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Oluf Borbye Pedersen

Oluf Borbye Pedersen

Professor

  • NNF Center for Basic Metabolic Research

  • Human Genomics and Metagenomics in Metabolism

    Blegdamsvej 3B, DK-2200 Copenhagen N, Maersk Tower, Building: 07-8-55

OLUF PEDERSEN

Current position

Oluf Pedersen (OP) is principal investigator and team leader at Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Denmark (DK) (www.metabol.ku.dk) and Professor of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen.

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

Medical Doctor (MD), University of Aarhus, DK (1972); Doctor of Medical Science  (DMSCi), University of Aarhus (1983); Danish Health Board-authorized Specialist of Internal Medicine (1987) and Specialist of Endocrinology (1987); Chief Physician and Research Director at Steno Diabetes Centre and Hagedorn Research Institute, Copenhagen, a leading European and WHO-collaborative diabetes centre (1989 – 2010); Professor of Molecular Diabetology at the Faculty of Health Sciences, University of Copenhagen (Personal Chair) (1995-2000); from 2001-2011 a similar appointment at University of Aarhus; Professor of Molecular Metabolism at University of Copenhagen, 2008-2011); Professor of Metabolic Genetics, University of Copenhagen (from 2010-); Visiting Professorships at Harvard Medical School, Boston (2 yrs), and Peking Union Medical College and Beijing Genomics Institute (1.5 yrs).
2007-: Founder and Director of Lundbeck Foundation Center of Excellence in Medical Genomics – LuCamp (www.lucamp.org). 2010 - : Cofounder of Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen.

Leadership and Academic Supervision

Extensive leadership experiences with multidisciplinary basic, translational and clinic research teams at Steno Diabetes Centre and Hagedorn Research Institute and as director of two university centers of scientific excellence; university supervisor for 57 research fellows who have achieved their doctor of medicine degree (DMSCi; n=10) or their PhD degree (n=47) and for 56 master students.

Research Focus

OP 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 mentioned common disorders, which are in epidemic growth.

Applying a variety of biological samples, technologies and statistical-genetics methods, the researchers focus on discovering genomic variation that predisposes for common cardio-metabolic disorders. They characterize genomic discoveries 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 centers at studies of the role of the gut microbiota primarily in 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. They explore mechanistically potential dysbiosis of gut microbiota in parallel studies of the metabolome and host physiology markers as well as in animal models.

Selected Examples of Research Innovation

Cell biology: OP developed state-of-the-art methods for isolation of human fat cells and accurate measurement of polypeptide hormone receptor binding, signaling and action in human adipocytes. These have become standard within the research field; he conducted original studies demonstrating molecular causes of insulin resistance in human adipose cells and skeletal muscle tissue; he provided the first demonstration that physical contraction stimulates translocation of GLUT4 in skeletal muscle through a mechanism distinct from that of insulin.

Metabolic genetics: 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. Identification and characterization of multiple gene variants associated with distal and intermediary cardio-metabolic phenotypes. In addition, discovery and characterization of several drugable mutations protecting against type 2 diabetes and cardiovascular disorders.

Gut microbiomics: OP delivered as a leading partner in the EU-Metahit initiative (www.metahit.eu) contributions to the first and second metagenome-sequencing-driven gut microbial gene catalogue of 3.3 and 9.8 mio genes, respectively; with quantitative metagenomics he demonstrated that a fourth of the general white population is markedly deficient in gut microbiota diversity and abundance. The people who are low in microbial genes are featured by insulin resistance, dyslipidaemia and proinflammation; he reported the first quantitative metagenomics study of gut microbiota in diabetes and the discovery of a new biological fingerprint, gut enterotypes. Also through recent studies of the human gut microbiome, his team has been possible to tease out drug effects from disease effects on gut bacteria configuration and function. OP and his team reported the first example of gut microbes linked to human insulin resistance. The studies were followed up mechanistically in interventions in rodents. Recent microbiome studies have been done in prediabetes, cardio-vascular disorders, anorexia, multiple sclerosis and schizophrenia. A regulatory impact of various forms of diet and antibiotics on the human intestinal microbiota is elucidated.

Clinical diabetology: OP contributed with new standards for type 2 diabetes treatments on the basis of 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 gained 7, 9 years of life compared with conventionally treated type 2 diabetes patients with no additional health care cost. 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 outcome of the Steno-2 study, the co-morbidity and mortality of diabetes is declining.

