P2: cGMP signaling in cardiac injury and repair

• Assess Cre/lox-based cell-specific mutants with perturbed cGMP signaling in myocardial infarction and cardiac arrest and cardiopulmonary resuscitation models of cardiac damage.
• Define the potential of cGMP-based drugs (as well as H2S or inhaled NO) in treating or preventing heart dysfunction, adverse remodelling events and mortality in post-myocardial infarction and post-cardiac arrest and cardiopulmonary resuscitation mice.
• Determine whether ex-vivo or intravital FRET-based microscopy approaches allow us to measure the response of cGMP signals to pharmacological modulators in myocardial infarction and cardiac arrest at the cellular, whole organ or animal level.
• Finally, studies on animal models of cardiac damage will be corroborated by ex vivo experiments analyzing the impact of these events on primary cell functions. We aim to dissect the molecular mechanism(s) that differentially modulate the remodeling as well as immunological reactions and pump functions after e.g. cardiac arrest or myocardial infarction.

In the Ichinose lab in Boston, the doctoral researchers will be trained in

1. the cardiac arrest and cardiopulmonary resuscitation model (CA/CPR),
2. different invasive and non-invasive methods for assessing right (and left) ventricular function, and
3. the therapeutic application of inhaled nitric oxide.

In a first step, they will also attempt to prove the translational potential of our animal based work by testing promising cGMP-elevating drugs (which will be made available by Bayer and Ironwood) in failing human cardiomyocytes and non-cardiomyocytes, which are available in the Ichinose lab. Following the technical guidance in Boston, CA/CPR experiments will then be performed in cell-type specific mutants.

Prof. Fumito Ichinose MD, PhD

Link to boston researcher lab