Integrative Molecular Phenotyping

KI News

Updated: 46 min 24 sec ago

KI researchers awarded grants from the Swedish Childhood Cancer Foundation

Thu, 19/04/2018 - 08:49
Ten researchers at Karolinska Institutet have been awarded grants in the Swedish Childhood Cancer Foundation’s latest call for funding, during which approximately SEK 62 million was allocated. Appropriations include a six-year researcher position and several postdoctoral positions. Karolinska Institutet researchers account for 11 of 26 successful applications. Financing for a six-year senior research position was awarded to Lisa Westerberg of the Department of Microbiology, Tumor and Cell Biology for a project studying the link between the ability of antibodies to move around and an increased risk for childhood cancer. The aim of the study is to better understand how an uncontrolled immune response leads to immunodeficiency diseases and tumours in children. Magdalini Lourda of the Department of Women’s and Children’s Health has been granted funding for a research assistant position relating to immunological and genetic studies of children suffering from the rare condition Langerhans cell histiocytosis. The call also resulted in a grant to five KI researchers for postdoctoral positions. These are Saeed Eshtad, Aida Rodriguez Garcia, Jenny Thorsell Cederberg, Johanna Viiliäinen and Arnika Wagner. Doctoral grants for clinicians were awarded to Susanna Ranta and Emma Tham. Funding for clinical research months – three months per year for three years – was awarded to Bianca Tesi and Emma Tham. In total, approximately SEK 62 million in grants were awarded. From a total of 107 applications, 26 were granted – 17 of which came from women and 9 from men. The Swedish Childhood Cancer Foundation awards grants three times a year.

KI researcher Mandus Frykman appointed national coordinator

Thu, 19/04/2018 - 08:46
The Swedish Government has appointed Mandus Frykman, researcher at Karolinska Institutet, as national coordinator for a well-functioning sick-leave process. This newly established function involves examining how sick leave can be developed from an individual perspective. “I am extremely pleased and proud to be given this assignment. It is incredibly exciting and an opportunity to participate in influencing matters on a large scale,” says Mandus Frykman, a researcher at Karolinska Institutet’s Department of Learning, Informatics, Management and Ethics (LIME). Focus on the individual On 12 April, the Swedish Government appointed Mandus Frykman as national coordinator for the sick-leave process, a newly established function. At the same time, an inquiry was set up into health insurance and both of these initiatives are part of the action programme for health insurance presented by the Swedish Government earlier this year. Mandus Frykman’s research deals with the impact of decisions at board-room level on occupational health and safety. He is a psychologist and economist and is also works in occupational healthcare. As national coordinator, Mandus Frykman will be examining how the sick-leave process works and how it can be developed from an individual perspective. According to the Government, this is a matter of taking the individual’s journey through health insurance as a starting point and placing it at the centre of the process. Several stakeholders in cooperation Because the sick-leave process involves a number of stakeholders – such as employers, healthcare and welfare services, the Swedish Social Insurance Agency and the Swedish Public Employment Service – cooperation is a central concept. “Cooperation between stakeholders in the sick-leave process has proved to be a challenge, and my task is to analyse the preconditions for and promote cooperation between them. I look forward to getting started on the assignment and establishing contacts with the stakeholders and other experts in the field,” says Mandus Frykman. According to Minister for Health and Social Affairs Annika Strandhäll, both Magnus Frykman and Claes Jansson, responsible for the inquiry into health insurance, have a clear mandate to drive development towards a secure and modernised national health insurance. Mandus Frykman is due to deliver an interim report on his assignment on 30 April 2019, with a final report to be published no later than 30 April 2020.

