SFB 1470:  Multilevel mechanistic characterisation of Heart Failure with Preserved Ejection Fraction - Towards a novel classification of HFpEF for targeted therapies

Subject Area Medicine
Biology
Computer Science, Systems and Electrical Engineering
Term since 2022
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 437531118
 

Project Description

The prevalence of heart failure (HF) is increasing and morbidity and mortality are unacceptably high. Diagnosis and clinical management of HF are currently guided by left ventricular ejection fraction (LVEF), as HF with preserved ejection fraction (HFpEF) is considered a distinct disease than HF with reduced ejection fraction (HFrEF). In HFrEF, treatment strategies have been developed to improve prognosis, but they have proven ineffective in HFpEF, so that we are still unable to offer specific therapies to this large subset of HF patients (~50%). In this CRC, we follow an interdisciplinary approach from organism to organ to cell to molecule towards characterizing HFpEF as a systemic and heterogeneous disorder. Our central hypothesis is that dysregulation of systemic hemodynamic, metabolic and inflammatory pathways contributes to distinct HFpEF phenotypes with specific pathophysiological features, which differentially respond to targeted therapies. Leveraging our expertise in multi-omics, advanced imaging, functional phenotypic analysis, AI and modeling, will provide an improved basis for a comprehensive mechanistic understanding of the disorder to guide innovative therapies to the individual patient.We have designed our research program around defined mechanical, metabolic, inflammatory, and immunological triggers, their respective downstream signaling pathways and specific cardiac response patterns. We connect young and established basic scientists and clinicians with expertise in translational cardiology, functional genomics, cell and molecular biology, systems medicine, proteomics, metabolomics and bioinformatics to towards improved deep phenotyping and classification of HFpEF in relevant animal models and patients as a basis for individualized therapy.We emphasize training the next generation of heart failure researchers, focusing on good scientific practice, equal opportunities, patient involvement and the principles of 3R to foster a culture of cooperation, communication and cross-topic activity. Together, we will provide the basis for an improved mechanistic understanding and classification of HFpEF that combines advanced imaging, multi-omics and classical risk factor analysis, thereby building the foundation for causal, individualized therapies. We believe that our approach will be instrumental to improving the management of HFpEF as one of medicine´s largest unmet clinical needs.
DFG Programme Collaborative Research Centres

Current projects

Applicant Institution shared FU Berlin and HU Berlin through:
Charité - Universitätsmedizin Berlin
Participating University Medizinische Hochschule Hannover
Participating Institution Charité - Universitätsmedizin Berlin
Deutsches Herzzentrum der Charité (DHZC); Max-Delbrück-Centrum für Molekulare Medizin (MDC)
Co-Applicant Institution Freie Universität Berlin; Humboldt-Universität zu Berlin
Spokespersons Professor Dr. Michael Gotthardt, since 11/2022; Professor Dr. Burkert Pieske, until 11/2022