL. Translocator protein (TSPO) expression in neoplastic cells and tumor-associated macrophages in meningiomas. J Neuropathol Exp Neurol. 82, 1020-1032 (2023).
Zang J, Peters F, Cambet Y, Cifuentes-Pagano E, Hissabu MMS, Dustin CM, Svensson LH, Olesen MM, Poulsen MFL, Jacobsen S, Tuelung PS, Narayanan D, Langkilde AE, Gajhede M, Pagano PJ, Jaquet V, Vilhardt F, Bach A. Targeting NOX2 with Bivalent Small-Molecule p47phox-p22phox Inhibitors. Journal of Medicinal Chemistry 66, 14963 (2023).
Borland H, Rasmussen I, Bjerregaard-Andersen K, Rasmussen M, Olsen A, Vilhardt F. α-synuclein buildup is alleviated via ESCRT-dependent endosomal degradation brought about by p38MAPK inhibition in cells expressing p25α. Journal of Biological Chemistry 298, 102531 (2022).
Haslund-Vinding J, Møller JR, Ziebell M, Vilhardt F, Mathiesen T. The role of systemic inflammatory cells in meningiomas. Neurosurgical Reviews 45, 1205-1215 (2022).
Villegas L, Nørremølle A, Freude K, Vilhardt F. Nicotinamide Adenine Dinucleotide Phosphate Oxidases Are Everywhere in Brain Disease, but Not in Huntington's Disease? Frontiers in Aging Neuroscience 5, 736734 (2021).

Teaching

Cell Biology and Histology for students of Medicin and Molecular Biology, or Medicin and Technology and Quantitative Biology (different courses).

Supervision of ERASMUS and graduate students in the lab.

Selected publications

Haslund-Vinding J, McBean G, Jaquet V, and Vilhardt F. NADPH oxidases in Microglia oxidant production: Activating Receptors, Pharmacology, and Association with Disease. British Journal of Pharmacology 174, 1733-1749 (2017).
Ploug Christensen, D., Ejlerskov, P., Rasmussen, I., and Vilhardt F. Reciprocal signals between microglia and neurons regulate α-synuclein secretion by exophagy through a neuronal JNK signaling axis. Journal of Neuroinflammation 13, 59 (2016)
Ejlerskov P, Christensen DP, Beyaie D, Burritt JB, Paclet MH, Gorlach A, van Deurs B, and Vilhardt F. NADPH Oxidase is Internalized by Clathrin-Coated Pits and Localizes to a Rab27A/B-Regulated Secretory Compartment in Activated Macrophages. Journal of Biological Chemistry, 287, 4835-52 (2012).
Ejlerskov, P., Rasmussen, I., Nielsen, T. T., Bergstrom, A. L., Tohyama, Y., Jensen, P. H., Vilhardt, F. Tubulin Polymerization Promoting Protein (TPPP/p25alpha) promotes unconventional secretion of alpha-synuclein through exophagy by impairing autophagosome-lysosome fusion. Journal of Biological Chemistry, 288, 17313 (2013).