Short presentation

Oluf Pedersen and his research team contribute to gain novel insights into the complex and multifactorial aetiology of type 2 diabetes, obesity and cardiovascular disorders – scientific efforts that aim for novel approaches to prevent and treat these common disorders which are in epidemic growth. 

Applying a variety of biological samples, technologies and statistical-genetics methods the researchers are focused on discovering genomic variation that predisposes for common cardio-metabolic disorders. The genomic discoveries are further characterized in genetic-physiology studies of disease intermediary traits and in large-scale studies of genetic-epidemiology elucidating the interaction of gene variants with health behavior (unhealthy dietary habits, sedentary lifestyle and other environmental factors).

Another major research effort is centered at studies of the role of the gut microbiota in primarily metabolic health and risk of metabolic disorders. Here the research team is doing quantitative metagenomics to characterize the human gut microbiome at levels of microbial genes, various taxa and derived functional potentials. Suspected human pathogenic microbiota is studied mechanistically in animal models.

For an update on the European research initiative MetaCardis, see:

http://www.metacardis.net/index.php

CV

OLUF PEDERSEN

Current Position

Group Leader at Human Genomics and Metagenomics in Metabolism, Center for Basic Metabolic Research, University of Copenhagen, Denmark (DK) (www.cbmr.ku.dk) and Professor of Human Molecular Metabolism, Faculty of Health and Medical Sciences, University of Copenhagen.

Education, Authorization, Clinical Career, University Faculties and International Academic Training

Oluf Pedersen (OP) graduated Medical Doctor (MD), University of Aarhus, DK (1972). He was honoured Gold Medal Award for highest academic standing at University of Aarhus (1972). In 1983, he defended his Doctor of Medical Science (D.M.Sc.) thesis at University of Aarhus (1983). OP earned his Danish Health Board Specialist of Internal Medicine and Endocrinology authorizations in 1987. During 1989 – 2010, OP was Chief Physician and Research Director at Steno Diabetes Centre and Hagedorn Research Institute, Copenhagen, a leading European WHO-collaborative diabetes centre.

During 1995-2000, OP was Professor of Molecular Diabetology at the Faculty of Health Sciences, University of Copenhagen (Personal Chair) and from 2001-2011 he held a similar appointment at University of Aarhus. Since 2008 OP is Professor of Human Molecular Metabolism at University of Copenhagen, 2008-); Professor of Metabolic Genetics, University of Copenhagen (from 2010-); Visiting scientist at Harvard Medical School, Boston (2 yrs during 1988-89 and 2001-2002, respectively), and Peking Union Medical College and Beijing Genomics Institute (1.5 yrs during 2008 - 2010). 2007- : Founder and Director of Lundbeck Foundation Centre of Excellence in Medical Genomics – LuCamp (www.lucamp.org). 2010 -: OP co-founded the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen. Director of Section for Metabolic Genetics at Centre for Basic Metabolic Research (2010-2016).

Leadership and Academic Supervision

OP has leadership experiences from multidisciplinary clinical and basic research teams at Steno Diabetes Centre and Hagedorn Research Institute, Copenhagen. In addition from being the director of two major centres of science excellence (LuCamp and Novo Nordisk Foundation Center for Basic Metabolic Research, respectively). He is principal investigator in > 25 international and national research consortia; university supervisor and mentor for 58 research fellows, who have gained their doctor of medicine (Dr Med; n=10) or their PhD (n=48) degrees, and for 58 master students.

Publications and Bibliometrics

OP is or co-author of 760 original and peer-reviewed articles listed in PubMed and Web of Science. He has published many of his original papers in high-impact journals including New England Journal of Medicine (7); Nature (12); Nature Genetics (40); Nature Communications (14); Nature Microbiology (3); Nature Biotechnology (2); Nature Methods (1); Nature Protocols (1); Science (1); PNAS (3); Lancet (4); PLOS Genetics (18); Am J Hum Gen (7); J Clin Invest (10); PLOS Medicine (3); Diabetes (77); Diabetes Care (19); Diabetologia (98); and JCEM (61). In addition, OP has published > 100 reviews and book chapters.

Web of Science bibliometrics (Clavariate Analytics) on July 15, 2019; total citations 59,329; h-index: 102. Google Scholar bibliometrics on July 15, 2019: total citations 119,441; h-index 124. Featured by Clarivate Analytics as being among the world’s most influential scientific minds.
(https://hcr.clarivate.com/#freeText%3Doluf%20pedersen).

