Dr. Sabina Tahirovic

Group Leader
The Ex vivo models group is associated to Prof. Dr. Herms chair

German Center for Neurodegenerative Diseases (DZNE)
Feodor-Lynen-Str. 17
81377 Munich

sabina.tahirovic@dzne.de
+49 (0) 89 / 4400-46438 (Office)
+49 (0) 89 / 4400-46508

Group members

Name Phone Fax
Dr. Alessio-Vittorio Colombo, Research Associate +49 (0)89/4400-46444 +49 (0)89/4400-46508
Robin Konhäuser, Studentische Hilfskraft +49 (0)89/4400-46468 +49 (0)89/4400-46508
Laura Sebastián Monasor, PhD Student +49 (0)89/4400-46444 +49 (0)89/4400-46508
Further group members (LMU/third party funding)
Anna Daria, PhD Student +49 (0)89/4400-46446 +49 (0)89/4400-46508
Former Group members
Stephanie Kunath,
Victoria Milde,
Andrea Wenninger-Weinzierl,
Nagore Astola,
Daniel Walz

Publications

Young microglia restore amyloid plaque clearance of aged microglia.

Daria A, Colombo A, Llovera G, Hampel H, Willem M, Liesz A, Haass C, Tahirovic S.EMBO J. 2017 Mar 1;36(5):583-603. doi: 10.15252/embj.201694591.
Comment: Reestablishing microglia function: good news for Alzheimer's therapy? By Knut Biber (EMBO J, 2017). Featured: EMBO cover (01 March 2017, Volume 36, Issue 5).

TDP-43 loss of function inhibits endosomal trafficking and alters trophic signaling in neurons.

Schwenk BM, Hartmann H, Serdaroglu A, Schludi MH, Hornburg D, Meissner F, Orozco D, Colombo A, Tahirovic S, Michaelsen M, Schreiber F, Haupt S, Peitz M, Brüstle O, Küpper C, Klopstock T, Otto M, Ludolph AC, Arzberger T, Kuhn PH, Edbauer D. EMBO J. 2016 Nov 2;35(21):2350-2370.

η-Secretase processing of APP inhibits neuronal activity in the hippocampus.

Willem M, Tahirovic S, Busche MA, Ovsepian SV, Chafai M, Kootar S, Hornburg D, Evans LD, Moore S, Daria A, Hampel H, Müller V, Giudici C, Nuscher B, Wenninger-Weinzierl A, Kremmer E, Heneka MT, Thal DR, Giedraitis V, Lannfelt L, Müller U, Livesey FJ, Meissner F, Herms J, Konnerth A, Marie H, Haass C. Nature. 2015 Oct 15;526(7573):443-7. doi: 10.1038/nature14864. Epub 2015 Aug 31.

Inhibition of amyloid-β plaque formation by α-synuclein.

Bachhuber T, Katzmarski N, McCarter JF, Loreth D, Tahirovic S, Kamp F, Abou-Ajram C, Nuscher B, Serrano-Pozo A, Müller A, Prinz M, Steiner H, Hyman BT, Haass C, Meyer-Luehmann M. Nat Med. 2015 Jul;21(7):802-7. doi: 10.1038/nm.3885. Epub 2015 Jun 22.

MicroRNA-125b induces tau hyperphosphorylation and cognitive deficits in Alzheimer's disease.

Banzhaf-Strathmann J, Benito E, May S, Arzberger T, Tahirovic S, Kretzschmar H, Fischer A, Edbauer D. EMBO J. 2014 Jul 7. pii: e201387576. 

TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis.

Kleinberger G, Yamanishi Y, Suárez-Calvet M, Czirr E, Lohmann E, Cuyvers E, Struyfs H, Pettkus N, Wenninger-Weinzierl A, Mazaheri F, Tahirovic S, Lleó A, Alcolea D, Fortea J, Willem M, Lammich S, Molinuevo JL, Sánchez-Valle R, Antonell A, Ramirez A, Heneka MT, Sleegers K, van der Zee J, Martin JJ, Engelborghs S, Demirtas-Tatlidede A, Zetterberg H, Van Broeckhoven C, Gurvit H, Wyss-Coray T, Hardy J, Colonna M, Haass C. Sci Transl Med. 2014 Jul 2;6(243):243ra86. doi: 10.1126/scitranslmed.3009093.

Common pathobiochemical hallmarks of progranulin-associated frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis.

Götzl JK, Mori K, Damme M, Fellerer K, Tahirovic S, Kleinberger G, Janssens J, van der Zee J, Lang CM, Kremmer E, Martin JJ, Engelborghs S, Kretzschmar HA, Arzberger T, Van Broeckhoven C, Haass C, Capell A. Acta Neuropathol. 2014 Jun;127(6):845-60. doi: 10.1007/s00401-014-1262-6. Epub 2014 Mar 12.

The FTLD risk factor TMEM106B and MAP6 control dendritic trafficking of lysosomes.

