Alicia Llorente: Urinary extracellular vesicles as a source of noninvasive prostate cancer biomarkers
Abstract: Circulating tumor cells and circulating tumor DNA and proteins have been the most commonly structures analyzed as cancer biomarkers in liquid biopsies. Recently, extracellular vesicles shed from tumors have also started to be analyzed. Extracellular vesicles are indeed found in most human biofluids, and have a diverse molecular cargo (proteins, nucleic acids such as mRNA and miRNA, lipids, metabolites) that represents the status of the tissue of origin. Currently, urine is the biofluid of choice in many studies that aim at identifying new noninvasive biomarkers for urological diseases. In the last years my group has been investigating the usefulness of urinary EV molecules as biomarkers for prostate cancer. In this seminar recent results on this topic will be presented.
Magnus Aronsen: Regulation of cardiac function by cAMP signalosomes: PDE2 inhibitors as novel antitherapeutic target?
Abstract: Cardiac contractility is regulated by calcium fluxes, and many central ion channels and transporters in cardiomycoytes have been documented to be regulated by localized cAMP signalling events orchestrated by A-kinase anchoring proteins (AKAPs). AKAPs couple protein kinase A (PKA) to specific substrates, which often co-localizalization of AKAPs with phosphodiesterases (PDEs) that limits cAMP influx into the local signalling domain. In an ongoing effort to identify activators of the Na+/K+-ATPase (NKA), believed to be the upstream event in some types of ventricular tachykardia, we found that PDE2 seems to exclusively regulate PKA-activity in the NKA domain without other effects on cardiac contractility. We have mapped a specific NKA-PKA RII-AKAP-PDE2 interactome, and further observed that PDE2 inhibitors have a potent anti-arrhythmic effect in mice models of cardiac arrhythmias. We believe that selective activation of the NKA by PDE2 inhibitors offer a novel strategy to prevent ventricular tachykardias i selected patients.