U NIVERSITY OF COPENHAGEN FACULTY OF HEALTH AND MEDICAL SCIENCES

BRIDGE- TRANSLATIONAL EXCELLENCE PROGRAMME

PROJECT SYNOPSIS TEMPLATE 1

Project title Exploring the direct and inverse comorbidities in dementia and related diseases using laboratory tests and clinical features

Mentor 1 Søren Brunak, Dr., Prof., Research Director, NNF Center for Protein Research, Faculty of Health and Medical Sciences, UCPH ( [email protected])

Mentor 2 Ruth Frikke-Schmidt, MD, DMSc, PhD, Professor and Deputy Head at Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen and Chief Physician at Department of Clinical Biochemistry, Centre of Diagnostic Investigations, Rigshospitalet ([email protected] )

Framework The Translational Disease Systems Biology group and the group at the Department of Clinical Biochemistry offer an ideal environment for a candidate aiming in developing biomedical evidence oriented skills fundamental for building the next generation of scientists in the clinical domain. Our labs have granted access to an incredible amount of data including the Danish National Patient Registry, the laboratory information system, clinical notes, diagnoses and prescriptions for millions of patients. The lab headed by Prof. Brunak counts more than 40 members consisting of medical doctors, computational biologists and computer scientists. The lab headed by Prof. Frikke-Schmidt includes medical doctors, physicists/mathematicians, medical students and bio-technicians. The Frikke- Schmidt group is grounded within the combined areas of clinical biochemistry, genetics/genomics of cardiovascular disease and dementia, causality of biomarkers, and registry-based epidemiology. By combining the complementary and shared knowledge from the two labs the basis for a truly translational research environment is present.

Project The temporal analysis of comorbidities is a powerful tool to improve our synopsis understanding of complex diseases. There is a lack of scientific consensus regarding comorbidities in patients affected by dementia and related disorders. These

1 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.

association s represent an incredible opportunity to gain insight into the PAGEshared 2 OF and2 non-shared pathways driving these diseases. Because we can refine disease associations with historical and real-time routine biochemical measures and drug- prescription data, we have the opportunity to pinpoint pathways, that may be modifiable. The potential of these robust data is to fill in the unmet need for evidence-based prevention and treatment strategies for common diseases of the aging population. The fellow will be involved in the analysis of lab tests, clinical notes, diagnoses and prescriptions for millions of patients, looking for trends of comorbidities in dementia patients.

Profile of The ideal candidate has experience in the following areas: potential fellow - biology of complex diseases; - bioinformatics; - systems biology/medicine; - experience with big data, lab data and electronic patient records; - experience with data integration and network biology approaches.

UNIVERSITY OF COPENHAGEN FACULTY OF HEALTH AND MEDICAL SCIENCES

BRIDGE- TRANSLATIONAL EXCELLENCE PROGRAMME

MENTOR CV TEMPLATE

Name Søren Brunak

Title Professor , Research Director

Current department(s) Novo Nordisk Foundation Center for Protein Research , University of Copenhagen

Current position(s) 2007 -: Professor of Disease Systems Biology, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen. 2015-: Senior Medical Informatics Officer, Rigshospitalet, Denmark. 1999-: Professor of Bioinformatics, Dept. of Bio and Health Informatics, Technical University of Denmark.

Education/training 2002: Dr.phil. (honoris causa), Natural Science Faculty, Stockholm University. 1991: PhD in Computational Biology, Department of Structural Properties of Materials, Technical University of Denmark. 1987: MSc in Physics, Niels Bohr Institute, University of Copenhagen, Denmark

Scientific career profile Søren Brunak is a leading expert in bioinformatics, systems biology, and medical informatics through invention and introduction of new computational strategies for analysis and integration of biological and clinical data. His current group is named “Translational Disease Systems Biology” and aims at obtaining mechanistic understanding of disease as well as producing new patient stratification, risk prediction and treatment selection principles. The use of the patient trajectory concept is a major theme that exploits information on the patient-past in terms of prior diseases, comorbidities, prescriptions, lab values, genetics, wearable data, socio-economic data among other types of data.

The impact of Brunak’s research is a consequence of his ability to combine scientific disciplines in novel ways, including computer technology (supercomputer hardware, data protection techniques and software including machine learning techniques), biological, biomedical and biotechnological insights. His multi-disciplinary approaches, where concepts from different areas have been combined, have led to advances in the understanding of the function of biological systems, and thereby fundamentally improved the possibilities for control of disease via novel intervention strategies, and enhancement of health in general.

