Immunostroke – FROM IMMUNE CELLS TO STROKE RECOVERY

Dirk Hermann studied medicine at Justus Liebig University Gießen from 1987-1994. Following his MD thesis at the same University in 1995 and a residency (Arzt im Praktikum) at the Max Planck Institute of Psychiatry Munich in 1994-1995, he performed a postdoc at the Max Planck Institute for Neurological Research Cologne in 1995-1998, followed by his residency at the Department of Neurology of Eberhard Karls University Tübingen in 1998-2001. Following his neurological board examination in 2001 and his state doctorate (habilitation) in 2002, Dirk Hermann was associate professor and consultant neurologist at the University Hospital Zurich (Switzerland) in 2002-2008. Since 2008, Dirk Hermann holds the Chair of Vascular Neurology, Dementia and Ageing Research at the University of Duisburg-Essen.  

Dirk Hermann’s research focusses on post-ischemic brain remodeling and plasticity, evaluating pathomechanisms contributing to secondary brain injury and searching strategies that promote neurological recovery in the post-acute stroke phase. Research activities include studies on post-ischemic axonal, dendritic and synaptic plasticity, angiogenesis, extracellular matrix remodeling, immune responses and vascular risk factors. Dirk Hermann’s group has long-lasting experience and skills in the evaluation of post-ischemic blood-brain barrier integrity. The group bridges in vitro and in vivo studies in animals and humans, combining structural and functional readouts with a broad set of research tools. 

Bacigaluppi M, Pluchino S, Peruzzotti-Jametti L, Kilic E, Kilic U, Salani G, Brambilla E, West MJ, Comi G, Martino G, Hermann DM. Delayed post-ischaemic neuroprotection following systemic neural stem cell transplantation involves multiple mechanisms. Brain. 2009; 132:2239-51.

ElAli A, Hermann DM. Apolipoprotein E controls ATP-binding cassette transporters in the ischemic brain. Sci Signal. 2010; 3:ra72. 

Hermann DM, Bassetti CL. Implications of ATP-binding cassette transporters for brain pharmacotherapies. Trends Pharmacol Sci. 2007; 28:128-34.

Hermann DM, Chopp M. Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation. Lancet Neurol. 2012; 11:369-80.

Hermann DM, ElAli A. The abluminal endothelial membrane in neurovascular remodeling in health and disease. Sci Signal. 2012; 5:re4.

Kilic E, Spudich A, Kilic U, Rentsch KM, Vig R, Matter CM, Wunderli-Allenspach H, Fritschy JM, Bassetti CL, Hermann DM. ABCC1: a gateway for pharmacological compounds to the ischaemic brain. Brain. 2008; 131:2679-89.

Reitmeir R, Kilic E, Kilic U, Bacigaluppi M, ElAli A, Salani G, Pluchino S, Gassmann M, Hermann DM. Post-acute delivery of erythropoietin induces stroke recovery by promoting perilesional tissue remodelling and contralesional pyramidal tract plasticity. Brain. 2011; 134:84-99.

Reitmeir R, Kilic E, Reinboth BS, Guo Z, ElAli A, Zechariah A, Kilic U, Hermann DM. Vascular endothelial growth factor induces contralesional corticobulbar plasticity and functional neurological recovery in the ischemic brain. Acta Neuropathol. 2012; 123:273-84.

Spudich A, Kilic E, Xing H, Kilic U, Rentsch KM, Wunderli-Allenspach H, Bassetti CL, Hermann DM. Inhibition of multidrug resistance transporter-1 facilitates neuroprotective therapies after focal cerebral ischemia. Nat Neurosci. 2006; 9:487-8. 

Nina Hagemann (born Stenzel) studied biology at the Ruhr University Bochum and received her diploma in 2007. Her diploma thesis focussed on the hitherto unknown FERM and PDZ domain containing protein 2 and its expression in epithelial cells. Nina Hagemann performed her dissertation in the research group “Biochemistry of polarized cells” at the Department of Molecular Neurobiochemistry of the Faculty of Chemistry and Biochemistry at the Ruhr University Bochum under the supervision of PD Dr. Kai S. Erdmann from 2007 until 2011. Her thesis entitled “Functional characterisation of the PDZ domain proteins FRMPD2 and PTP-BL in polarized cells” was awarded with the grade “with distinction”. After a subsequent post-doc time she moved to the University Hospital Essen and joined the NeuroScienceLab within the Chair of Vascular Neurology, Dementia and Ageing Research in 2012.

