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Anders Rosengren
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Anders Rosengren Group

Research group
Active research
Project owner
University of Gothenburg

Short description

Anders Rosengren, MD, Senior Lecturer (Associate professor) in Molecular Medicine.

About Anders Rosengren Group

Anders Rosengren, MD, Senior Lecturer (Associate professor), integrates clinical investigations, bioinformatics and experimental studies and aims to better understand the pathophysiology of type 2 diabetes and to identify more specific treatment targeted at the underlying disease mechanisms.

He is PI for the "Detailed Mapping of Type 2 Diabetes" (DIACT) study, which is a longitudinal patient study that investigates how the major pathophysiological components in type 2 diabetes are interlinked and develop over time. This is combined with global genetic, gene expression and metabolite data to identify biomarkers associated with pathophysiological components.

Network analysis and other bioinformatics approaches are used to integrate genetic and gene expression data from the patients and to identify disease genes. Candidate genes identified from these analyses are studied experimentally to investigate underlying disease mechanisms. Moreover, a method for drug repositioning is used that compares the gene networks that are perturbed in T2D with a large library of gene expression signatures from drugs to identify potential anti-diabetic compounds.

He is also evaluating the role of gut microbiome in disease progression and drug action in type 2 diabetic patients aiming to enable more personalized treatment and prevention of the disease.

International Collaborations

Anders Rosengren has extensive international collaborations, which includes e.g. Sage Bionetworks in Seattle and University of Oxford. Anders Rosengren was appointed a Ragnar Söderberg researcher in Medicine 2013. He has also recently been awarded a 5-year Future Research Leader grant by the Swedish Foundation for Strategic Research.

Video (3:42)
Research that can provide new diabetes medicine

Group Members

Mei Li

Postdoc

Maria Fälemark

Research Nurse

Birgitta Abrahamsson

Study Coordinator

Jessica Hedin

Research Nurse

Annika Axelsson

Researcher

Emily Tubbs

Affiliated Postdoc

Research Summary

Type 2 diabetes (T2D) is an escalating health problem of enormous proportions. The disease poses a heavy burden on health care systems in both developed and developing countries. Current therapy is insufficient, as evident from the devastating complications in kidneys, eyes and the cardiovascular system. Finding more effective treatment is therefore a great priority.

Our research aims to alleviate this problem by combining clinical investigations, bioinformatics and experimental studies. The integration of all these aspects in the research group provides very interesting opportunities for translational research and drug target identification. "Detailed Mapping of Type 2 diabetes" (DIACT) is a longitudinal patient study that constitutes the major platform of the research group. Newly diagnosed patients with T2D are recrutied from ANDIS (All New Diabetics in Scania) into DIACT, and they undergo comprehensive clinical profiling every 6 months. The study will continue for many years.

Clinical Profiling

The clinical profiling captures different aspects of the pathophysiology. We also obtain global genetic, gene expression ant metabolite data to identify biomarkers associated with the pathophysiological components. The longitudinal design facilitates the distinction between causal and reactive changes.

In the next step, we use network analysis and other bioinformatics approaches to integrate genetic and gene expression data from patient samples and human tissues and to identify disease genes. Candidate genes identified from these analyses are studied in-depth experimentally to characterize the underlying cellular disease mechanisms. The strength of this strategy is highlighted by our recent identification of SFRP4 (Mahdi et al., Cell Metabolism 2012) and ADRA2A (Rosengren et al., Science 2010) as novel disease genes for T2D.

Drug Repositioning

An attractive strategy for expanding the therapeutic options is drug repositioning, which implies finding new indications for approved drugs or for the thousands of compounds that have passed toxicology tests but not yet reached clinical use. One potential benefit with repositioning is that the road to clinical implementation can be considerably shorter compared with de novo drug development. We use a method for drug repositioning that is based on comparing the gene networks that are perturbed in T2D with a large library of gene expression signatures from drugs. The aim is to find drugs that can reverse entire networks of perturbed disease genes. Candidate drugs are then investigated experimentally.

Explorative Plase II Studies

Finally, the most interesting drug targets and candidate compounds as identified from the network analyses and the repositioning approach are studied in the patient cohort as explorative plase II studies. This workflow enables us to start with the patient setting, bring the most relevant findings to the laboratory for mechanistic studies and then translate these findings back to the patients. As an example, we are currently conducting a phase II study investigating the effects of the ADRA2A antagonist yohimbine in patients with a T2D risk variant in ADRA2A.