Søren Brunak has been a member of the Royal Swedish Academy of Sciences since 2016, the Royal Danish Academy of Sciences and Letters since 2004 and the European Molecular Biology Organization since 2009. Søren Brunak is serving on many scientific advisory boards and international funding bodies.

Bibliometric Søren Brunak has published more than 300 papers in international peerPAGE 2 reviewedOF 3 scientific summary journals, co-authored four books, three proceedings and edited books. Søren Brunak’s Scopus citations exceed 55,000, H-index is currently 85 based on Scopus. For Google Scholar, the number of citations exceeds 80,000 with an H-index of 96, which includes books and other publications. He is also included in the Clarivate Analytics/Thompson Reuters listings of “Highly Cited Researchers”, which citation-wise belong to the top 1% in their discipline. Søren Brunak was included in within” Biology and Biochemistry”, 2014, 2015, 2016 and 2018.

10 important publications: -A novel familial cardiac arrhythmia syndrome with widespread ST-segment depression . Bundgaard H, Jøns C, Lodder EM, Izarzugaza JMG, Herrera JAR, …, Brunak S, Wilde AAM, Watkins H, Christensen AH. NEJM 379: 1780-1781, 2018 -Sequencing and de novo assembly of 150 genomes from Denmark as a population reference . Maretty L, Jensen JM, Petersen B, Sibbesen JA, Liu S, Villesen P, Skov L, Belling K, Theil Have C, Izarzugaza JMG, …, Kristiansen K*, Brunak S*, Schierup MH*. Nature 548:87-91, 2017 -Chromosome-wise protein interaction patterns and their impact on functional implications of largescale genomic aberrations . Kirk IK, Weinhold N, Belling K, Skakkebæk NE, Jensen TS, Leffers H, Juul A, Brunak S. Cell Systems 4:1-8, 2017 -Network biology concepts in complex disease comorbidities. Hu JX, Thomas CE, Brunak S. Nat Rev Genet. 17:615-29, 2016 -Human gut microbes impact host serum metabolome and insulin sensitivity. Pedersen HK, Gudmundsdottir V, Nielsen HB, …, Brunak S*, Oresic M*, Ehrlich SD*, Pedersen O*. Nature 535:376-81, 2016 -Temporal disease trajectories condensed from population-wide registry data covering 6.2 million patients . Jensen AB, Moseley PL, Oprea TI, Ellesøe SG, Eriksson R, Schmock H, Jensen PB, Jensen LJ, Brunak S. Nat Commun. 5:4022, 2014 -Mining electronic health records: towards better research applications and clinical care. Jensen PB, Jensen LJ, Brunak S. Nature Review Genetics 13:395-405, 2012 -A human phenome-interactome network of protein complexes implicated in genetic disorders . Lage K, Karlberg EO, Størling ZM, Olason PI, Pedersen AG, Rigina O, Tumer Z, Moreau Y, Pociot F, Tommerup N, Brunak S. Nature Biotechnology 25:309-316, 2007 -Improved prediction of signal peptides: SignalP 3.0. Bendtsen JD, Nielsen H, von Heijne G, Brunak S. Journal of Molecular Biology 340:783-795, 2004 -Cleaning up gene databases . Brunak S, Engelbrecht J, Knudsen S. Nature 343:123, 1990 Contributions to Søren Brunak is or has been the primary supervisor of around 60 PhD theses and 40 Master mentoring, theses. Freedom to operate and independence is often the philosophy behind my mentoring. training, Many of my PhDs and Postdocs have obtained university professorships, group leader positions, supervision or significant industrial roles, including (group leaders/professors) Martin Miller/Cambridge CRUK, Kasper Lage/Broad Institute, Nils Weinhold/Sloan-Kettering, Lars Juhl Jensen/UCPH, Simon Rasmussen/UCPH, Jan Gorodkin/UCPH, Anders Gorm Pedersen/DTU, Chris Workman/DTU, Tune Pers/UCPH and (CEO/other senior role in industry) Thomas Skøt Jensen/Intomics, Niels Tolstrup/Qiagen, Kai Wang/Origimed, Lars Kiemer/Novozymes, Anders Fausbøll/Omnium, Thomas Stranzl/ALK, Claus A. Andersen/GSK Vaccines.

Søren Brunak started many early bioinformatics teaching activities, for example the PhD course “Biological Sequence Analysis” at DTU in 1996 that ran for more than 15 years. Søren Brunak is currently responsible for the course “Bioinformatics for human biologists” offered at UCPH Medical School. He has also contributed to several “big data” teaching programs and masterclasses. His textbook with P. Baldi “Bioinformatics – The Machine Learning Approach”, MIT Press (1998/2001 2nd ed.), has received more than 1,500 citations.

