Signal Transduction

PI:  
Prof. J. Prickaerts, PhD

Research Staff:   
Prof. Y. Temel, MD, PhD, Prof. F. Verhey, MD, PhD, Prof. M. De Baets, MD, PhD, P. Aalten, PhD, D. van den Hove, PhD, Prof. B. Rutten, MD, PhD

Postdocs:       
N. van Goethem, PhD, P. Heckman, PhD

PhD-students:   
B. van Hagen Msc., E. Argirousi Msc., D. Paes Msc., M. Schepers Msc., S. Caldenhove Msc., M. van den Berg Msc.

Co-investigators extern:
A. Blokland, PhD, A. Sambeth, PhD, Prof. J. Ramaekers, PhD (FPN), Prof. H. Schmidt, MD, PhD (CARIM), T. Vanmierlo, PhD, Prof. N. Hellings, PhD (BIOMED, University of Hasselt, Belgium), Prof. O. Bruno, PhD, E. Fedele, PhD (University of Genoa, Italy), D. Puzzo, PhD (Città, Universitaria, Catania, Italy), L. Wennogle, PhD (Intra-Cellular Therapies, New York, USA), O. Arancio, PhD (Columbia University, NY, USA), R. Weffort de Oliveira, PhD (State University of Maringá, Brasil)

Focus of research:   
Cellular signal transduction in affective and cognitive processes in health and disease

The major aim is to unravel the mechanism of action of signaling pathways both in health and disease (e.g. Alzheimer's disease and depression), while at the same time exploring the therapeutic potential of key factors in the affected signaling pathway. The focus in this respect is on the growth factor Brain Derived Neurotropic Factor (BDNF) and the second messengers cAMP and cGMP. Research involves working in a translational context ranging from molecular biology to behavior. We have shown that phosphodiesterase (PDE) inhibitors, which inhibit the degradation of cAMP and/or cGMP by PDEs, improve signal transduction and memory processes in rats independently of cerebrovascular effects. This is of major importance since this indicates that the second messengers can be targets for new drugs to improve memory function directly. Therefore, the biological mechanism of action of specific PDE inhibitors to improve memory is investigated in depth in collaboration with international academic partners (eg. University of Genoa, University of Columbia, State University of Maringá) and pharmaceutical companies. Part of this research is also in close collaboration with Hasselt University and funded by Alzheimer Nederland in which PDEs are being explored at the isoform level as therapeutic targets for the treatment of Alzheimer's disease. Recently, a proof of concept study funded by a grant from ZonMW showed the memory improving potential of the PDE type 4 inhibitor roflumilast in human subjects with age-associated memory impairment. This was done in collaboration with Division 1 of MH&NS and the Faculty of Psychology and Neuroscience (FPN). Next to this, parallel preclinical and clinical studies are ongoing on new therapeutic targets besides PDEs to stimulate signal transduction. Some of these studies were part of the HEaL (Human Enhancement and Learning) project, which is an initiative between schools (MH&NS, CARIM) and faculties (FHML, FPN and SBE) at Maastricht University with the aim to enhance memory function and thus quality of life. This is now followed up within the Center for Integrative Neuroscience (both FHML and FPN) in which the focus is also on miRNA as biomarkers of drug induced changes in neural integrity and cognition. Finally, besides using pharmacological interventions, signaling is manipulated in for instance mouse models of Alzheimer's disease via gene transfer techniques including CRISPR/Cas9 and a microelectroporation approach. The results of these studies will help us to find new therapeutic targets for affective and cognitive disorders.