Schwenk BM, Lang CM, Hogl S, Tahirovic S, Orozco D, Rentzsch K, Lichtenthaler SF, Hoogenraad CC, Capell A, Haass C, Edbauer D. EMBO J. 2014 Mar 3;33(5):450-67. doi: 10.1002/embj.201385857. Epub 2013 Dec 19.

Bace1 and Neuregulin-1 cooperate to control formation and maintenance of muscle spindles.

Cheret C, Willem M, Fricker FR, Wende H, Wulf-Goldenberg A, Tahirovic S, Nave KA, Saftig P, Haass C, Garratt AN, Bennett DL, Birchmeier C.  EMBO J. 2013 Jul 17;32(14):2015-28. doi: 10.1038/emboj.2013.146. Epub 2013 Jun 21.

Dual cleavage of neuregulin 1 type III by BACE1 and ADAM17 liberates its EGF-like domain and allows paracrine signaling.

Fleck D, van Bebber F, Colombo A, Galante C, Schwenk BM, Rabe L, Hampel H, Novak B, Kremmer E, Tahirovic S, Edbauer D, Lichtenthaler SF, Schmid B, Willem M, Haass C.  J Neurosci. 2013 May 1;33(18):7856-69. doi: 10.1523/JNEUROSCI.3372-12.2013.

ADF/cofilin-mediated actin retrograde flow directs neurite formation in the developing brain.

Flynn KC, Hellal F, Neukirchen D, Jacob S, Tahirovic S, Dupraz S, Stern S, Garvalov BK, Gurniak C, Shaw AE, Meyn L, Wedlich-Söldner R, Bamburg JR, Small JV, Witke W, Bradke F.  Neuron. 2012 Dec 20;76(6):1091-107. doi: 10.1016/j.neuron.2012.09.038.

Arginine methylation next to the PY-NLS modulates Transportin binding and nuclear import of FUS.

Dormann D, Madl T, Valori CF, Bentmann E, Tahirovic S, Abou-Ajram C, Kremmer E, Ansorge O, Mackenzie IR, Neumann M, Haass C. EMBO J. 2012 Sep 11. doi: 10.1038/emboj.2012.261. [Epub ahead of print]

Requirements for stress granule recruitment of fused in Sarcoma (FUS) and TAR DNA binding protein of 43 kDa (TDP-43).

Bentmann E, Neumann M, Tahirovic S, Rodde R, Dormann D, Haass C. J Biol Chem. 2012 Jun 29;287(27):23079-94. Epub 2012 May 4.

Loss of fused in sarcoma (FUS) promotes pathological Tau splicing.

Orozco D, Tahirovic S, Rentzsch K, Schwenk BM, Haass C, Edbauer D. EMBO Rep. 2012 Aug 1;13(8):759-64. doi: 10.1038/embor.2012.90. Epub 2012 Jun 19.

Cholesterol-depletion corrects APP and BACE1 misstrafficking in NPC1-deficient cells.

Malnar M, Kosicek M, Lisica A, Posavec M, Krolo A, Njavro J, Omerbasic D, Tahirovic S, Hecimovic S. Biochim Biophys Acta. 2012 Apr 19;1822(8):1270-1283. [Epub ahead of print]

Electrical activity suppresses axon growth through Ca(v)1.2 channels in adult primary sensory neurons.

Enes J, Langwieser N, Ruschel J, Carballosa-Gonzalez MM, Klug A, Traut MH, Ylera B, Tahirovic S, Hofmann F, Stein V, Moosmang S, Hentall ID, Bradke F, 2010, Curr Biol. 20 (13), 1154-64

Rac1 regulates neuronal polarization through the WAVE complex.

Tahirovic S, Hellal F, Neukirchen D, Hindges R, Garvalov BK, Flynn KC, Stradal TE, Chrostek-Grashoff A, Brakebusch C, Bradke F, 2010, J Neurosci. 30 (20), 6930-43

Chronically CNS-Injured Adult Sensory Neurons Gain Regenerative Competence upon a Lesion of their Peripheral Axon.

Ylera B, Ertürk A, Hellal F, Nadrigny F, Hurtado A, Tahirovic S, Oudega M, Kirchhoff F, Bradke F, 2009, Curr. Biol. 19 (11), 930-6

Neuronal polarity.

Tahirovic, S and Bradke F, 2009, Cold Spring Harb Perspect Biol. 1(3), Review.

Inactivation of the phosphoinositide phosphatases Sac1 and Inp54 leads to accumulation of phosphatidylinositol 4,5-bisphosphate on vacuole membranes and vacuolar fusion defects.

Wiradjaja F, Ooms LM, Tahirovic S, Kuhne E, Devenish RJ, Munn AL, Piper RC, Mayinger P, Mitchell CA. 2007, JBC, 282 (22), 16295-307

Phosphoinositide synthesis and degradation in isolated rat liver peroxisomes.

