 |
Kate Lykke Lambertsen Professor Department of Neurobiology Research Phone: 6550 3806 Alternative: 6550 3810
Email: klambertsen@health.sdu.dk
|
Research
-
In our laboratory we are studying cerebrovascular diseases of and trauma to the central nervous system, such as stroke and spinal cord injury (SCI) to try to understand the cellular and molecular mechanisms that contribute to 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 experimental stroke we use transgenic mouse models and other molecular approaches to study the central but complex role of the pleiotrophic, microglial-derived cytokine tumor necrosis factor (TNF) for neuronal survival/death. We have shown that TNF is present in low concentrations in normal brain tissue and that production of TNF by activated microglia is observed already 4 - 6 h after ischemia, which is within the ”therapeutic window” (4 - 4.5 h) in both mouse models of ischemic stroke and in the clinical setting. In combination with this, we have shown using a bone marrow chimeric approach that constitutively and/or early induced, presumably, microglial-derived TNF has a neuroprotective effect in experimental stroke. Taken together, this focuses our attention in the direction of studying the role of microglia in modulating neuronal sensititivity to ischemia.
To determine what role(s) trauma-induced inflammation plays in mediating secondary neuronal injury and cell death following SCI, we use transgenic mouse models and other molecular biological approaches. We specifically use transgenic mice that are deficient in neuronal NF-kB, which is a transcription factor that plays a pivotal role in regulating inflammation, and possibly apoptotic cell death pathways. In addition, we used mice that are display genetic modifications in their TNF expression and different anti-TNF therapies in order to try to identify novel neuroprotective therapeutics for treatment in SCI.
Our studies are performed in close collaboration with national and international collaborators.
Principal investigator
Kate Lykke Lambertsen graduated as a MSc from the University of Southern Denmark in 1999. She initiated her training in experimental neurobiology in the Department of Anatomy and Neurobiology, University of Southern Denmark, supervised by dr. Bente Finsen, when she was a master student. Following graduation in 1999 she became a PhD student in experimental neurobiology in the same department (maternity leave: December, 2001 – July, 2002). In 2004 she defended her PhD thesis entitled ”The patophysiological role of tumor necrosis factor and interferon gamma in focal cerebral ischemia in mice”. In 2005-2008 (maternity leave: March, 2005 – October, 2005) she did her first post doc funded by the Danish Medical Research Counsil at the Bente Finsen Laboratory, Medical Biotechnology Center, University of Southern Denmark. In 2008-09 she was a visiting scientist at the Miami Project to Cure Paralysis, in the laboratory headed by dr. John Bethea, funded by a grant from Carlsbergfondet. Upon her return to Odense, she was appointed an associate professor in Anatomy and Neurobiology at the Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark. Kate Lykke Lambertsen was a board member of the Danish Society for Neuroscience 2007-2011. Current sources of funding include the Lundbeck Foundation, the Danish MRC, the Danish Multiple Sclerosis Society.
Staff:
• PhD student Ditte Gry Ellman
• PhD student Pernille Marie Madsen
• PhD student Minna Yli-Karjanmaa
• MSc student Kira Stengaard Nielsen
• MSc student Lujitha Suntharalingham
• MSc student Minna Christiansen Lund
• Pregraduate MD student Camilla Dalby Hansen
• Pregraduate MD student Nagina Warraich
• Pregraduate MD student Simon Flæng
• BSc student Simone Dyring Hasselsteen
• BSc student Jonas Heinrich Vienhues
• BSc student Safinaz Dursun
• BSc student Emilie Boye Lester
• BSc student Sana Ilyas
• Technician Ulla Damgaard Munk
• Technician Dorte Lyholmer
Selected publications:
1. Lambertsen KL, Gregersen R, Drøjdahl N, Owens T and Finsen B (2001) A specific and sensitive method for visualization of tumor necrosis factor in the murine central nervous system. Brain Res Brain Res Protocols 7:175-191.
2. Lambertsen KL, Gregersen R, and Finsen B (2002) Microglial-macrophage synthesis of tumor necrosis factor after focal cerebral ischemia in mice is strain dependent. J Cereb Blood Flow Metab 22:785-797.
3. Lambertsen KL, Meldgaard M, Ladeby R, Finsen B (2005) A quantitative study of microglial-macrophage synthesis of tumor necrosis factor during acute and late focal cerebral ischemia. J Cereb Blood Flow Metab 25:119-136.
