(November 2011) During her PhD theses Julia Brandmayr studied the role of the Ca_vβ₂ protein C-terminus in the regulation of the voltage activated calcium channel complex Ca_v1.2 in the cardiovascular system. Several predicted phosphorylation sites on the carboxy terminus of the Ca_vβ₂ protein have shown a crucial impact on L-type calcium currents in vitro. Julia Brandmayr has generated knock-in mice and analyzed the impact of these sites in vivo.

(October 2011) Dr. Antonio Sarikas and his students Barbara Zollner and Christoph Berg (PJ Wahlfach Pharmakologie) were honored for "outstanding achievements in medical education" at the annual conference of the German Association for Medical Education (GMA) in Munich. The group initiated  www.pharmacases.de, a novel elearning website of clinical pharmacology.

(August 2011) Drugs that activate the β₂-adrenergic receptor (β₂AR), or β₂AR agonists, are used to treat various conditions, such as asthma and premature labor contractions. Frequently occurring polymorphisms that result in amino acid substitutions at position 16 in the β₂AR have been correlated to different responses to these drugs. Ahles et al. found that the β₂AR responded differently to repeated drug stimulation, a phenomenon the authors call receptor "memory." A variant of the β₂AR with arginine at position 16 was slower in response to repeated stimulation. In contrast, a polymorphic variant of β₂AR with glycine at position 16 showed faster activation when repeatedly stimulated, an effect that was associated with increased production of a downstream signaling molecule. The authors propose that these polymorphism-specific responses of the β₂AR to continued stimulation may contribute to individual variation in responses to β₂AR agonists (Editor's summary of this article).

Ahles A, Rochais F, Frambach T, Bünemann M, Engelhardt S. A Polymorphism-Specific "Memory" Mechanism in the β₂-Adrenergic Receptor. Sci. Signal. 4, ra53 (2011).

(August 2011) The cardiac muscle responds to mechanical and humoral stress by hypertrophic growth of individual myocytes. Although some degree of cardiac hypertrophy serves to reduce wall stress and helps to compensate for increased load on the myocardium, sustained prohypertrophic signaling within cardiomyocytes is clearly detrimental and a major factor contributing to the progression to failure. The activation of Ca2+-dependent signaling pathways has been identified as critical for cardiac hypertrophy. However, it has remained largely unclear how Ca2+ triggers signaling in cardiac myocytes in the presence of the rapid and large Ca2+ fluctuations that occur during excitation contraction coupling. Here, we have studied the role of stromal interaction molecule 1 in cardiomyocytes, a molecule that has been described in several cell types as critical for Ca2+ entry. By manipulating its expression, we found stromal interaction molecule 1 to be both sufficient and necessary for cardiomyocyte hypertrophy in vitro and in the adult heart in vivo. Stim1 silencing by viral gene transfer protected rats from pressure overload–induced cardiac hypertrophy. These data demonstrate an important role for stromal interaction molecule 1 in cardiac hypertrophy and may lead to the development of novel approaches to prevent cardiac dysfunction.

Hulot JS, Fauconnier J, Ramanujam D, Chaanine A, Aubart F, Sassi Y, Merkle S, Cazorla O, Ouille A, Dupuis M, Hadri L, Jeong D, Muehlstedt S, Schmitt J, Braun A, Benard L, Saliba Y, Laggerbauer B, Nieswandt B, Lacampagne A, Hajjar R, Lompre AM, and Engelhardt S. A critical role for STIM1 in cardiac hypertrophy. Circulation. 124(7):796-805 (2011).

(July 2011) On July 21st/22nd, the Institute of Pharmacology and Toxicology (TUM), Munich will host the 3rd Meeting of the Transatlantic Network of Excellence on MicroRNAs as therapeutic targets in heart failure. Coordinated by Stefan Engelhardt and Eric Olson (Dallas), this research consortium aims to translate insights from basic research into novel therapeutic strategies.  The meeting will be held at Schloss Hohenkammer and includes the second year review of the network through international reviewers.

(July 2011) MicroRNAs (miRNAs) are small non-coding RNAs that control expression of complementary target mRNAs. A growing number of miRNAs has been implicated in the pathogenesis of cardiac diseases, mostly based not on functional data, but on the observation that they are dysregulated in diseased myocardium. Consequently, our knowledge regarding a potential cardiac role of the majority of miRNAs is limited. Claudia Jentzsch and colleagues now report the development of an assay format that allows the simultaneous analysis of several hundred molecules with regard to their phenotypic effect on primary rat cardiomyocytes. Using automated microscopy and an edge detection algorithm, they identified novel miRNAs regulating cardiomyocyte hypertrophy.

Jentzsch C, Leierseder S, Loyer X, Flohrschütz I, Sassi Y, Hartmann D, Thum T, Laggerbauer B, and Engelhardt S. A phenotypic screen to identify hypertrophy-modulating microRNAs in primary cardiomyocytes. J Mol Cell Cardiol. In press (2011).

(July 2011) Dr. Antonio Sarikas was awarded a four year Marie Curie Grant (IRG) by the European Commission to support his professional reintegration to Germany. Dr. Sarikas was a researcher at the Mount Sinai School of Medicine (New York City, USA) from 2006 to 2009. Since September 2009 he is an group leader at the at the Institute of Pharmacolocgy and Toxicology. His research focuses on the role of the ubiquitin-proteasome system (UPS) in cell signaling and diseases mechanisms.

(April 2011) Andrea Ahles received a Poster Award (1st place) at the 9th Dutch-German Joint Meeting of Molecular Cardiology Working Groups 2011 in Ulm for her work entitled “A polymorphism-specific memory mechanism in the ß2-adrenergic receptor“.