Nina Hagemann is interested in the role of transporters, receptors and sphingolipids in the ischemic brain with special emphasis on blood-brain barrier integrity and angiogenesis. Her group utilizes a wide range of in vitro and in vivo methods, evaluating restorative processes also in the context of vascular risk factors and comorbidities.

Lugo-Hernandez E, Squire A, Hagemann N, Brenzel A, Sardari M, Schlechter J, et al. 3D visualization and quantification of microvessels in the whole ischemic mouse brain using solvent-based clearing and light sheet microscopy. J Cereb Blood Flow Metab. 2017: 271678X17698970.

Zechariah A, ElAli A, Hagemann N, Jin F, Doeppner TR, Helfrich I, et al. Hyperlipidemia attenuates vascular endothelial growth factor-induced angiogenesis, impairs cerebral blood flow, and disturbs stroke recovery via decreased pericyte coverage of brain endothelial cells. Arterioscler Thromb Vasc Biol. 2013; 33(7):1561-7.

Jin F, Hagemann N, Schafer ST, Brockmeier U, Zechariah A, Hermann DM. SDF-1 restores angiogenesis synergistically with VEGF upon LDL exposure despite CXCR4 internalization and degradation. Cardiovasc Res. 2013; 100(3):481-91.

Jin F, Hagemann N, Brockmeier U, Schafer ST, Zechariah A, Hermann DM. LDL attenuates VEGF-induced angiogenesis via mechanisms involving VEGFR2 internalization and degradation following endosome-trans-Golgi network trafficking. Angiogenesis. 2013; 16(3):625-37.

Hagemann N, Ackermann N, Christmann J, Brier S, Yu F, Erdmann KS. The serologically defined colon cancer antigen-3 interacts with the protein tyrosine phosphatase PTPN13 and is involved in the regulation of cytokinesis. Oncogene. 2013; 32(39):4602-13.

Lipinski S, Grabe N, Jacobs G, Billmann-Born S, Till A, Hasler R, et al., Hagemann N, et al. RNAi screening identifies mediators of NOD2 signaling: implications for spatial specificity of MDP recognition. Proc Natl Acad Sci U S A. 2012; 109(52):21426-31.

Hagemann N, Hou X, Goody RS, Itzen A, Erdmann KS. Crystal structure of the Rab binding domain of OCRL1 in complex with Rab8 and functional implications of the OCRL1/Rab8 module for Lowe syndrome. Small GTPases. 2012; 3(2):107-10.

Hou X, Hagemann N, Schoebel S, Blankenfeldt W, Goody RS, Erdmann KS, et al. A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1. EMBO J. 2011; 30(8):1659-70.

Stenzel N, Fetzer CP, Heumann R, Erdmann KS. PDZ-domain-directed basolateral targeting of the peripheral membrane protein FRMPD2 in epithelial cells. J Cell Sci. 2009; 122(Pt 18):3374-84.

 Ayan Mohamud Yusuf received her Master of Science degree in Medical Biology in 2015 from the University Duisburg-Essen for a thesis, in which she examined ceramide changes in neuroblastoma cells exposed to ischemia-reperfusion injury. She subsequently performed her PhD studies in the DFG-funded Research Training Group 2098 (“Biomedicine of sphingolipids”) under the supervision of Prof. Dirk M. Hermann, evaluating consequences of the acid sphingomyelinase / ceramide system for ischemic stroke development and recovery. As a post-doctoral fellow within the research consortium FOR 279, Ayan Mohamud Yusuf studies the role of inflammatory processes in repair mechanisms and long-term recovery following stroke.

Ayan Mohamud Yusuf is interested in the role of microglia and T cells in controlling microvascular integrity and the contribution of angiogenesis for post-stroke recovery. Furthermore, she analyzes how bioactive sphingolipids such as ceramide control brain injury and remodeling after ischemic stroke