Examples of Scientific Reports (from 2012- )

  • The human intestinal microbiome in Health and Disease. Lynch S & Pedersen O. New England Journal of Medicine. 2016 Dec 15; 375:2369-79.
  • Human gut microbes impact host serum metabolome and insulin sensitivity. 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. Nature. 2016 Jul 21; 535(7612):376-81.
  • Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. 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. Nature. 2015 Dec 10; 528(7581):262-6.
  • Richness of human gut microbiome correlates with metabolic markers. 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. Nature. 2013 Aug 29; 500(7464):541-6.
  • A metagenome-wide association study of gut microbiota in type 2 diabetes. Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D, Peng Y, Zhang D, Jie Z, Wu W, Qin Y, Xue W, Li J, Han L, Lu D, Wu P, Dai Y, Sun X, Li Z, Tang A, Zhong S, Li X, Chen W, Xu R, Wang M, Feng Q, Gong M, Yu J, Zhang Y, Zhang M, Hansen T, Sanchez G, Raes J, Falony G, Okuda S, Almeida M, LeChatelier E, Renault P, Pons N, Batto JM, Zhang Z, Chen H, Yang R, Zheng W, Li S, Yang H, Wang J, Ehrlich SD, Nielsen R, Pedersen O, Kristiansen K, Wang J. Nature. 2012 Oct 4; 490(7418):55-60.

Publications and Bibliometrics

OP is author or co-author of > 800 scientific articles with 740 original papers in peer-reviewed journals including NEJM (7); Nature (11); Nature Genetics (37);  Nature Communications (9); Nature Biotechnology (2): Nature Methods (1); Nature Protocols (1);  Nature Microbiology (2); Science (2); PNAS (3); Lancet (4),;PLOS Genetics (12); Am J Hum Gen (6); J Clin Invest (10); PLOS Medicine (3); Diabetes (76); Diabetes Care (18),;Diabetologia (92); JCEM (60) and 105 scientific reviews or textbook chapters.

Web of Knowledge bibliometrics (Thomson Reuters), July 2018; total citations 49,002; h-index: 95. Google Scholar bibliometrics July 2018: total citations 81, 606: h-index: 114. Featured by Thomson Reuters in 2014 as being among the world’s most influential scientific minds (category: molecular biology & genetics).

Other Scientific Activities

Invited lecturer at >500 international or national conferences. Dissemination of research outcome to the public through popular articles, science web castings, newspapers and magazines and national and international TV.

International and National Scientific Network Development: Principal investigator (PI) partnerships in 7 EU-financed research consortia and 17 long-term research initiatives sponsored by the Danish Research Councils or private Danish research foundations; active partner in development of international scientific networks with the focus on human genetics, e. g. deCODE genetics, DIAGRAM, MAGIC, EGG, Beijing Genetics Institute (BGI), Shenzhen, Lund University, Turku University, Pasteur Institute in Lille and Imperial College in London, Oxford University, Michigan University, Berkeley University, BROAD Institute in Boston, more Universities in New Delhi and Chennai, Peking Union Medical College, Chinese-Japanese Friendship Hospital, Beijing RIKEN and Tokyo University and with focus on human gut microbiomics, e.g. INRA/MetaGenopolis  in Paris, DTU in Copenhagen, EMBL in Heidelberg, University of Gothenburg, VIB Bruxelles University, BGI in Shenzhen and ICAN, Paris.

Recognition and Offices of Honour

OP has received recognition with 17 national and international awards including Claude Bernard, Morgagni, Kroc, Mohan, Hagedorn, Mason, Codan, August Krogh, Aarhus University Alumni Award and The Communication Award of the Danish Ministry of Research and a knighthood by Her Majesty, Queen Margrethe II; president and chair of the Danish Diabetes Association (1995-2000) – a NGO with about 80,000 members; services as chairman or member on boards of scientific societies, biomedical councils, grant bodies and scientific journals.

Contact

Oluf Pedersen, Professor, MD, DMSCi, Novo Nordisk Foundation Center for Metabolic Research, Maersk Tower, Blegdamsvej 3B, DK-2200 Copenhagen N. Building 07-8-55. Mob: +45 29382526

oluf@sund.ku.dk
www.lucamp.org
www.metabol.ku.dk

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