UNIVERSITY OF COPENHAGEN FACULTY OF HEALTH AND MEDICAL SCIENCES

5RIDGE- TRANSLATIONAL EXCELLENCE PROGRAMME

MENTOR CV TEMPLATE 1

Name Ruth Frikke -Schmidt

Title Professor, Chief Physician , MD, PhD, DMSc

Current Department of Clinical Medicine, Faculty of Health and Medical Sciences, department(s) University of Copenhagen and Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital. Current position(s) Professor in Clinical Biochemistry with special focus on cardi ovascular disease and dementia. Chief Physician. Education /training 2018 Professor, University of Copenhagen 2013-2018 Clinical Research Associate Professor, University of Copenhagen 2012- Chief Physician, Rigshospitalet 2008-2012 Consultant, Rigshospitalet 2005-2008 Senior scientist/consultant, Rigshospitalet 2005 Certified specialist in Clinical Biochemistry 2002-2005 Postdoctoral training, Rigshospitalet and University of Michigan 2001 PhD, University of Copenhagen 1997-2002 Specialist training, Herlev University Hospital 1995-1997 Internship, Herlev University Hospital 1995-1995 Research assistant, Rigshospitalet 1995 MD, University of Copenhagen Scientific career My group combines genomics, biochemistry, r egistry -based data and historic profile and real-time blood-based biomarkers from routine hospital care. We strive to elucidate causal pathways for drugdiscovery and preventive strategies. We generate risk prediction scores based on large prospective cohorts – a prerequisite for the implementation of precision medicine in clinical practice. We are a multidisciplinary group consisting of medical doctors, physicists/matematicians, and molecular biologists. All are skilled in genomics, statistics, and biochemistry. We have weekly scientific meetings with a broad range of scientists with presentations, journal clubs and scientific discussions.

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

My scientific track re cord is in translational research with focus on PAGEgen omics2 OF 3 and biomarker discovery of common multifactorial age-related diseases, especially cardiovascular disease, dementia, and diabetes and their interrelationship. In 2010, I was granted the Sapere Aude Research Leader grant from the Danish Council for Independent Research|Medical Sciences of 6 million DKK for projects on common age-related diseases. I am active in international scientific societies, focusing on research-based guidelines, task force documents, and consensus statements, ensuring that high-impact new research is translated into the clinic. I collaborate in several NIH and EU funded projects, and have recently become the Danish representative of the European Alzheimer DNA Biobank initiative - a collaboration exploiting genomic data on state-of-the-art European prospective cohorts. This initiative collaborates with all major dementia consortia, and will jointly address the most important efforts worldwide to decipher the missing heritability of Alzheimer’s disease, to characterize genetic factors potentially involved in dementia conversion, and to set-up the first genome-wide association study (GWAS) of vascular dementia.

Bibliometric In total 126 publications (113 original articles, 5 reviews, 7 summary letters/commentaries, and 1 patent); 15 first, 26 second, and 17 last authorships. Web of Science H-index: 41; 11,877 citations (11,610 without self- citations). Contributions to Mentoring philosophy: mentoring, Trust, expectation alignment, close interaction, and informal discussions. training, Supervision of students: supervision Two post docs (one in specialist training in Clinical Biochemistry, one staff specialist in genetic diagnostics), 5 PhD students (3 principal and 2 project supervisor), one MD and one MD student. Ten successfully finalized PhDs (1 principal and 9 project supervisor). Six finalized bachelor/master projects.

Contribution to teaching: Pregraduate: Continuously from 1997 and onwards teaching medical students. From 2009- 2013 teaching MSc students in molecular medicine and human biology in hematology, genetic concepts and cardiovascular pathology. Since 2014 organized the Clinical Biochemistry part of the course in Diagnostics together with professors and clinical research associate professors in Clinical Biochemistry and matching exam on the 6 th semester bachelor for medical students at the University of Copenhagen. Postgraduate: National Board of Health: Course leader at ”Cardiovascular Diseases” in 2005 and 2009, teacher at ”Course in Molecular Biology” in 2014, as well as teacher at ”The Professional Role of a Clinical Biochemist/Laboratory Doctor” in 2015 and 2018 for MDs under specialist training in Clinical Biochemistry. Teaching at three different PhD courses at the University of Copenhagen. Organizer of a European Atherosclerosis Society Advanced course “Epidemiology and

Genetics of Atherosclerosis, and Causality of Risk Factors” at UniversityPAGE 3 ofOF 3 Copenhagen in October 2018.