Compartmentation of cardiac signaling
We investigate treatment of heart failure
Heart failure (HF) represents a major societal and personal burden. Broadly, there are two types of HF:
- HFrEF, with a dilated ventricle and reduced systolic function displaying reduced ejection fraction (EF)
- HFpEF, with a stiff heart with concentric hypertrophy, displaying reduced diastolic function and preserved ejection fraction
Treatment for HFrEF includes ACE-inhibitors, angiotensin receptor blockers, SGLT2-inhibitors, spironolactone and β-blockers, whereas effective treatment for HFpEF so far is restricted to certain subgroups of patients.
Our research group is investigating the spatial and temporal signalling through cyclic GMP (cGMP) and cyclic AMP (cAMP), by using FRET-based biosensors localized to specific intracellular compartments in cardiac myocytes.
We have a particular emphasis on the role of nitric oxide, natriuretic peptides, beta-adrenergic and 5-HT4 serotonin receptors - with the aim to unravel signalling mechanisms that contribute to improving HFpEF in animal models.
To determine if treatment targeting these signalling pathways is effective in HF, we perform both short- and long-term treatment of HFpEF and HFrEF in animal models.
- Development of biosensors for cGMP
Compartmentation of cAMP and cGMP signalling in normal and failing hearts
- Develop novel therapeutic targets for HFpEF and HFrEF
- Spatial and temporal understanding of receptor-G protein interactions
- Manuela Zaccolo, University of Oxford, UK
- Viacheslav Nikolaev, University Medical Center Hamburg-Eppendorf, Germany
- Choel Kim, Baylor college of medicine, TX, USA
- David Paterson, University of Oxford, UK
- Nevin Lambert, Augusta University, GA, USA
- Moritz Bünemann, Philipps-Universität Marburg, Germany
- Martin Lohse, Max Delbrück center for molecular medicine, Germany
- Kees Jalink, Netherlands Cancer Institute, Netherlands
- Gunnar Schulte, Karolinska institutet, Sweden