The first occupational therapists and physiotherapists with a Master’s Degree in Dementia Care receive their diploma

Wed, 18/04/2018 - 10:34
Sweden’s first occupational therapists and physiotherapists with a Master’s in Dementia Care will be awarded their diploma today in the presence of HM Queen Silvia at a ceremony at the Royal Palace in Stockholm. The Master's Courses in Dementia Care is part of the efforts being made to improve theoretical and practical competence in the field of dementia care. The Master's Courses in Dementia Care were created four years ago as a joint undertaking by Karolinska Institutet and Silviahemmet. It is the only education of its kind, and has recently been expanded to include occupational therapists and physiotherapists as well as physicians. “It’s extremely gratifying that the first intake of occupational therapists and physiotherapists have now taken their Master’s in Dementia Care and that they will be receiving a diploma as ‘Silvia Occupational Therapists’ and ‘Silvia Physiotherapists’,” says Maria Eriksdotter, head of the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet. “Raising the educational bar for dementia diseases is in keeping with the recently updated national guidelines for dementia care and the government’s aims.” A total of fourteen participants have now completed this round of the Master's Courses in Dementia Care. Among the participants, one of the new degree recipients is the first physician from China to adopt the title of ‘Silvia Doctor’. The care of dementia sufferers has been in focus recently. At the end of last year, the National Board of Health and Welfare issued updated national guidelines for the health and social care of people with dementia, and in mid March this year, the government ringfenced additional funds for raising the quality of dementia care.

Study on fever in children in Africa may change global guidelines

Wed, 18/04/2018 - 06:00
Children in sub-Saharan Africa with uncomplicated fever may be safely managed with conditional, rather than universal, 3-day follow-up with a community health worker, according to a randomised trial by researchers at Karolinska Institutet published in PLOS Medicine. The study suggests that current WHO guidelines for these children could be reconsidered. The WHO’s integrated community case management (iCCM) guidelines recommend that all children presenting with uncomplicated fever and no danger signs return for follow-up with a community health worker on day 3 following the initial consultation on day 1. Such fevers often resolve rapidly, however, and previous studies suggest that expectant home care for uncomplicated fever can be safely recommended. The trial was conducted in Ethiopia and included approximately 4,000 children under age five with uncomplicated fever, who were randomised to receive either conditional follow-up if symptoms remained or the recommended universal 3-day follow up. The results suggest that conditional follow-up is non-inferior to universal follow-up. More efficient use of resources  “Allowing community health workers to advise caregivers to bring children back only in case of continued symptoms might be a more efficient use of resources in these settings,” says first author Karin Källander, adjunct senior lecturer at Karolinska Institutet’s Department of Public Health Sciences. Another study from Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States, published at the same time in PLOS Medicine, shows similar results for children in the Democratic Republic of the Congo (DRC). Additional trials in other sub-Saharan African settings are needed to establish generalisability. However, taken together, the current results provide evidence relevant to formulation of WHO recommendations. The study involving researchers from Karolinska Institutet was made possible by the support of the U.S. President's Malaria Initiative under the United States Agency for International Development's Translating Research into Action (TRAction) Project. This news article is based on a press release from PLOS Medicine. Publication “Universal versus conditional day 3 follow-up for children with non-severe unclassified fever at the community level in Ethiopia: A cluster-randomised non-inferiority trial” Källander K, Alfvén T, Funk T, Abebe A, Hailemariam A, Getachew D, Petzold M, Steinhardt LC, Gutman JR PLOS Medicine, online 17 April 2018, doi: 10.1371/journal.pmed.1002553