4. Lambertsen KL, Clausen BH, Fenger C, Wulf H, Owens T, Dagnæs-Hansen F, Meldgaard M, Finsen B (2007) Microglia and macrophages express TNF receptor p75 following middle cerebral artery occlusion in mice. Neuroscience 144:934-949.
5. Clausen BH, Lambertsen KL, Babcock A, Holm TH, Dagnæs-Hansen F, Finsen B
(2008) Interleukin-1β and tumor necrosis factor-a are expressed by different subsets of microglia and macrophages after ischemic stroke in mice. J Neuroinflam, 5:46 (23 October, 2008). (Shared first authorship).
6. 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.
7. Lambertsen KL, Deierborg T, Gregersen R, Clausen BH, Wirenfeldt M, Nielsen HH, Dalmau I, Diemer NH, Dagnaes-Hansen F, Johansen FF, Keating A, Finsen B (2011) Differences in origin of reactive microglia in bone marrow chimeric mouse and rat after transient global ischemia. J Neuropathol Exp Neurol 70:481-494.
8. Lambertsen KL, Biber K, Finsen B (2012) Inflammatory cytokines in experimental and human stroke. J Cereb Blood Flow Metab 32:1677-1698.
9. Lambertsen KL, Gramsbergen JB, Sivasaravanaparan M, Ditzel N, Sevelsted-Møller LM, Oliván-Viguera A, Rabjerg M, Wulff H, Köhler R (2012) Genetic KCa3.1-deficiency produces locomotor hyperactivity and alterations in cerebral monoamine levels. PLoSOne 7:e47744. Epub 2012 Oct 15.
10. Bracchi-Ricard V*, Lambertsen KL*, Ricard J, Nathanson L, Karmally S, Johnstone J, Ellman DG, Frydel B, McTigue D, Bethea JR (2013) Inhibition of astroglial NF-kB enhances oligodendrogenesis following spinal cord injury. (*Shared first authorship) J Neuroinflamm Jul 23;10(1):92.
11. Lambertsen KL, Østergaard K, Clausen BH, Hansen S, Stenvang J, Thorsen SB, Meldgaard M, Kristensen BW, Hansen PB, Sørensen GL, Finsen B (2014) Ablation of surfactant protein D in ischemic brain damage in mice. J Neuroinflam 11:123.
12. 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 senior authorship) J Neuroinflam 11:159.
13. 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.
14. Madsen PM, Clausen BH, Degn M, Thyssen S, Svensson M, Ditzel N, Finsen B, Deierborg T, Brambilla R, Lambertsen KL (2015) Genetic ablation of soluble TNF is associated with neuroprotection after focal cerebral ischemia. J Cereb Blood Flow Metab, Oct 19. pii: 0271678X15610339. [Epub ahead of print].
Book Chapters:
1. Lambertsen KL, Deierborg T (2012) A detrimental role of MIF in ischemic brain damage. In: The MIF Handbook, World Scientific Publishing Co. Editor: Richard Bucala,Yale University, pp. 361-377. (ISBN: 978-981-4335-35-5).
Applied methodologies, techniques and facilities
- Experimental models of stroke and spinal cord injury.
- Behavioral assessment of functional outcome following injury.
- Transgenic mouse models.
- Molecular and cellular techniques: Quantitative real-time PCR, Elisa, Western blotting, in situ hybridization, immunohistochemistry, flow cytometry, fluorescence staining and double labelings, histochemistry, stereologi, volume estimations.
International and national collaboration:
1. Dr. Tomas Deierborg, Department of Experimental Medical Science, University of Lund.
2. Dr. Daniel Anthony, Department of Pharmacology, University of Oxford.
3. Dr. Sofia Duque Santos, Institute for Molecular and Cell Biology, University of Porto.
4. Dr. Roberta Brambilla, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine.
5. Dr. Jochen Prehn, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland
6. Dr. Mette Berendt, LIFE, University of Copenhagen
7. Dr. Karin Lykke-Hartmann, Department of Biomedicine, University of Aarhus
8. Dr. Kristian Strømgaard and Dr. Anders Bach, Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen
9. Dr. David Szymkowski, Xencor Inc, Monrovia, CA
10. Dr. Kim Ryan Dragsbek, CFIN, University of Aarhus
11. Dr. Søren Nielsen and Dr. Allan Stensballe, Department of Health Science and Technology, Aalborg University