MPI for Heart and Lung Research
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Group leader: Nina Wettschureck

Project leaders: Denise Tischner, Harmandeep Kaur

PhD Students: Jorge Carvalho, Myriam Grimm

Technical Assistant: Karin Jäcklein.

The group of Nina Wettschureck is analyzing basic mechanisms of G-protein signaling in the cardiovascular and immune system. Using various in vitro techniques as well as conditional knockout mice, the group identified new functions for the G-protein families G12/13 and Gq/11 in the regulation of immune cells (1, 2), endothelial cells (3, 4), endocrine cells (5), and cardiomyocytes (6, 7). They furthermore showed that the G-protein-coupled receptor HCA2 crucially contributes to the therapeutic effect of dimethyl fumarate in neuroinflammation (8). Other ongoing projects focus on cellular transdifferentiation during atherosclerosis (9) and the mechanisms regulating cardiac fibroblast activation (10). New projects currently evolve based on single-cell expression analyses in primary murine vascular and immune cells. These analyses identified rare cell populations with specific GPCR repertoires; the role of these GPCRs in the regulation smooth muscle differentiation, endothelial activation, or regulation of T cell pathogenicity is currently under investigation.

Wettschureck group projects illustrated

Graphical overview over the topics addressed by the G-protein signaling group.


Selected references

  1. Grimm M, Tischner D, Troidl K, Albarran Juarez J, Sivaraj KK, Ferreiros Bouzas N, Geisslinger G, Binder CJ, and Wettschureck N. S1P2/G12/13 Signaling Negatively Regulates Macrophage Activation and Indirectly Shapes the Atheroprotective B1-Cell Population. Arterioscler Thromb Vasc Biol. 2016;36(1):37-48.

  2. Herroeder S, Reichardt P, Sassmann A, Zimmermann B, Jaeneke D, Hoeckner J, Hollmann MW, Fischer KD, Vogt S, Grosse R, Hogg N, Gunzer M, Offermanns S, Wettschureck N. Guanine nucleotide-binding proteins of the G12 family shape immune functions by controlling CD4+ T cell adhesiveness and motility. Immunity. 2009;30(5):708-20.

  3. Sivaraj KK, Takefuji M, Schmidt I, Adams RH, Offermanns S, and Wettschureck N. G13 controls angiogenesis through regulation of VEGFR-2 expression. Dev Cell. 2013;25(4):427-34.

  4. Sivaraj KK, Li R, Albarran-Juarez J, Wang S, Tischner D, Grimm M, Swiercz JM, Offermanns S, and Wettschureck N. Endothelial Galphaq/11 is required for VEGF-induced vascular permeability and angiogenesis. Cardiovasc Res. 2015;108(1):171-80.

  5. Sassmann A, Gier B, Grone HJ, Drews G, Offermanns S, and Wettschureck N. The Gq/G11-mediated signaling pathway is critical for autocrine potentiation of insulin secretion in mice. J Clin Invest. 2010;120(6):2184-93.

  6. Takefuji M, Kruger M, Sivaraj KK, Kaibuchi K, Offermanns S, and Wettschureck N. RhoGEF12 controls cardiac remodeling by integrating G protein- and integrin-dependent signaling cascades. J Exp Med. 2013;210(4):665-73.

  7. Takefuji M, Wirth A, Lukasova M, Takefuji S, Boettger T, Braun T, Althoff T, Offermanns S, and Wettschureck N. G13-mediated signaling pathway is required for pressure overload-induced cardiac remodeling and heart failure. Circulation. 2012;126(16):1972-82.

  8. Chen H, Assmann JC, Krenz A, Rahman M, Grimm M, Karsten CM, Kohl J, Offermanns S, Wettschureck N*, and Schwaninger M*. Hydroxycarboxylic acid receptor 2 mediates dimethyl fumarate's protective effect in EAE. J Clin Invest. 2014;124(5):2188-92. (*contributed equally)

  9. Albarran-Juarez J, Kaur H, Grimm M, Offermanns S, and Wettschureck N. Lineage tracing of cells involved in atherosclerosis. Atherosclerosis. 2016.

  10. Kaur H, Takefuji M, Ngai C, Carvalho J, Bayer J, Wietelmann A, Poetsch A, Holper S, Conway SJ, Mollmann H, Looso M, Troidl C, Offermanns S, Wettschureck N. Targeted Ablation of Periostin-Expressing Activated Fibroblasts Prevents Adverse Cardiac Remodeling in Mice. Circ Res. 2016.