New disease model to facilitate development of ALS and MS drugs

Mon, 16/04/2018 - 17:03
Researchers at Karolinska Institutet have developed a new disease model for neurodegenerative diseases such as ALS and MS that can be used to develop new immunotherapies. The model is described in a publication in the scientific journal Nature Immunology. All of the body’s organs contain macrophages, which, as part of the immune system, consume bacteria and other foreign bodies. However, macrophages are also specialised according to the organ in which they operate; in the brain they are known as microglia, and researchers believe that this specialisation is controlled by the cytokine TGF-β, which is a kind of protein.  Involved in interneuronal communication In a healthy brain, microglia are involved in interneuronal communication and the renewal of myelin, the insulating sheaths enveloping axons of nerve cells that enable the transmission of nerve impulses. In diseases like MS and ALS, other immune cells called monocytes can enter the brain via the blood, be transformed into inflammatory cells and cause damage to the neurons and the myelin sheath. The researchers behind the current study had a hypothesis that TGF-β may program monocytes from being inflammatory cells to becoming microglia-like cells. “We already knew that TGF-β is produced in the brain and is important for giving microglia their specialised functions,” says first author Harald Lund, doctoral student at the Department of Clinical Neuroscience, Karolinska Institutet. “So we figured that monocytes should also respond to TGF-β when they enter the brain. We were curious to see what would happen if the monocytes lost the ability to respond to TGF-β.” Developed a disease similar to ALS To test this, the researchers first used a mouse model in which the animal’s own microglia could be removed. This lead to a rapid influx of monocytes into the brain and spinal cord, which gave rise to new microglia-like cells, and the mice displayed no pathological symptoms. But when the researchers then switched off the TGF-β receptors on the new microglia-like cells, they started to consume large parts of the myelin in the spinal cord. The mice quickly developed a deadly neurodegenerative disease, the symptoms of which were similar to those of ALS. The disease model can explain a mechanism that is active in neuroinflammatory and neurodegenerative diseases, and could be used to develop and test new immunotherapies. Today there are no effective treatments. Lack of experimental models “There are many deadly neurodegenerative diseases in humans, but a lack of experimental models for developing new immunotherapies,” says Professor Bob Harris at the Centre for Molecular Medicine, Karolinska University Hospital and the Department of Clinical Neuroscience, Karolinska Institutet. “This new disease model will be a valuable addition to our research programme and we hope that the next study will result in a new, effective therapy.” The study was financed by the Swedish Alzheimer’s Foundation, the Swedish Research Council, the Swedish Childhood Cancer Foundation, the Åke Wiberg Foundation, the Swedish MS Research Foundation, the NIH-NINDS, NIH-NIA, the National Multiple Sclerosis Society, the Amyotrophic Lateral Sclerosis Association, the Swedish Heart and Lung Foundation, the Novo Nordisk Foundation and the Margaretha af Ugglas Foundation. Publication “Fatal demyelinating disease is induced by monocyte-derived macrophages in the absence of TGF-β signaling” Lund H, Pieber M, Parsa R, Grommisch D, Ewing E, Kular L, Han J, Zhu K, Nijssen J, Hedlund E, Needhamsen M, Ruhrmann S, Ortlieb Guerreiro Cacais A, Berglund R, Forteza MJ, Ketelhuth DFJ, Butovsky O, Jagodic M, Zhang X-M, Harris RA Nature Immunology, online 16 April 2018, doi: 10.1038/s41590-018-0091-5

Conference on Global Health gathers researchers and students from the country’s institutes of higher learning

