The lab: Gotthardt group

Max Delbrück Center for Molecular Medicine

We are interested in understanding how alternative splicing relates to diastolic heart failure, how increased filling of the cardiac ventricle leads to improved contraction. Our main translational focus is on harnessing alternative splicing to improve cardiac function using a pharmacological screen with custom splice reporter assays. This work aims to identify and characterize patients with splice related heart disease towards improved personalized diagnostics and therapy. The group consists of Groupleader MD, Technicians, Postdocs, PhD students, Master students of different nationalities (Germany, Spain, India, Indonesia) with ~50% male/female balance. The lab closely collaborates with the department of Cardiology on heart faiure with preserved ejection fraction (HFpEF) – Prof. Burkert Pieske and Prof. Frank Heinzel.

Country: Germany
Supervisor: Michael Gotthardt
Research group website

The position

Cardiovascular disease remains the primary cause of death in the developed world. Notwithstanding improved prevention and therapy, the prevalence of heart failure continues to rise. The role of alternative splicing in cardiovascular disease has only recently been appreciated, with mutations in the splice factor RBM20 associated with particularly severe cardiac phenotypes, including early-onset sudden cardiac death.

Translating our findings to improve patient care, we will study (1) how alternative splicing is regulated in the heart, (2) how it contributes to cardiac adaptation in perinatal development versus myocardial disease and (3) how exon-level information across RNA species can be obtained, analyzed, and leveraged to improve personalized diagnosis of heart disease. Thus, we will evaluate how the cardiac splice regulatory network can be mined for novel therapeutic targets and utilized for the development of novel therapeutic approaches to cardiac disease.

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