In addition to the biological studies we are investigating psychological/motivational aspects of T2D. We believe that a combination of improved self-management and new pharmacological approaches is needed to more effectively treat T2D and that studying both aspects in the same study can be highly interesting. The DIACT study provides unique opportunities to explore how biological factors, lifestyle and psychological factors interact and affect disease progression and how motivation to lifestyle changes can be improved. The psychological aspects will be studied using internet-based interventions.

Grants and Awards

Grants as Principal Investigator

  • Ragnar Söderberg Foundation - Ragnar Söderberg Researcher in Medicine 2013

  • Swedish Foundation for Strategic Research - Future Research Leader 2013
  • NovoNordisk Foundation - Excellence grant
  • Swedish Research Council
  • European Foundation for the Study of Diabetes (EFSD)
  • ALF Region Skåne
  • Hjelt Foundation
  • Schyberg Foundation
  • Crafoord Foundation
  • Royal Physiographic Society
  • Albert Påhlsson Foundation
  • Jeansson Foundation

Awards

  • Rising Star Award 2013, the European Foundation for the Study of Diabetes

  • Medeon Prize for Innovations in Diabetes Research 2011

  • Scandinavian Society for the Study of Diabetes, Young Investigator Award 2010

Key Publications

Annika S Axelsson, Emily Tubbs, Brig Mecham, Shaji Chacko, Hannah A Nenonen, Yunzhao Tang, Jed W Fahey, Jonathan MJ Derry, Claes B Wollheim, Nils Wierup, Morey W Haymond, Stephen H Friend, Hindrik Mulder, AH Rosengren
Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes
Science Translational Medicine, 9, eaah4477, 2017 http://stm.sciencemag.org/content/9/394/eaah4477

Axelsson AS, Mahdi T, Nenonen HA, Hänzelmann S, Bagge A, Wendt A, Reinbothe TM, Millstein J, Yang X, Zhang B, Gusmao EG, Shu L, Tang Y, Wang J, Andersson SE, Eliasson L, Artner I, Wollheim CB, Derry JM, Mecham B, Spégel P, Mulder H, Gesteira Costa Filho I, Zhang E, Rosengren AH
Sox5 regulates adult beta-cell phenotype and is reduced in type 2 diabetes
Nature Communications, 15652, 2017. https://www.nature.com/articles/ncomms15652

Tang Y, Axelsson A, Spegel P, Andersson LE, Mulder H, Groop L, Renström E, Rosengren AH
Genotype-based treatment of type 2 diabetes with an alpha2A-adrenergic receptor antagonist
Science Translational Medicine Oct 2014.

Mahdi T, Hänzelmann S, Salehi A, Muhammed SJ, Reinbothe TM, Tang Y, Axelsson AS, Zhou Y, Jing X, Almgren P, Krus U, Taneera J, Blom AM, Lyssenko V, Esguerra JLS, Hansson O, Eliasson L, Derry J, Zhang E, Wollheim CB, Groop L, Renström E, Rosengren AH.
Secreted Frizzled-Related Protein 4 Reduces Insulin Secretion and Is Overexpressed in Type 2 Diabetes.
Cell Metabolism 3;16:625-33. 2012.

Rosengren AH, Braun M, Mahdi T, Andersson SA, Travers ME, Shigeto M, Zhang E, Almgren P, Ladenvall C, Axelsson AS, Edlund A, Gram Pedersen M, Jonsson A, Ramracheya R, Tang Y, Walker JN, Barrett A, Johnson PRV, Lyssenko V, McCarthy MI, Groop L, Salehi A, Gloyn AL, Renström E, Rorsman P and Eliasson L.
Reduced insulin exocytosis in human pancreatic beta-cells with gene variants linked to type-2 diabetes.
Diabetes 61(7):1726-33. 2012.

Rosengren AH, Jokubka R, Tojjar D, Granhall C, Hansson O, Li DQ, Nagaraj V, Reinbothe TM, Tuncel J, Eliasson L, Rorsman P, Salehi A, Groop L, Lyssenko V, Luthman H, Renström E.
Overexpression of alpha2A-adrenergic receptors contributes to type 2-diabetes.
Science 327:217. 2010.