Mon, 16/04/2018 - 13:43
Sustainable development and global health is receiving a great deal of attention at Karolinska Institutet this week. Now, it is time to stop talking and start acting, states Tobias Alfvén, one of the organizers behind The Swedish Global Health Research Conference 2018, being held on April 18-19. What is this conference about? “It is based on the goals of the 2030 Agenda for Sustainable Development that the countries of the world have committed to attaining. It is something that is receiving increasing attention; but currently, there is more talk than action. A great deal of research is being done in Sweden that is relevant to these issues and addresses global health and other areas. But, working independently, each of us at our own country’s institutes of higher learning, is insufficient if we want to make a global difference; that demands collaborative thinking and working. The objective of the conference is to act as a forum for researchers, students and others who want to find a way to contribute.” What kind of conference is it? “We want the conference to be as rewarding as possible, and therefore, feel that there needs to be more than just lectures, even if such can be excellent and inspiring. Thus, more than half of the conference is being given to workshops for smaller groups, where the participants can take the opportunity to discuss specific issues.” Can you give a few examples? “Each participant will be able to reflect on how they, themselves, can contribute to the sustainability goals in terms of their own research or involvement, as well as the challenges that surround the next step, such as getting funding for their research or managing ethical issues. Another group of workshops is based on different research themes, such as pediatric health, safe abortions and antibiotic resistance.” How much interest is there, in the conference? “There will be twice as many participants as we first expected, so interest has exceeded all of our expectations. We are seeing an especially strong response from students throughout Sweden, which is gratifying. I think this reflects a general growing interest for the bigger issues. Many believe that contributions arising solely from their own specializations are insufficient and instead are seeking a broader perspective, which requires getting together and exchanging thoughts and experiences.” What do you hope the participants will take away from the conference? “That they will, even more clearly, realize and know how they can participate in and contribute to the 2030 Agenda. Text: Ola Danielsson

New mutation behind heart failure identified

Thu, 12/04/2018 - 07:00
An international research team involving Karolinska Institutet has identified a new mutation in South Asians that, in combination with a known mutation in the same gene, increases the risk of cardiomyopathy and heart failure. The finding, published in the scientific journal JAMA Cardiology, can lead to improved treatment options for a large number of patients. Four per cent of South Asians, around 100 million individuals, carry a deletion in a gene called MYBPC3. This deletion is known to be associated with an increased risk for cardiomyopathy and heart failure, but to varying degrees. An international team of researchers therefore aimed to find out if there are additional genetic variants that account for this risk variability. By analysing a South Asian population in the US, they found that 10 per cent of the people carrying the MYBPC3 deletion had an additional MYBPC3 mutation. This combination of mutations was linked to clinical findings that increase the risk of heart disease. The results have important implications for personalised healthcare and precision medicine. 10 million people “Our results indicate that around 10 million people worldwide carry the newly found mutation and that it most likely drives the initially described heart failure phenotype observed in patients with a MYBPC3 deletion. This subpopulation of patients are expected to benefit from new, tailored drugs focusing on mutations in the MYBPC3 gene,” says Ralph Knöll, adjunct professor at the Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (ICMC) at Karolinska Institutet's Department of Medicine, Huddinge. The study involved researchers from Karolinska Institutet, AstraZeneca, the University of Cincinnati, and National Heart Research Institute Singapore, among others. The research was funded by the American Heart Association Cardiovascular Genome-Phenome Study, AstraZeneca, Inc., the National Institutes of Health (NIH), the National Research Foundation Singapore, the National Medical Research Council in Singapore, Goh Foundation/Duke-NUS Graduate Medical School, SingHealth Foundation, Biomedical Research Council Singapore, Fondation LeDucq, Deutsche Forschungsgemeinschaft, and the Swedish Heart-Lung Foundation. Publication “Association of Cardiomyopathy With MYBPC3 D389V And MYBPC3Δ25bp Intronic Deletion in South Asian Descendants” Shiv Kumar Viswanathan, Megan J. Puckelwartz, Ashish Mehta, Chrishan J.A. Ramachandra, Aravindakshan Jagadeesan, Regina Fritsche-Danielson, Ratan V. Bhat, Philip Wong, Sangeetha Kandoi, Jennifer A. Schwanekamp, Gina Kuffel, Lorenzo L. Pesce, Michael J. Zilliox, Nalla B. Durai, Rama Shanker Verma, Robert E. Molokie, Domodhar P. Suresh, Philip R. Khoury, Annie Thomas, Thriveni Sanagala, Hak Chiaw Tang, Richard C. Becker, Ralph Knöll, Winston Shim, Elizabeth M. McNally, and Sakthivel Sadayappan JAMA Cardiology, online 11 April 2018, doi: 10.1001/jamacardio.2018.0618

