Unequal allelic expression (from cell to cell) as a pathomechanism for Hypertrophic Cardiomyopathy




Dr. Judith Montag

Institut für Molekular- und Zellphysiologie

Carl-Neuberg-Straße 1

30625 Hannover

Office     I03-floor 1 - level 03 – room 1340

Telephone    (+49) 511 532 2094
Fax              (+49) 511 532 4296
E-Mail          Dr. rer. nat. Judith Montag




Research focus

We examine the unequal expression of wildtype and mutant alleles in heterozygous patients with hypertrophic cardiomyopathy (HMC) as a potenial pathomechanism.

In previous work in our department, we could show that force generation differs severely between cardiomyocytes from the very same patient at the same calcium concentration. We hypothesized that this functional heterogeneity between neighboring cardiomyocytes may disrupt the myocardial network. This may lead to hallmarks of HCM such as cardiomyocyte and myofibrillar disarray, hypertrophy and fibrosis („contractile imbalance hypothesis).

The special focus of our research group are the molecular mechanism underlying the contractile imbalance. We analyse the allele specific mRNA expression in single cardiomyocytes from cryosections of HCM patients and heart-healthy controls and in human induced pluripotent stem cells. We could show that individual cardiomyocytes express highly divergent fraction of mutant per wildtype mRNA. In addition, we visualize active transcription sites in individual nuclei to examine whether burst-like transcription, a stochastic and independent on and off switch of the alleles, may cause the allelic imbalance from cell to cell. To enable a longitudinal analysis of contractile imbalance and the underlying mechanisms and to test potential therapeutic approaches, we apply CRIPSR/Cas9 to to generate a genome edited pig model for HCM.