Group name: Clausen Group
Group leader: Bettina Hjelm Clausen
Group members: Technicians: 1, Phd students: 1, Master students: 2.
Department & University/Hospital/Other: Department of Neurobiology Research, Dapartment of Molecular Medicine, SDU
Funding sources: Hørslev Fonden, Carlsbergfondet, Lundbeck Foundation, Fonden for Lægevidenskabens Fremme. Brødrene Hartmanns Fond.
Description of research:
Targeted drug-delivery has so far failed in stroke patients, causing our group to establish a new tech-nology platform which will allow us to target and understand why the body´s own immune cells is superior to drug therapies in regulating and fighting inflammation following ischemic stroke. We aim to decipher the impact of cellular cross-talk in order to develop new anti-inflammatory treatment strategies applicable in the acute phase after stroke onset and identify new target proteins, which can be used diagnostically, in a disease where time is brain. Increased knowledge about the functional diversity of immune cells will provide us with a better understanding of the inflammatory response in acute, chronic and/or inflammatory CNS disorders.
Our area of research interests:
• To understand the interplay between the peripheral immune system and the CNS following stroke.
• To stimulate a favorable inflammatory response in the brain post-stroke and thereby achieve neu-roprotection.
• To direct innate microglia, situated at the site of injury, as modulators of neuroprotection.
• To study and understand the mechanism(s) responsible for stimulating the production of neuro-protective cytokines in monocytes.
Key publications (last 10 years):
Clausen BH, Lundberg L, Yli-Karjanmaa M, Martin NA, Svensson M, Alfsen MZ, Flaeng SB, Lyngsø K, Boza-Serrano A, Nielsen HH, Hansen PB, Finsen B, Deierborg T, Illes Z, Lambertsen KL (2017). Fumarate decreases edema volume and improves functional outcome after experimental stroke. Experimental Neurology 295:144-154.
Grønhøj MH, Clausen BH, Fenger C, Lykke Lambertsen K, Finsen B (2017). Beneficial potential of intravenously administered IL-6 in improving outcome after murine experimental stroke. Brain Behavior and Immunity pii: S0889-1591(17)30165-4.
Clausen BH, Degn M, Sivasaravanaparan M, Fogtmann T, Andersen MG, Trojanowsky MD, Gao H, Hvidsten S, Baun C, Deierborg T, Finsen B, Kristensen BW, Bak ST, Meyer M, Lee J, Nedospasov SA, Brambilla R, Lambertsen KL (2016). Conditional ablation of myeloid TNF increases lesion volume after experimental stroke in mice, possibly via altered ERK1/2 signaling. Scientific Reports 6:29291.
Clausen BH, Lambertsen KL, Dagnæs-Hansen F, Babcock AA, Linstow CU, Meldgaard M, Kristensen BW, Deierborg T, Finsen B. Cell therapy centered on IL-1Ra is neuroprotective in experimental stroke (2016). Acta Neuropathologica 131:775-791.
Venø MT, Hansen TB, Venø ST, Clausen BH, Grebing M, Finsen B, Holm IE, Kjems J (2015). Spatio-temporal regulation of circular RNA expression during porcine embryonic brain development. Genome Biology 16:245.
Clausen B, Degn M, Martin N, Couch Y, Karimi L, Ormhøj M, Mortensen ML, Gredal H, Gardiner C, Sargent II, Szymkowski DE, Petit GH, Deierborg T, Finsen B, Anthony D, Lambertsen K (2014). Systemically administered anti-TNF therapy ameliorates functional outcomes after focal cerebral ischemia. Journal of Neuroinflammation 11:203.
Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J. Natural RNA circles function as efficient miRNA sponges (2013). Nature 495:384-388.
Bach A, Clausen BH, Møller M, Vestergaard B, Chi CN, Round A, Sørensen PL, Nissen KB, Kastrup JS, Gajhede M, Jemth P, Kristensen AS, Lundström P, Lambertsen LK, Strømgaard K (2012). A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage. Proc Aatl Acad Sci U S A 109:3317-3322.
Lambertsen KL, Clausen BH, Babcock AA, Gregersen R, Fenger C, Nielsen HH, Haugaard LS, Wirenfeldt M, Nielsen M, Dagnaes-Hansen F, Bluethmann H, Faergeman NJ, Meldgaard M, Deierborg T, Finsen B (2009). Microglia protect neurons against ischemia by synthesis of tumor necrosis factor. Journal of Neuroscience 29:1319-1330.
Clausen BH, Lambertsen KL, Babcock AA, Holm TH, Dagnaes-Hansen F, Finsen B (2008). Interleukin-1β and tumor necrosis factor-alfa are expressed by different subsets of microglia and macrophages after ischemic stroke in mice. Journal of Neuroinflammation 5:46.
Other outputs:
1. Lambertsen KL, Clausen BH, Finsen B, Nielsen HH, Finsen B (equal contributors) (2014) Fumaric acid derivatives for medical use, Application No. 62/078,051, filed 11/11-2014.
2. Lambertsen KL, Clausen BH, Meyer M (equal contributors) (2014) Compositions and methods for treating stroke, Application No. PA 2014 70728, filed 20/11-2014.
Key collaborations:
Danish:
Dr. Jørgen Kjems, Department of Molecular Biology, University of Aarhus.
Dr. Kristian Strømgaard, Department of Medical Chemistry, University of Copenhagen.
Dr. Anders Bach, Department of Medical Chemistry, University of Copenhagen.
Dr. Harald S. Hansen, Department of Drug Design and Pharmacology. University of Copenhagen.
Dr. Allan Stensballe, Department of Health Science and Technology, Aalborg University.
Dr. Søren Nielsen, Department of Health Science and Technology, Aalborg University.
Dr. Bjarne Winther Kristensen, Pathology Institut, Odense Universitets Hospital.
International:
Dr. Stuart Cordwell, School of Molecular Bioscience, University of Sydney.
Dr. Daniel Anthony, Experimental Neuropathology Laboratory, University of Oxford.
Dr. Tomas Deierborg, Department of Experimental Medical Science, Lund University.
Dr. Mathias Gelderblom, Department of Neurology, Hamburg University.
Dr. Tomas Bjӧrklund, Molecular Neuromodulation, Wallenberg Neuroscience Center, Lund University.
Dr. Roberta Brambilla, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine.
Dr. Sofia Santos, NanoBiomaterials for Targeted Therapies, University of Porto.
Infrastructure:
Experienced in experimental stroke research, cellular isolation and post-stroke transplantation techniques as well as behavioural testing. Basic laboratory skills include immunohistochemistry, in situ hybridization, qPCR, ELISA, Western Blotting and MACS cell separation technology. Proteomics and Flow-cytometry are routinely performed on a collaborative basis.
Equipment available: gentleMACS Dissociator and Cell Separator.