Selected Papers

Genetics of diabetes

• Albrechtsen A, Grarup N, Li Y, Sparsø T, Tian G, Cao H, Jiang T, Kim SY, Korneliussen T, Li Q, Nie C, Wu R, Skotte L, Morris AP, Ladenvall C, Cauchi S, Stančáková A, Andersen G, Astrup A, Banasik K, Bennett AJ, Bolund L, Charpentier G, Chen Y, Dekker JM, Doney AS, Dorkhan M, Forsen T, Frayling TM, Groves CJ, Gui Y, Hallmans G, Hattersley AT, He K, Hitman GA, Holmkvist J, Huang S, Jiang H, Jin X, Justesen JM, Kristiansen K, Kuusisto J, Lajer M, Lantieri O, Li W, Liang H, Liao Q, Liu X, Ma T, Ma X, Manijak MP, Marre M, Mokrosiński J, Morris AD, Mu B, Nielsen AA, Nijpels G, Nilsson P, Palmer CN, Rayner NW, Renström F, Ribel-Madsen R, Robertson N, Rolandsson O, Rossing P, Schwartz TW; D.E.S.I.R. Study Group, Slagboom PE, Sterner M; DIAGRAM Consortium, Tang M, Tarnow L, Tuomi T, van't Riet E, van Leeuwen N, Varga TV, Vestmar MA, Walker M, Wang B, Wang Y, Wu H, Xi F, Yengo L, Yu C, Zhang X, Zhang J, Zhang Q, Zhang W, Zheng H, Zhou Y, Altshuler D, 't Hart LM, Franks PW, Balkau B, Froguel P, McCarthy MI, Laakso M, Groop L, Christensen C, Brandslund I, Lauritzen T, Witte DR, Linneberg A, Jørgensen T, Hansen T, Wang J, Nielsen R, Pedersen O: Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes. Diabetologia 56: 298, 2013
  
  
• Lohmueller KE, Sparsø T, Li Q, Andersson E, Korneliussen T, Albrechtsen A, Banasik K, Grarup N, Hallgrimsdottir I, Kiil K, Kilpeläinen TO, Krarup NT, Pers TH, Sanchez G, Hu Y, Degiorgio M, Jørgensen T, Sandbæk A, Lauritzen T, Brunak S, Kristiansen K, Li Y, Hansen T, Wang J, Nielsen R, Pedersen O: Whole-exome sequencing of 2,000 Danish individuals and the role of rare coding variants in type 2 diabetes. Am J Hum Genet 93: 1072, 2013
  
  
• Moltke I, Grarup N, Jørgensen ME, Bjerregaard P, Treebak JT, Fumagalli M, Korneliussen TS, Andersen MA, Nielsen TS, Krarup NT, Gjesing AP, Zierath JR, Linneberg A, Wu X, Sun G, Jin X, Al-Aama J, Wang J, Borch-Johnsen K, Pedersen O, Nielsen R, Albrechtsen A, Hansen T:  A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes. Nature. 512: 190, 2014

The human intestinal microbiome and diabetes

• Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, Almeida M, Arumugam M, Batto JM, Kennedy S, Leonard P, Li J, Burgdorf K, Grarup N, Jørgensen T, Brandslund I, Nielsen HB, Juncker AS, Bertalan M, Levenez F, Pons N, Rasmussen S, Sunagawa S, Tap J, Tims S, Zoetendal EG, Brunak S, Clément K, Doré J, Kleerebezem M, Kristiansen K, Renault P, Sicheritz-Ponten T, de Vos WM, Zucker JD, Raes J, Hansen T; MetaHIT consortium, Bork P, Wang J, Ehrlich S, Pedersen O: Richness of human gut microbiome correlates with metabolic markers. Nature 500:541, 2013
  
  
• Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, Prifti E, Vieira-Silva S, Gudmundsdottir V, Krogh Pedersen H, Arumugam M, Kristiansen K, Voigt AY, Vestergaard H, Hercog R, Igor Costea P, Kultima JR, Li J, Jørgensen T, Levenez F, Dore J; MetaHIT consortium, Nielsen HB, Brunak S, Raes J, Hansen T, Wang J, Ehrlich SD, Bork P, Pedersen O: Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528:, 2015
  
  
• Pedersen HK, Gudmundsdottir V, Nielsen HB, Hyotylainen T, Nielsen T, Jensen BA, Forslund K, Hildebrand F, Prifti E, Falony G, Le Chatelier E, Levenez F, Doré J, Mattila I, Plichta DR, Pöhö P, Hellgren LI, Arumugam M, Sunagawa S, Vieira-Silva S, Jørgensen T, Holm JB, Trošt K; MetaHIT Consortium, Kristiansen K, Brix S, Raes J, Wang J, Hansen T, Bork P, Brunak S, Oresic M, Ehrlich SD, Pedersen O: Human gut microbiota impact host serum metabolome and insulin sensitivity. Nature 535:376, 2016

Clinical trial changing outcome of diabetes care

• Gæde P, Vedel P, Larsen N, Jensen GVH, Parving H-H, Pedersen O: Multifacorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348: 383, 2003
  
  
• Gæde P, Lund-Andersen H, Parving H-H, Pedersen O: Effect of a multifactorial intervention on mortality in type 2 diabetes. New Engl J Med 358: 580, 2008
  
  
• Gæde P, Oellgaard J, Carstensen B, Rossing P, Lund-Andersen H, Parving HH, Pedersen O: Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia 59: 2298, 2016
  
  
• Gæde J, Oellgaard J, Ibsen R, Gæde P, Nørtoft E, Parving HH, Kjellberg J, Pedersen O: A cost analysis of intensified vs conventional multifactorial therapy in individuals with type 2 diabetes: an analysis of the Steno-2 study. Diabetologia 62: 147, 2019

Outreach

OP has given > 540 lectures at national and international conferences including > 50 keynote speeches. Frequently, OP is a communicator in international and national media within the topics metabolic health improvements, intestinal microbiome and human genome.