KI researchers awarded the ERC AdG

Fri, 06/04/2018 - 12:05
Two researchers at Karolinska Institutet have been awarded the ERC Advanced Grant (AdG) 2017 from the European Research Council. The two researchers who receive this prestigious award are Henrik Ehrsson and Gunilla Karlsson Hedestam. In total, the ERC allocates funding to 269 European research projects, which is about 12% of all applicants. Henrik Ehrsson Principal investigator: Henrik Ehrsson, Professor of Cognitive Neuroscience, Department of Neuroscience Project: The Unity of the Bodily Self (SELF-UNITY) Application area: Social Sciences and Humanities A characteristic feature of human consciousness is the experience of oneself as a unified single body. Henrik Ehrsson studies the neuronal and behavioral principles that create this experience – how it is uphold under normal conditions and how it can be altered in different ways. In the project currently funded by the ERC, he will try to find out how information from our different senses – such as balance and feelings about the inner state of the body (interoception) – can work together to give us the feeling of a unique bodily self. The identification of the central neurocognitive mechanisms behind this feeling of having one single body would be regarded as true scientific breakthrough. In addition, Henrik Ehrsson hopes that his research will eventually contribute to better treatments for disorders with disturbances in self-unity, such as schizophrenia and stroke with body neglect. More about Henrik Ehrsson’s research Gunilla Karlsson Hedestam Principal investigator: Gunilla Karlsson Hedestam, Professor of Vaccine Research, Department of Microbiology, Tumor and Cell Biology microbiology Project: Defining human adaptive immune gene diversity and its impact on disease (IMMUNDIVERSITY) Application area: Life Sciences Why do people respond differently to infections and vaccination? Why do some people develop immune-associated diseases? We know that adaptive immunity plays a critical role in health management, but little is known about how inherited variations in the genes responsible for antigen recognition influence our bodies' immune responses. To answer these questions, Gunilla Karlsson Hedestam and her research team will explore human adaptive immune gene diversity and its impact on disease, using novel technology and processes. To enable future research in this area, the team will develop robust protocols that allow the analysis of adaptive immune receptor genes from large cohorts of individuals. The project will result in the creation of individualised immune receptor germline gene databases representing thousands of individuals, as well as freely accessible software tools for analysis of immune repertoire data that can be used by other researchers. More about Gunilla Karlsson Hedestam’s research ERC Advanced Grants in numbers Applications 2017 in total: 2167 Granted applications: 269 Of which in Life Sciences: 83 In Social Sciences and Humanities: 60 Granted applications in Sweden: 10 Total women grantees: 47 (17.5%) Source: ERC

