U N I V E R S I T Y O F C O P E N H A G E N

F A C U L T Y O F H E A L T H A N D M E D I C A L S C I E N C E S

B R I D G E - T R A N S L A T I O N A L E X C E L L E N C E P R O G R A M M E

P R O J E C T S Y N O P S I S T E M P L A T E 1

Project title Functional translation of cardiovascular genetics

Mentor 1 Lars Allan Larsen, Professor, Department of Cellular and Molecular Medicine (larsal@sund.ku.dk )

Mentor 2 Henning Bundgaard, Professor, The Heart Center, Rigshospitalet (henning.bundgaard@regionh.dk)

Framework The fellow will work in an environment which combines cardiology, genetics,

molecular biology, cell biology and developmental biology. This work may include

clinical diagnosis, genetic analyses, analysis of gene and protein expression,

experiments with cell models and animal models (zebrafish).

The mentors have many years of experience in identification and functional

characterization of genes and mutations associated with cardiovascular disorders

including arrhythmia, cardiomyopathy and congenital heart disease.

The mentors are part of a recently established Clinical Academic Group in

Cardiology, a research network created with the aim of developing personalized

diagnoses and treatments in cardiology.

The mentors have a strong national and international network of collaborators

from leading research institutions.

Project

synopsis

Many inherited cardiovascular disorders are characterized by a high degree of

heterogeneity, variable expressivity and reduced penetrance. These factors make

genetic diagnosis difficult – in some cases impossible - and may often prevent

optimal treatment of the individual patient.

Identification of new disease genes and genetic variants affecting the clinical

phenotype represents an opportunity to gain novel insight into the genetic and

molecular mechanisms which drive the cardiovascular phenotype.

PAGE 2 OF 2 Such insight may be translated into improved diagnosis and potentially novel drug-

targets – for improvement of future treatment of the patients.

Research projects will focus on functional characterization of genes and mutations

identified in patients suffering from cardiovascular disorders, with the aim of

gaining novel mechanistic insight into cardiovascular pathophysiology. In this way

the present project will bridge clinical and basic research.

To this end, analysis of tissue samples will be combined with experiments in cell

models and animal models.

Profile of

potential

fellow

A background within Molecular Biomedicine, Human Biology, Medicine or similar.

Hands on experience with cell models or animal models.

Proven excellence in research.

U N I V E R S I T Y O F C O P E N H A G E N

F A C U L T Y O F H E A L T H A N D M E D I C A L S C I E N C E S

B R I D G E - T R A N S L A T I O N A L E X C E L L E N C E P R O G R A M M E

M E N T O R C V T E M P L A T E 1

Name Lars Allan Larsen

Title MSC, Phd

Current

department(s)

Department of Cellular and Molecular Medicine

Current position(s) Professor

Education/training 2000: Ph.D, University of Copenhagen. (Molecular genetics). 1993: M.Sc.,

Technical University of Denmark, DTU. (Mol. biology and biochemistry).

Scientific career

profile

Research experience: Research group leader since 2004. Areas of expertise:

medical genetics, genomics, heart development, congenital heart disease.

Joint publications and/or active collaborations with researchers from more

than 15 countries, including CE Seidman, J Seidman, C Burns (Harvard Medical

School, Boston, US), RH Anderson, D Henderson (Newcastle University, UK), V

Christoffels, A Postma, BJM Mulder (AMC Amsterdam, NL), KL McBride

(Nationwide Childrens Hospital, Colombus, US), P Bouvagnet (Hospices Civils

de Lyon, FR), CA Loffredo (Georgetown University, Washington, US), P

Andersen (Johns Hopkins University School of Medicine, US), R Hinton

(Cincinnati Children’s Hospital Medical Center, US), K Devriendt (CU Leuven,

BE), MP Hitz (Welcome Trust Sanger Center, UK), HH Ropers (Max Planck

Institute of Molecular Genetics, GE), K Hayashi (Kyushu University, JP), R

Mathies (University of California, Berkeley, US), J Schouten (MRC-Holland, NL),

M Wenz, M Johnson (Applied Biosystems, Foster City, US), S Baig, M Farooq

(NIBGE. Faisalabad, PK).

Participation in research centers and networks:

1 Do not exceed two pages.

The CV’s and project synopsis of each mentor team will be posted on the programme webpage in advance of the

admissions process to the programme

PAGE 2 OF 2 2017- : Co-PI and steering group member, "Precision Diagnostics in

Cardiology" (Clinical Academic Group, under the direction of Copenhagen

Health Science Partners). 2014 - 17: Co-PI and Steering group member, "Global

Genes - Local Concerns" (UCPH Excellence Programme for Interdisciplinary

Research). 2010 - 13: Partner, Nordic Cilia and Centrosome Network

(established by NordForsk). 2004 - 09: Partner, "Special Non-Invasive Advances

in Fetal and Neonatal Evaluation, SAFE" (EU Framework 6 programme). 2001-

11: Wilhelm Johannsen Centre for Functional Genome Research (centre of

excellence established by the Danish National Research Foundation).

Bibliometric

summary

Author or co-author of 85 peer-reviewed articles (First author: 16,

corresponding author: 20). Scopus H-index 28. ORCID id: 0000-0002-7536-

1172.

