Principal Investigator: Prof. Dr. rer. nat. Susanne Lutz
The research of our group focuses on G protein-dependent signaling in cardiac cells. We intend to identify signal cascades and mechanisms being involved in the pathology of heart diseases. This includes GPCR-driven signaling like the regulation of calcium handling in cardiac fibroblasts and its impact on protein secretion and thus in fibrotic processes.
We are studying in addition the functions of guanine nucleotide exchange factors especially of the p63RhoGEF family, of RhoGTPases and their downstream effectors ROCK 1 and 2 in different cardiac cells with in vivo as well as in vitro models to identify their role in cardiac hypertrophy and fibrosis.
Our methodological repertoire includes heart disease mouse models with subsequent analyses e.g. echocardiography, primary cell isolations from neonatal and adult animals, 3D culture models of homo- and heterogeneous cell populations, functional testing of 3D cultures including rheology and contraction measurements, viral gene delivery, life cell imaging, confocal imaging and several biochemical and molecular methods.
Wuertz CM, Lorincz A, Vettel C, Thomas MA, Wieland T, Lutz S. (2010) p63RhoGEF-a key mediator of angiotensin II- dependent signaling and processes in vascular smooth muscle cells. FASEB J.; 24(12): 4865-76. [PubMed]
Shankaranarayanan A, Boguth CA, Lutz S, Vettel C, Uhlemann F, Aittaleb M, Wieland T, Tesmer JJ. (2010) Galpha(q) allosterically activates and relieves autoinhibition of p63RhoGEF. Cell Signal.; 22(7): 1114-23. [PubMed]
Lutz S, Shankaranarayanan A, Coco C, Ridilla M, Nance MR, Vettel C, Baltus D, Evelyn CR, Neubig RR, Wieland T, Tesmer JJ. (2007) Structure of Gaq-p63RhoGEF-RhoA complex reveals a pathway for activation of RhoA by GPCRs. Science; 318(5858): 1923-7. [PubMed]
Williams S, Lutz S, Charlie N, Vettel C, Ailion M, Coco C, Tesmer JJG, Jorgensen E, Wieland T, Miller K. (2007) Trio’s Rho-specific GEF domain is the missing Gaq effector in the C. elegans synaptic signalling network. Genes Dev.; 21(21): 2731-46. [PubMed]
Lutz S, Freichel-Blomquist A, Yang Y, Ruemenapp U, Jakobs KH, Schmidt M, Wieland T. (2005) The guanine nucleotide exchange factor p63RhoGEF, a specific link between Gq/11-coupled receptor signaling and RhoA. J Biol Chem.; 280(12): 11134-9. [PubMed]
Ongherth A, Pasch S, Wuertz CM, Nowak K, Kittana N, Weis CA, Jatho A, Vettel C, Tiburcy M, Toischer K, Hasenfuss G, Zimmermann WH, Wieland T, Lutz S. (2015) p63RhoGEF regulates auto- and paracrine signaling in cardiac fibroblasts. J Mol Cell Cardiol 88: 39-54. [PubMed]