Genetic link to IBS identified in women

Fri, 06/04/2018 - 09:15
New research coordinated from Karolinska Institutet links certain DNA variants to increased risk of irritable bowel syndrome (IBS) in women. The findings, published in the scientific journal Gastroenterology, might help explain why IBS is more common in women than in men. Irritable bowel syndrome is the most common gastrointestinal disorder. More than 10 per cent of the population, women more than men, suffer from recurrent symptoms including abdominal pain, gas, diarrhoea and constipation. What causes IBS is largely unknown, which hampers the development of effective treatment for many patients. Genetic predisposition to IBS is recognised, although poorly investigated. Now an international research team led by scientists from Karolinska Institutet in Sweden have identified DNA variants that are associated with increased risk of IBS, but only in women. Region linked to puberty timing “Exploiting the large UK Biobank resource, as well as several patient cohorts from European and US expert centres, we have been able to study genetic predisposition to IBS with increased statistical power, better than ever before,” says corresponding author Mauro D’Amato, visiting professor at Karolinska Institutet’s Department of Medicine in Solna and coordinator of the bellygenes initiative that led to the discovery. The researchers used genotype data from more than 300,000 UK Biobank participants in a genome-wide association study (GWAS). They found DNA variants that associate with increased risk of a doctor’s diagnosis of IBS in women but not in men, specifically from a region on chromosome 9 previously reported to also influence puberty timing in women (age at first menstruation). By following up this result in 2,045 patients from IBS expert centres in Sweden, Belgium, the Netherlands, Italy and the US, the researchers observed further associations with constipation-predominant IBS as well as harder stools, again only in women. Sex-hormones could play a role “Although we cannot point to individual genes at this early stage, we believe these results are exciting, as they converge with existing data on female preponderance and a role of sex-hormones in IBS,” says Mauro D’Amato. In addition to Karolinska Institutet, researchers and clinicians from several other institutions participated in the study, including the Mayo Clinic and University of California Los Angeles in the US, IKMB in Kiel Germany, TARGID in Leuven Belgium, BioDonostia HRI in San Sebastian Spain, the Universities of Bologna in Italy, Groningen and Maastricht in the Netherlands, and others. The research was supported by grants from the Swedish Research Council, the Health Department of the Basque Government, the Spanish Ministry of Economy and Competitiveness (ISCIII), the National Institutes of Health (NIH), and the EU FP7 (BBMRI-LPC), among others. Publication “Female-specific Association Between Variants on Chromosome 9 and Self-reported Diagnosis of Irritable Bowel Syndrome” Bonfiglio F, Zheng T, Garcia-Etxebarria K, Hadizadeh F, Bujanda L, Bresso F, Agreus L, Andreasson A, Dlugosz A, Lindberg G, Schmidt PT, Karling P, Ohlsson B, Simren M, Walter W, Nardone G, Cuomo R, Usai-Satta P, Galeazzi F, Neri M, Portincasa P, Bellini M, Barbara G, Latiano A, Hübenthal M, Thijs V, Netea MG, Jonkers D, Chang L, Mayer EA, Wouters MM, Boeckxstaens G, Camilleri M, Franke A, Zhernakova A, D’Amato M Gastroenterology, online 4 April 2018, doi: 10.1053/j.gastro.2018.03.064

PCSK9 inhibitors have unexpected anti-inflammatory effects

Thu, 05/04/2018 - 09:08
PCSK9 inhibition is a new therapeutic strategy for atherosclerosis which is known to lower LDL cholesterol. Research from Karolinska Institutet, presented at the ESC Congress last year and now published in the Journal of Internal Medicine, shows that PCSK9 inhibitors could ameliorate cardiovascular disease by immune mechanisms that are independent of LDL lowering. Atherosclerosis is a chronic inflammatory process involving cells of the immune system such as T cells and dendritic cells. Lipid-lowering statins are commonly used to treat the condition, and in recent years a new class of atherosclerosis drugs which inhibit the enzyme PCSK9 (proprotein convertase subtilisin kexin 9) has reached the marked. PCSK9 is known to target the LDL receptor, resulting in increased levels of low-density lipoprotein (LDL). Researchers at Karolinska Institutet have examined how immune cells from human atherosclerotic plaques are affected by PCSK9. Using a new experimental system, they found that oxidised LDL, a central player in atherosclerosis, induced PCSK9 and promoted the maturation of dendritic cells. These dendritic cells then mediated the activation of T cells into a pro-inflammatory phenotype. PCSK9 inhibition reversed the effects of oxidised LDL on immune activation. Could be anti-atherosclerotic “This anti-inflammatory effect was unexpected and could potentially be anti-atherosclerotic, suggesting that the benefits of PCSK9 inhibition extend beyond lowering LDL cholesterol,” says lead author Johan Frostegård, Professor at the Institute of Environmental Medicine, Karolinska Institutet. The study was funded by the Swedish Heart-Lung Foundation, the Swedish Research Council, the Stockholm County Council (ALF), the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, Vinnova, AFA Insurance, and Torsten Söderberg Foundation. The authors declare no conflict of interests. Publication “PCSK9 plays a novel immunological role in the oxidized LDL-induced dendritic cell maturation and T-cell activation from human blood and atherosclerotic plaque” Anquan Liu, Johan Frostegård Journal of Internal Medicine, online 4 April 2018, doi: 10.1111/joim.12758

