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.
International collaboration
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 furthermore have a collaboration with Professor Torben Hansen (expert in genetics, The Novo Nordisk Foundation Centre for Basic Metabolic Research) which has so far resulted in two papers with me as the last author (Ghouse et al, EHJ 2015, Ghouse et al, GIM 2016). I have been externally affiliated with his group for more than one year.
In addition, for the preceding 5 years, I have been part of the AFGEN consortium, headed by Professor Patrick Ellinor. This work has resulted in two papers (Sinner et al, Circulation 2012, and Roselli et al, Nature Genetics 2018).
I am on the editorial board of Canadian Journal of Cardiology (IF 5.8). The editor-in-chief, Stanley Nattel, is an expert in atrial fibrillation.
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.
Personal information
H index 34 (please see Google Scholar for complete list of publications)
ORCID ID: 0000-0001-9477-5322
Invited international presentations (since 2011)
- “The Genetics of Atrial fibrillation; Metabolic Basis of Cardiovascular Risk”, Hospital de la Santa Creu i Sant Pau, Barcelona, 2018.
- “Giants and Gods – the role of titin in AF”, Norwegian Atrial Fibrillation Research Network, Lysebu, Oslo, Norway, September, 2018.
- “Genetics of familial forms of AF”, Nordic Atrial Fibrillation Symposium, Trolleholm, Sweden, April, 2016.
- “Early-Onset Atrial Fibrillation, LQT3 and SCN5A”, Heart Rhythm Scientific Sessions, San Francisco, USA, May, 2016.
- “Genetics and atrial fibrillation”, International Society for Computerized Electrocardiology, Tucson, Arizona, USA, April, 2016.
- “Genetic determinants of atrial fibrillation”, BCS Annual Conference, Manchester, UK, June, 2015.
- “Targeted Sequencing of Novel Candidate Genes for AF” in a Basic Translational Science Forum entitled “Genomics of AF”, Heart Rhythm Scientific Sessions, Boston, USA, May, 2015.
- “News from the Genetics Lab”, ESC Congress, Barcelona, Spain, September, 2014.
- “Pro and Con Session: Molecular Genetic Testing in Cardiomyopathies”, International symposium - Recent Developments in the Prognostic Assessment and Differential Therapy of Cardiomyopathies, Berlin, Germany, 2014.
- “Genes and Mutations in Patients with Lone Atrial Fibrillation: Do They Matter?”, World Congress in Cardiac Electrophysiology and Cardiology (18th), Cardiostim, Nice, France, 2012.
- “Genetic cause of early-onset lone AF“, International Congress on Electrocardiology, Lund, Sweden, 2010.
Prizes (Both as last author)
- 1st price for the most cited paper in European Journal of Human Genetics, 2013, Nature publishing group (currently 203 citations).
Andreasen C, Nielsen JB, Refsgaard L, Holst AG, Christensen AH, Andreasen L, Sajadieh A, Haunsø S, Svendsen JH, Olesen MS. New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. Eur J Hum Genet, 2013 - 3rd price for the most cited paper in European Journal of Human Genetics, 2012, Nature publishing group (currently 127 citations). Refsgaard L, Holst AG, Sadjadieh G, Haunsø S, Nielsen JB, Olesen MS. High prevalence of genetic variants previously associated with LQT syndrome in new exome data. Eur J Hum Genet. 2012
- I have unsolicited received 300,000 Danish kroner (approx. 40,300 euros) from Fondsbørsveksler Henry Hansen og Hustru Karla Hansen, født Westergaards Legat for research in AF.
Education
- 2011: PhD: Early onset lone Atrial Fibrillation: a genetic disease?
Faculty of Health and Medical Sciences, University of Copenhagen, Denmark and Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Denmark.
Jesper Hastrup Svendsen, Professor MD, DMSc.
Stig Haunsø, Professor MD, DMSc. - 2005: Master of Science, Molecular Biology and Sports Physiology
Faculty of Health and Medical Science, University of Copenhagen, Denmark and Roskilde University Center, Denmark.
Thesis: Gene expression of hormones and transcription factors with importance for muscle remodulation and muscle hypertrophy at Copenhagen Muscle Research Centre, Denmark.
Current positions
- 2020 - Professor, Head of Laboratory, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
- 2015 - Associate Professor, Head of Laboratory, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
- 2013 - Head of Laboratory, Laboratory for Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
- 2013 - Assistant Professor, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
- 2008 - Daily Leader of Laboratory, Laboratory for Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Previous positions
- 2007 – 2011: PhD student, Laboratory for Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
- 2006: Research assistant, Laboratory for Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
- 2006: Research assistant, The Royal Veterinary and Agricultural University, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Fellowships
- 2011 – 2013: Postdoctoral fellowship, Laboratory for Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Supervision of graduate students and postdoctoral fellows
- 2008 – 2019 I have been supervisor for 7 PhD and 11 Master Students.
Teaching activities
- 2013 - Associated Professor, Genetics course, School of Medical Sciences, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
- 2004 - 2006: High School teacher, Biology, Health and Sports, Roskilde Handel and Roskilde Technical High School (350 class teaching).
- 2003 – 2004: Instructor, first year students: temperature regulation and second year students: lung- and circulation physiology. Responsible for theory lessons, exercises, and correction of reports. August Krogh Institute, Faculty of Science, University of Copenhagen, Denmark.
Organisation of scientific meetings
- 2017: Copenhagen Meeting on Cardiac Arrhythmia (May 31-june 2) / Denmark.
- 2021: Copenhagen Meeting on Cardiac Arrhythmia / Denmark.
Commissions of trust
- 2020: PhD thesis opponent at the University of Oslo
- 2019: External expert Norwegian Research Agency (72 mio Norsk kr)
- 2019: PhD thesis opponent at the University of Iceland/deCODE, 2019
- 2016-: Reviewer for Circulation
- 2013-: Editorial Board, Canadian Journal of Cardiology
- 2013-: Reviewer for HeartRhythm
- 2014-: Reviewer for European Heart Journal
- 2014-: Reviewer for Circulation, Cardiovascular Genetics
- 2014-: Reviewer for Cardiovascular Research
- 2013: External expert for the French National Research Agency