Selected publications: (1) Ellesøe SG et al. (2018) Eur Heart J 39:1015-1022. (2)

Koefoed K et al. (2018) Sci Rep 8:9542. (3) Mönnich M et al. (2018) Cell reports

22:2584-2592. (4) Schmid FM et al. (2018) J Cell Biol. 217:151-161. (5) Clement

CA et al. (2013) Cell Reports 3:1806-14. (6) Lage K et al. (2012) Proc Natl Acad

Sci U S A 109:14035-40. (7) Thienpont B et al. Am J Hum Genet 86:1-11. (8)

Lage K et al. (2010) Mol Syst Biol 6:381. (9) Erdogan F et al. (2008) J Med Genet

45:704-709. (10) Larsen LA et al. (2007) Nature Protocols 2: 1458-1466.

Contributions to

mentoring,

training,

supervision

Mentering filosophy: mentoring in a university setting is development of

independent scientists who dares to follow their own ideas.

I have supervised 3 postdocs, 12 PhD students and 20 MS students. I have had

full teaching (550 UAT/year) of medical, molecular biomedicine and

odontology students for +15 years.

U N I V E R S I T Y O F C O P E N H A G E N

F A C U L T Y O F H E A L T H A N D M E D I C A L S C I E N C E S

B R I D G E - T R A N S L A T I O N A L E X C E L L E N C E P R O G R A M M E

M E N T O R C V T E M P L A T E 1

Name Henning Bundgaard

Title Ph.D., Dr.Med.

Current

department(s)

Heart Center, Rigshospitalet

Department of Clinical Medicine, University of Copenhagen

Current position(s) Professor, consultant in cardiology

Education/training 2005: Dr.Med. Faculty of Medicine, University of Copenhagen

2002-2004: Fellowship in cardiology / research in Sydney, Australia

1997: Ph.D. Faculty of Medicine, University of Copenhagen 1988: MD, Faculty of Medicine, University of Aarhus

Scientific career

profile

Research experience: Consultant in cardiology since 2007 and Professor since

2015. Head of The Capital Regions Unit for Inherited Cardiac-vascular Diseases

since 2007. Head of the Clinical Academic Group; Precision diagnostics in

cardiology, 2017. Areas of expertise: Cardiology, inherited cardiac disease. Ph.D.

and doctoral thesis in Na,K-ATPase research in animal and human models using a

wide range of technologies including patch-clamping. This formed the basis for my

interest in cellular mechanisms and paved my way into cardio-genetics.

Research group and scientific environment: The Clinical Academic Group I am

heading has the purpose to develop “precision diagnostics in cardiology” using

omics combined with deep phenotyping. This represents a large research

consortium with 5 cardiac departments and 6 departments at University of

Copenhagen. The concept is to bridge clinical research and basic research

competencies.

Joint publications and/or active collaborations; Researchers from Sidney, Boston,

Prague, Oslo, Lund, Reykjavik, Oxford, Amsterdam and London. All collaborations

related to genetics/cardiology or Na,K-pump regulations.

PI / Co-PI of former and present large Danish nationwide clinical studies.

Bibliometric

summary

Author or co-author of more than 170 articles (First author: 23, corresponding

author: 26). Scopus H-index 28. ORCID id: 0000-0002-0563-7049.

Selected publications:

1. Broendberg AK, Nielsen JC, Bjerre J et al. Nationwide experience of catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations. Heart. 2017;103(12):901-909

2. Nouhravesh N, Ahlberg G, Ghouse J et al. Analyses of more than 60,000 exomes questions the role of numerous genes previously associated with dilated cardiomyopathy. Mol Genet Genomic Med. 2016 ;4(6):617-623

3. Bundgaard H, Axelsson A, Hartvig Thomsen J et al. The first-in-man randomized trial of a beta3 adrenoceptor agonist in chronic heart failure: the BEAT-HF trial. Eur J Heart Fail. 2017;19(4):566-575

4. Veselka J, Jensen MK, Liebregts M et al. Long-term clinical outcome after alcohol septal ablation for obstructive hypertrophic cardiomyopathy: results from the Euro-ASA registry. Eur Heart J. 2016;37(19):1517-23

5. Behrens I, Basit S, Lykke JA, et al. Association Between Hypertensive Disorders of Pregnancy and Later Risk of Cardiomyopathy. JAMA. 2016 8;315(10):1026-33

6. Axelsson A, Iversen K, Vejlstrup N et al. Efficacy and safety of the angiotensin II receptor blocker losartan for hypertrophic cardiomyopathy: the INHERIT randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2015;3(2):123-31

7. Fanoe S, Kristensen D, Fink-Jensen A et al. Risk of arrhythmia induced by psychotropic medications: a proposal for clinical management. Eur Heart J. 2014 1;35(20):1306-15

8. Thorsen K, Dam VS, Kjaer-Sorensen K et al. Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome. Nature Communication. 2017.

9. Iversen K, Ihlemann N, Gill SU et al. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med. 2018 Aug 28. doi: 10.1056/NEJMoa1808312. [Epub ahead of print] PubMed PMID: 30152252.

10. Bundgaard H et al. A Novel Familial Cardiac Syndrome. NEJM, in press.

Contributions to

mentoring,

training,

supervision

My philosophy is to mentor the young researcher to become independent by

involving him/her in all research aspects; propose on novel ideas, develop study

designs, write funding applications, participate in and head meetings, write

summaries, establish contacts to other groups, guide younger colleagues –

everything with focus on trust and responsibility. I always make myself available on

very short notice to discuss, support and make decisions if needed.

Past supervisor for 8 Ph.D. projects. Current supervisor for 6 Ph.D. students and 6

medical students. All my former Ph.D. students have obtained or are close to

obtain the career path they were originally aiming for. Two of these in the private

sector.

I am/have been teacher of pre- and post-graduates in medicine and other health professions for the past 15 years.