10 | Brain macrophages in the remodelling of microvessels

Cerebral small vessel diseases are characterized by rarefaction of capillaries and loss of endothelial cells. Under which conditions angiogenesis is able to compensate for the loss of vessels is still largely unclear. We have established a mouse model of small vessel disease that is associated with a strong pro-angiogenic response. In this model we will study the modulation of angiogenesis by macrophages. For this purpose we will employ state-of-the-art pharmacological and genetic tools. We will profile the transcriptome at the single cell level and will use CRISPR-Cas9 technology for the inducible in vivo inhibition of signalling cascades that mediate the effect of macrophages on endothelial cells.

Publications

  • Müller-Fielitz H, Stahr M, Bernau M, Richter M, Abele S, Krajka V, Benzin A, Wenzel J, Kalies K, Mittag J, Heuer H, Offermanns S, Schwaninger M. Tanycytes control the hormonal output of the hypothalamic-pituitary-thyroid axis. Nat Commun 2017;8:484.
  • Dogbevia GK, Tollner K, Körbelin J, Broer S, Ridder DA, Grasshoff H, Brandt C, Wenzel J, Straub BK, Trepel M, Loscher W, Schwaninger M. Gene therapy decreases seizures in a model of Incontinentia pigmenti. Ann Neurol 2017;82:93-104.
  • Körbelin J, Dogbevia G, Michelfelder S, Ridder D, Hunger A, Wenzel J, Seismann H, Lampe M, Bannach J, Pasparakis M, Kleinschmidt J, Schwaninger M*, Trepel M*. A brain microvasculature endothelial cell-specific viral vector with the potential to treat neurovascular and neurological diseases. EMBO Mol Med 2016;8:609-625 (*these authors contributed equally to this work).
  • Ridder DA*, Wenzel J*, Müller K, Töllner K, Tong X-K, Assmann JC, Stroobants S, Weber T, Niturad C, Fischer L, Lembrich B, Wolburg H, Grand’Maison M, Papadopoulos P, Korpos E, Truchetet F, Rades D, Sorokin LM, Schmidt-Supprian M, Bedell BJ, Pasparakis M, Balschun D, D’Hooge R, Löscher W, Hamel E, Schwaninger M. Brain endothelial TAK1 and NEMO safeguard the neurovascular unit. J Exp Med 2015;212:1529-1549 (*these authors contributed equally to this work).
  • Chen H, Assmann JC, Krenz A, Rahman M, Grimm M, Karsten CM, Köhl J, Offermanns S, Wettschureck N*, Schwaninger M*.) Hydroxycarboxylic acid receptor 2 mediates dimethyl fumarate’s protective effect in EAE. J Clin Invest 2014;124: 2188-2192 (*these authors contributed equally to this work).


Potential secondments

IEMHAS (Ádám Dénes), month 8-9; POLYGENE (Doron Shmerling), month 16-18; UKLFR (Marco Prinz), month 23-25.

Host Organisation:
Institute for Experimental and Clinical Pharmacology and Toxicology , University of Lübeck, Germany
Supervisor:
Markus Schwaninger