Dr. Sabina Tahirovic

Keywords:
Alzheimer´s disease, Niemann Pick type C, Endo-lysosomal trafficking, Microglial repair, Neuroinflammation, Neurodegeneration, Biomarkers

Research methods:
We integrate ex vivo, primary and iPSC-derived cell culture models with in vivo, omics and translational approaches to identify pathomolecular mechanisms of neurodegeneration and reveal novel cellular targets to target and monitor neuroinflammation.

Brief research description:
We study the contribution of microglial cells and underlying mechanisms of neuroimmune dyshomeostasis in Alzheimer´s disease (AD) and the childhood dementia Niemann-Pick type C (NPC). In the focus of our research are endo-lysosomal and lipid trafficking defects that are early pathological hallmarks associated with microglial functional decline and neurodegeneration. Our translational efforts are dedicated to the identification of new therapeutic targets and blood- and imaging-based biomarkers to facilitate early disease diagnosis and therapeutic monitoring. Our interest in deciphering the role of microglial cells in disease pathology also integrates mechanisms of adaptive immunity and the contribution of T cells to neuroinflammation and neurodegeneration.

Selected publications:

1. Dinkel L, Hummel S, Zenatti V, Malara M, Tillmann Y, Colombo A, Monasor LS, Suh JH, Logan T, Roth S, Paeger L, Hoffelner P, Bludau O, Schmidt A, Müller SA, Schifferer M, Nuscher B, Njavro JR, Prestel M, Bartos LM, Wind-Mark K, Slemann L, Hoermann L, Kunte ST, Gnörich J, Lindner S, Simons M, Herms J, Paquet D, Lichtenthaler SF, Bartenstein P, Franzmeier N, Liesz A, Grosche A, Bremova-Ertl T, Catarino C, Beblo S, Bergner C, Schneider SA, Strupp M, Di Paolo G, Brendel M, Tahirovic S (2024) Myeloid cell-specific loss of NPC1 in mice recapitulates microgliosis and neurodegeneration in patients with Niemann-Pick type C disease. Sci Transl Med Dec 4;16(776):eadl4616. DOI:10.1126/scitranslmed.adl4616 

2. Colombo A, Dinkel L, Müller SA, Sebastian Monasor L, Schifferer M, Cantuti-Castelvetri L, König J, Vidatic L, Bremova-Ertl T, Lieberman AP, Hecimovic S, Simons M, Lichtenthaler SF, Strupp M, Schneider SA, Tahirovic S (2021) Loss of NPC1 enhances phagocytic uptake and impairs lipid trafficking in microglia. Nat Commun 12: 1158. DOI:10.1038/s41467-021-21428-5 

3. Colombo AV, Sadler RK, Llovera G, Singh V, Roth S, Heindl S, Sebastian Monasor L, Verhoeven A, Peters F, Parhizkar S, Kamp F, Gomez de Aguero M, MacPherson AJ, Winkler E, Herms J, Benakis C, Dichgans M, Steiner H, Giera M, Haass C, Tahirovic S*, Liesz A* (2021) Microbiota-derived short chain fatty acids modulate microglia and promote Abeta plaque deposition. Elife 10. DOI: 10.7554/eLife.59826 *contributed equally

4. Sebastian Monasor L, Müller SA, Colombo AV, Tanrioever G, König J, Roth S, Liesz A, Berghofer A, Piechotta A, Prestel M, Saito T, Saido TC, Herms J, Willem M, Haass C, Lichtenthaler SF, Tahirovic S (2020) Fibrillar Abeta triggers microglial proteome alterations and dysfunction in Alzheimer mouse models. Elife 9. DOI: 10.7554/eLife.54083

5. Daria A, Colombo A, Llovera G, Hampel H, Willem M, Liesz A, Haass C, Tahirovic S (2017) Young microglia restore amyloid plaque clearance of aged microglia. EMBO J 36: 583-603. DOI:10.15252/embj.201694591