Recognition and Offices of Honour

In 2006, knighted by Queen Margrethe II (Dannebrog). OP is the recipient of international awards including Claude Bernard, Morgagni, Kroc, Lundbæk and Mohan awards; his national awards include  Hagedorn, Grand Mason, Hanstedgaard, Codan, August Krogh, Bagger-Sorensen, Aarhus University’ Alumni Award, Danish Ministry of Science Communication Award and Niels A. Lassen Prize.
OP was president of the Danish Diabetes Association (1995-2000) – a NGO with about 80,000 members and a professional staff of 35; co-founder of the Danish Diabetes Academy (www.danishdiabetesacademy.dk) and co-founder of Danish Society of Molecular Medicine (www.dsmome.dk/english);

OP has served as chair or member on boards of scientific societies, and national and international biomedical councils, research grant bodies and scientific journals.

Selected Examples of Research Innovation

Clinical Diabetology

OP contributed with new international standards for type 2 diabetes treatment based on findings from the Steno-2 landmark study: a randomized trial comparing the effects of an intensive multifactorial intervention with that of conventional treatment on angiopathy in high-risk patients with type 2 diabetes. The study demonstrated that 8 years of intensive intervention with realistic behavior modifications and individualized polypharmacy against all modifiable risk factors for vascular morbidity cuts the risk of diabetic comorbidities in heart, vessels, eyes and kidneys by half. Similarly, a follow-up assessment 13 years after the initiation of the trial showed a 50% reduction in overall mortality. At 21 years follow-up, type 2 diabetes patients who were originally treated intensively for 8 years gained a median of 7, 9 years of life compared with conventionally treated type 2 diabetes patients. The outcome of this first-in class structured multifactorial and whole-patient-care intervention approach has influenced current international guidelines for diabetes treatment. In parallel with implementation of the Steno-2 study experiences in many countries, the co-morbidity and mortality of diabetes is globally declining.

Intestinal Microbiome Research

OP is a leading partner in the EU-Metahit initiative (www.metahit.eu) which delivered the first and second gut microbial gene catalogue of 3.3 and 9.9 mio microbial genes, respectively, from the human intestinal tract.  With quantitative metagenomics he and his team demonstrated in a population sample that about a fourth of adults is markedly deficient in gut microbiota diversity. The same individuals were featured by insulin resistance, overweight, dyslipidaemia and proinflammation. OP et al. reported the first quantitative metagenomics study of gut microbiota in type 2 diabetes, prediabetics and women with gestational diabetes and they discovered a new biological fingerprint, gut enterotypes of the human host. In addition, in recent studies of the human gut microbiome, Pedersen and colleagues have teased out drug effects versus disease effects on gut bacteria composition and function. Recently, they reported the first example of gut microbes linked to human insulin resistance. Mechanistically the investigators extended and validated their findings in in rodents. The Pedersen team has done several interventions targeting the human gut microbiome and blood metabolome including the impact of broad-spectrum antibiotics and of dietary gluten content, respectively. Studies that influence dietary and medical practice.

Metabolic Genetics

OP has led the discovery of common and low frequency gene variants associated with common cardio-metabolic traits through conduction of pioneering large-scale whole-exome sequencing studies with massive genotyping follow-up. The team has physiologically characterized the potentials of multiple gene variants associated with distal and intermediary cardio-metabolic phenotypes. In addition, they have discovered actionable mutations protecting against type 2 diabetes. OP has together with his longtime collaborator Dr. Torben Hansen delivered evidence for development of precision prevention and treatment approaches in Greenlandic Inuit through discoveries of a series of high-impact gene variants markedly changing carbohydrate and lipid metabolism.

Molecular & Cell Biology

OP has developed state-of-the-art methods for isolation of human fat cells and protocols for accurate measurement of polypeptide hormone binding, signaling and action in human adipocytes. These have become standard within the research field. He delivered original studies that demonstrated molecular causes of insulin resistance in human adipose cells and skeletal muscle tissue and first demonstration that physical contraction stimulates translocation of GLUT4 in skeletal muscle through a mechanism distinct from that of insulin.

Contact

Oluf Pedersen, Professor, MD, DMSCi, Novo Nordisk Foundation Center for Basic Metabolic Research, Maersk Tower, Blegdamsvej 3B, DK-2200 Copenhagen N. Building 07-8-55.

Mob: +45 29382526
[email protected]
www.lucamp.org
www.cbmr.ku.dk