Group name: Lambertsen Lab
Group leader: Prof., PhD Kate Lykke Lambertsen
Group members: 1 Post doc, 3 PhD students, 3 Medical students, 6 Master students and 2 Technicians.
Department & University/Hospital/Other: Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark and Department of Neurology, Odense University Hospital
Funding sources: The Lundbeck Foundation, The Danish Council for Independent Research – Medical Research, The Danish Victims Found and several private foundations.
Description of research:
In our laboratory we are studying cerebrovascular diseases of and trauma to the central nervous system (CNS), such as stroke and spinal cord injury (SCI), to try to understand the cellular and molecular mechanisms that contribute to inflammation and secondary neuronal cell death. We have primarily one main research objective, which is to study the neuro-inflammatory response that occurs following stroke and SCI with the aim to contribute to the development of novel therapies for stroke and SCI patients.
To determine what role inflammation plays following CNS injury we use transgenic mouse models and other molecular approaches to study the central but complex role of the pleiotrophic cytokine tumor necrosis factor (TNF) for neuronal survival/death. We specifically use conventional and conditional knock out models in which TNF and/or its receptors can be manipulated in all cells or in tissue specific cells, including microglia, leukocytes, oligodendrocytes and neurons. We also use a variety of anti-TNF drugs targeting both the transmembrane and the soluble forms of TNF in order to elucidate the very complex role of this signaling molecule in modulating neuroinflammation following CNS injury.
We hope to be be able to contribute to identifying novel neuroprotective therapeutics for treatment in stroke and SCI.
Key publications (last 10 years):
1. Lambertsen KL, Clausen BH, Babcock AA, Gregersen R, Nielsen M, Wirenfeldt M, Haugaard LS, Færgemann NJ, Dagnaes-Hansen F, Bluethmann H, Meldgaard M, Deierborg T, Finsen B (2009) Microglia protect neurons against ischemia by synthesis of tumor necrosis factor. J Neurosci, 29:1319-1330.
2. Novrup HG, Bracchi-Ricard V, Ellman DG, Ricard J, Jain A, Runko E, Lyck L, Yli-Karjanmaa M, Szymkowski DE, Pierce DD, Lambertsen KL*, Bethea JR* (2014) Central versus peripheral administration of XPro1595 is therapeutic following moderate spinal cord injury. (*Co-corresponding and shared authors) J Neuroinflam 11:159.
3. Clausen BH, Degn M, Martin NA, Couch Y, Karimi L, Ormhøj M, Schmidt M-LB, Gredal HB, Gardiner C, Sargent IIL, Szymkowski DE, Petit G, Deierborg T, Finsen B, Anthony DC, Lambertsen KL (2014) Peripherally administered anti-TNF therapy ameliorates functional outcomes after focal cerebral ischemia. J Neuroinflam 11:203
4. Madsen PM, Clausen BH, Degn M, Thyssen S, Svensson M, Ditzel N, Finsen B, Deierborg T, Brambilla R, Lambertsen KL (2016) Genetic ablation of soluble TNF is associated with neuroprotection after focal cerebral ischemia. J Cereb Blood Flow Metab 36(9): 1553-1569.
5. Martin NA, Bonner H, Elkjær ML, D’Orsi B, Chen G, König HG, Svensson M, Deierborg T, Pfeiffer S, Prehn J, Lambertsen KL (2016) Deficiency of BID is partially neuroprotective in oxygen-glucose deprived organotypic hippocampal slice cultures, but not in a transient experimental stroke model. Front Cell Neurosci, Feb 3;10:14. doi: 10.3389/fncel.2016.00014.
6. Clausen BH, Lambertsen KL, Dagnaes-Hansen F, Babcock AA, von Linstow C, Meldgaard M, Kristensen BW, Wieloch T, Deierborg T, Finsen B (2016) Cell therapy centered on IL-1Ra is neuroprotective in experimental stroke. Acta Neuropathol 131(5):775-91.
7. Madsen PM, Mottie D, Karmally S, Szymkowski DE, Lambertsen KL, Bethea JR, Brambilla R (2016) Oligodendroglial TNFR2 mediates membrane TNF-dependent repair in neuroimmune disease by promoting oligodendrocyte differentiation and remyelination. J Neurosci 36:5128-5143.
8. Clausen BH, Degn M, Sivasaravanaparan M, Fogtmann T, Andersen MG, Trojanowsky M, Gao H, Hvidsten S, Baun C, Deierborg T, Finsen B, Kristensen BW, Bak S, Meyer M, Lee J, Nedospasov SE, Brambilla R, Lambertsen KL (2016) Conditional deletion of myeloid increases neuronal sensitivity to focal cerebral ischemia. Sci Rep, 6, 29291; doi: 10.1038/srep29291.
9. Ellman DG, Degn M, Christiansen ML, Clausen BH, Novrup HG, Flæng SB, Jørgensen LH, Suntharalingam L, Brambilla R, Lambertsen KL (2016) Genetic ablation of soluble TNF does not affect lesion size and functional recovery after moderate spinal cord injury in mice. Mediators of Inflamm, 2016:2684098. doi: 10.1155/2016/2684098.
10. Gao H, Danzi M, Choi C, Taherian M, Hansen CD, Ellman D, Madsen PM, Lemmon V, Lambertsen KL, Brambilla R (2016) Opposing functions of microglial and macrophagic TNFR2 in the pathogenesis of experimental autoimmune encephalomyelitis. Cell Reports, Jan 3;18(1):198-212. doi: 10.1016/j.celrep.2016.11.083.
Other outputs:
1. Lambertsen KL, Novrup HG, Bethea J, Bracchi-Ricard V (equal contributors) (2015) Methods of treating spinal cord injury. Patent No: WO/2016/040581, PCT/US2015/049360.
2. Lambertsen KL, Clausen BH, Finsen B, Nielsen HH, Finsen B (equal contributors) (2015) Fumaric acid derivatives for medical use. Patent No: WO2016074684 A1, PCT/DK2015/050344
3. Lambertsen KL, Clausen BH, Meyer M (equal contributors) (2015) Tnf-alpha inhibitor for treating stroke. Patent No: WO2016078672 A1, PCT/DK2015/050358
Key collaborations:
Danish:
Dr. Anders Bach, Department of Medicinal Chemistry, University of Copenhagen
Dr. Petrine Wellendorf, Experimental Pharmacology, University of Copenhagen
Dr. Karin Lykke-Hartmann, Department of Biomedicine, University of Aarhus
Dr. Allan Stensballe, Department og Health Science and Technology, Aalborg University
Dr. Søren Nielsen, Department of Health Science and Technology, Aalborg University
International:
Dr. Roberta Brambilla, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine.
Dr. Tomas Deierborg, Neuroinflammation, Lund University
Dr. Daniel Anthony, Department of Pharmacology, University of Oxford
Dr. Mathias Gelderblom, Department of Neurology, Hamburg University
Infrastructure:
The Lambertsen lab is fully equipped to perform animal models of spinal cord injury and stroke, including behavioral analysis, stereological, immunohistochemical, molecular and biochemical analyses, with specific focus on analysis of inflammatory pathways following CNS injury.