Myocardial Genetics
Trends in Cardiovascular Medicine, January 2012, Vol. 22, Issue 1
Professor Ralph Knöll, Head of Group
The group's main focus is on the analysis of cardiac mechanosensation.
Mechanosensation is the initial process leading to the conversion of any change in cell shape and structure into biochemical signals. Previously we have been able to identify the muscle LIM protein (MLP) together with telethonin (TCAP) and titin as a macromolecular complex involved in mechanosensation in cardiomyocytes.
However, not all aspects of cardio-mechanosensation can be explained by this signalosome alone, additional proteins have to be present in this complex and other mechanisms of mechanosensation are certainly involved as well.
Circulation Research, March 2010, Vol. 106, Issue 1
As a consequence, we are interested in novel MLP interacting proteins, which we identified via a yeast two hybrid screen.
The group also has a major interest in the genetic basis of human heart failure and cardiomyopathy.
Therefore we analyse the following aspects:
- Relevance of human mutations in genes involved in cardiac mechanosensation
- Detection and analysis of novel human disease genes
-
New therapeutic approaches to treat cardiomyopathy and heart failure (kinase inhibitors, calcineurin or phosphatase inhibitors)
- Structural analysis of new components involved in mechanosensation (new yeast two hybrid screens)
- Zebrafish analysis (fast approach regarding in vivo function)
- Generation and analysis of novel genetically altered mouse models
- Epigenetics of mechanosensation
- Mechanosensation and diastolic dysfunction
- Interactom, Proteom and Proteomics of mechanosensation
Epifluorescent microscopy of the W4R-MLP knock in myocardium (Knöll et al., Circ Res 2009)
Selected Publications
Knöll R and Marston, S (27 Jul 2012). On Mechanosensation, Acto/Myosin Interaction, and Hypertrophy. Trends Cardiovasc Med. 22(1):17-22
Knöll R, Linke WA, Zou P, Miocic S, Kostin S, Buyandelger B, Ku CH, Neef S, Bug M, Schäfer K, Knöll G. (28 Jul 2011). Telethonin Deficiency Is Associated With Maladaptation to Biomechanical Stress in the Mammalian Heart. Circ Res. 109(7):758-69
Knöll R; Kostin S; Klede S; Savvatis K; Klinge L; Stehle I; Gunkel S; Kötter S; et al. (31 Dec 2009). A Common MLP (Muscle LIM Protein) Variant Is Associated With Cardiomyopathy. Circ Res. 106(4):695-704
Knöll R; Postel R; Wang J; Krätzner R; Hennecke G; Vacaru AM; Vakeel P; Schubert C; et al. (31 Jul 2007). Laminin-alpha4 and integrin-linked kinase mutations cause human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells. Circulation. 116:515-525
Knöll R; Hoshijima M; Hoffman HM; Person V; Lorenzen-Schmidt I; Bang ML; Hayashi T; Shiga N; et al. (27 Dec 2002). The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell. 111:943-955