Jeynov B, Lay D, Schmidt F, Tahirovic S, Just WW, 2006, FEBS Lett. 580 (25), 5917-5924

Cell growth-dependent coordination of lipid signaling and glycosylation is mediated by interactions between Sac1p and Dpm1p.

Faulhammer, F., Konrad G., Brankatschk B., Tahirovic S., Knödler A and Mayinger P, 2005, JCB. 168, 185-191

Regulation of intracellular phosphatidylinositol-4-phosphate by the Sac1 lipid phosphatase.

Tahirovic, S., Schorr M. and Mayinger, P, 2005, Traffic 6, 116-130

Role for lipid signaling and the cell integrity MAP kinase cascade in yeast septum biogenesis.

Tahirovic, S., Schorr M., Then A., Berger J., Schwarz H. and Mayinger, P, 2003, Curr. Genet. 43, 71-78

The phosphoinositide phosphatase Sac1 regulates secretion at the Golgi.

Schorr, M., Then, A. R., Tahirovic, S., Hug, N. and Mayinger, P, 2001, Curr. Biol. 11, 1421-1426

Curriculum Vitae

Dr. Tahirovic studied molecular biology at the University of Zagreb, Croatia (1994-1999) and was honored for her scientific achievements with the University of Zagreb Rector´s award (1998). For her graduate studies (2000-2004), she joined the laboratory of Prof. Dr. B. Dobberstein at the Center for Molecular Biology, University of Heidelberg (ZMBH). During that time, supervised by Prof. Dr. P. Mayinger, she studied the role of the yeast phosphoinositide phosphatase Sac1p in intracellular trafficking.

As postdoctoral fellow in Dr. F. Bradke´s group at the Max Planck Institute of Neurobiology in Munich (2005-2010), Dr. Tahirovic got interested in developmental neurobiology and analyzed the role of actin cytoskeleton and Rho GTPase Rac1 during neuronal polarization. She identified a crucial positive role of Rac1-dependent signalling in axon formation.

Since June 2010, Dr. Tahirovic is a group leader of the Ex vivo models at the DZNE in Munich. Her current research focuses on understanding the cellular and molecular basis of neurodegenerative diseases, in particular Alzheimer´s disease (AD) and Frontotemporal lobar degeneration (FTLD). To this end, she combines functional studies in cultured primary neurons and organotypic slice cultures with the in vivo analysis of transgenic animal models of neurodegenerative diseases.


Areas of investigation/research focus

Immunofluorescent image of cultured cerebellar granule neurons co-stained with rhodamine-phalloidin (magenta) to visualize actin cytoskeleton and an antibody against actin regulatory protein WAVE (green).
Immunofluorescent image of cultured cerebellar granule neurons co-stained with rhodamine-phalloidin (magenta) to visualize actin cytoskeleton and an antibody against actin regulatory protein WAVE (green).Click on the magnifying glass for a large image.

The aim of the "Ex vivo models" group is to provide state-of-the-art techniques in culturing cells from nervous tissues. Functional analysis of the cultured primary neurons has become a crucial research tool in understanding physiological and pathological changes in the central nervous system (CNS).
Our priority is to facilitate research projects aimed at understanding cellular and molecular mechanisms of neurodegenerative diseases, in particular focusing on Alzheimer, Parkinson and Frontotemporal lobar degeneration (FTLD). We offer assistance in culturing various nervous cells such as dissociated hippocampal, cortical, cerebellar or motor neurons as well as primary astrocytes or microglia. The advantage of these primary cellular systems is that particular nerve cells are isolated and cultured under defined conditions.

Immunofluorescent image of a cultured cerebellar explant immunostained with an antibody against Tuj1 to visualize migrating neurons.
Immunofluorescent image of a cultured cerebellar explant immunostained with an antibody against Tuj1 to visualize migrating neurons.Click on the magnifying glass for a large image.

The "Ex vivo models" group also provides training and assistance in real-time video microscopy of cultured neurons. This technique is beneficial in analyzing neuronal dynamics and axonal transport which, when perturbed, may contribute to neurodegeneration. Additionally, we provide expertise in explant and organotypic slice cultures in which nervous cells stay interconnected and where parts of their physiological neuronal networks remain intact.

Immunofluorescent image of cultured hippocampal neurons co-stained with rhodamine-phalloidin (red) to visualize actin cytoskeleton and an antibody against neuronal marker Tuj1 (green).
Immunofluorescent image of cultured hippocampal neurons co-stained with rhodamine-phalloidin (red) to visualize actin cytoskeleton and an antibody against neuronal marker Tuj1 (green).Click on the magnifying glass for a large image.

Furthermore, we aim at improving available tools and techniques to efficiently transfect primary neurons. Currently, this is a limiting step in manipulating gene expression. In our studies, we would like to combine the functional analysis of the cultured neurons with the phenotypic analysis of the loss- or gain-of-function transgenic animal models. Both systems are valuable for understanding the physiological function of genes involved in neurodegenerative diseases. This basic understanding will help in revealing new targets and developing disease modifying drugs.

The cooperation partner's homepage can be found here.