Scientific Profile of Collaborative Research Center SFB 1002 (2016-2020)

Summary of the Research Program

Cardiac insufficiency or heart failure represents one of the gravest medical and socio-economical challenges of the 21st century. So far, all pharmacological therapies that improve symptoms and prognosis rely on the global inhibition of neurohumoral activation of the heart. We refer to the functional cellular and intercellular entities that are putative novel therapeutic targets as modulatory units. During the first funding period, we have developed mouse models of preload and afterload to study such modulatory units, and a number of treatment targets have been identified. Some of these are already in the translational pipeline to first in man studies.

However, the urgent need for novel therapeutic principles in addition to neurohumoral regulation persists, and the CRC 1002 continues to be devoted to developing such therapeutic strategies in heart failure. Based on the advances during the first funding period, the many interactions between CRC 1002 groups, and input by principal investigators recently recruited to Göttingen, we have focused on a new overarching problem, the transition from structural heart disease to failure. Experimental strategies to tackle this process include new animal models to address the impact of epigenetics on the transition and a transition biobank of pertinent human samples.

The career development program of the Heart Research Center Göttingen (HRCG) and a close relationship of CRC 1002 with the thematically complementary graduate program (IRTG1816: Phosphorylation- and Redox-dependent signal mechanisms in the diseased heart) offers great research opportunities and highly targeted graduate training to junior scientists.

Two conceptual approaches are key to building and further developing the active network of basic and clinical scientists in CRC 1002 during the new funding period: (1) The molecular analysis of cellular and intercellular pathways in cardiomyocytes and other cardiac cell types and (2) a focus on the distinct transition phases underlying the development of heart failure over time. Both approaches are applied to all three research areas, i.e. to gene regulation, to the spatial organization of signal transduction into nano- and microdomains as well as to cell-to-cell interactions.

The results of the first funding period, the research infrastructure consolidated and extended during this time, and the visibility of CRC 1002 project leaders in the international field of molecular and clinically relevant cardiac research will allow us to contribute further advances to this field