Morten Steen Salling Olesen
Molecular Cardiology and Membrane Proteins
2200 København N.
Translational human genetic research involving genetically modified whole animal models
The overall objective of my research is to provide and disseminate new knowledge regarding the pathophysiological mechanisms underlying genetic causes of cardiac disease by genetic sequencing of patients with atrial fibrillation (AF), other arrhythmia diseases or cardiomyopathies.
As an example of our translational research in AF, I would like to mention our nationwide AF sequencing project. In this project, we have taken advantage of the Danish national registers to identify all families affected by AF at a nationwide scale. We have sequenced all protein coding genes in these families and showed that loss of function variants in the TTN gene strongly predispose for AF.
We published the novel finding that these variants had large effect size and this gave us a unique opportunity to study the effect of these variants in CRISPR/Cas9 modified zebrafish. These studies indicated that increased fibrosis and sarcomere defect as an important pathophysiological pathway for AF.
This project was supported with DKK 10 million by the Hallas-Møller grant, Novo Nordisk foundation (2018). The first results were published in Nature Communications in 2018 (Alhberg et al. 2018) and in PNAS in 2019 (Collins et al. 2019). These translational studies involving whole animals have indeed expanded our understanding of AF and highlighted the importance of structural genes, as most of the previous studies had focused on genes involved in electrical function.
The majority of our current project is done in close collaboration with Prof. Didier Stainier, from the Max Planck Institute for Heart and Lung research. Prof. Stainier is a world-leading researcher in heart and vascular development and function in zebrafish. During the last decade, he has done extensive work on cardiac regeneration in zebrafish. I have two ongoing projects with his lab. One relating to the function of TGF-β (an important gene related to fibrosis formation) in vascular development and a second project on the role of PITX2 in heart failure (Accepted for publication in PNAS).
I like to teach and communicate knowledge. I believe that students become more competent when guided, supported and challenged at the same time.
I teach at the Course Medical Cell and Tissue Biology, (2 semester of medical school, University of Copenhagen). It is very interesting to teach this course as it is possible to inspire and give influence the way the students are studying.
In the future I would like to teach in genetic data analyses where there is a stronger focus on understanding and learning about research methods. My competence for designing studies of human genome using next generation sequencing and GWAS would be in focus and well used in such a course.
I have a strong and longstanding interest in exercise physiology. I myself have 15 years as a football player at elite level. My education in exercise physiology and my deep and long-lasting interest in heart diseases is a very fruitful combination for developing new courses where praxis and theory could be combined. I know how to combine these two perspectives and I could contribute to closing of the gap between the hospital system that is mainly focused on people that have become ill and the results of research in exercise physiology, where sports performance traditionally have been in focus.