Eva Hellström-Lindberg appointed Wallenberg Clinical Scholar 2018

Wed, 04/04/2018 - 09:32
KI researcher Eva Hellström-Lindberg has been appointed Wallenberg Clinical Scholar 2018, as one out of four researchers. She is granted SEK 15 million to build upon the discovery of a genetic change that is associated with a better disease prognosis of MDS, a form of blood cancer, and develop treatments. Wallenberg Clinical Scholars is part of the SEK 2.5 billion that the Knut and Alice Wallenberg Foundation is investing to boost medical research and the life sciences, Life Science. During the program period, 2015-2025, 25 grants will be awarded to Sweden's foremost clinical researchers. Each researcher is receiving SEK 15 million for a five-year period, with the potential for a five-year extension. Universities with medical faculties are invited to nominate researchers for these research grants and The Royal Swedish Academy of Sciences is responsible for the scientific evaluation. “Sweden has exceptionally good conditions for world-leading clinical research, but it has become increasingly difficult to combine research with the current pressured healthcare system. It is therefore very pleasing that the Knut and Alice Wallenberg Foundation is making such a significant investment and providing some of our most outstanding clinical researchers with such excellent resources. This is a great benefit, both for medical research and for Swedish healthcare,” says Göran K. Hansson, Secretary General of the Academy of Sciences, in a press release. Significantly improved the treatment of blood cancer Eva Hellström-Lindberg, chief physician and professor at the Department of Medicine, Huddinge, Karolinska Institutet, conducts research that has significantly improved the treatment of myelodysplastic syndrome (MDS), a form of blood cancer. Her objectives include being able to predict relapses following a bone marrow transplant, so as to save the lives of even more affected patients. Early treatment of a relapse increases the chance of being able to save the patient’s life. As a Wallenberg Clinical Scholar, Eva Hellström-Lindberg will build upon the discovery of a genetic change that is associated with a better disease prognosis, and develop treatments that can make the disease take a benign course.

Study shows how muscles regulate their oxygen consumption

Tue, 03/04/2018 - 18:00
A new study by researchers from Karolinska Institutet shows that an enzyme called FIH determines how muscles consume oxygen. Without the enzyme, the need for oxygen increases during physical exercise. The finding is of potential significance to elite athletes, who have been found to have higher levels of FIH in their muscles than others. The study is published in the esteemed scientific journal Cell Metabolism. When you exercise, your muscles consume oxygen to produce energy, until the level of oxygen drops below a particular threshold. Subsequently, energy is generated by the process of anaerobic metabolism, which does not require oxygen. However, this leads to the production of lactic acid and eventually exhaustion and cramping. In a new study, researchers demonstrate that the enzyme FIH (Factor Inhibiting HIF) is a key to how this switch-over happens. Precise regulation “We’ve discovered that the muscles regulate oxygen consumption in a very precise way using the oxygen-sensitive enzyme FIH,” says principle investigator Professor Randall Johnson at the Department of Cell and Molecular Biology, Karolinska Institutet. “The enzyme makes sure that the muscles can use a more effective oxygen-based metabolism for as long as possible and then promotes a very quick transition to anaerobic metabolism.” Using mice in which the production of the enzyme was blocked, the researchers found that mice lacking FIH in their muscles require more oxygen than normal when exercising. “We were able to show that without FIH, the muscles use much more oxygen than is otherwise the case,” says Professor Johnson. “This could be of great significance to elite athletes, who, according to an earlier study of ours, have uncommonly high levels of muscular FIH.” Present in all cells and tissues FIH was discovered over ten years ago, but until now no one has understood its exact function. FIH is found in all the body’s cells and tissues, but is 50 to 100 times more abundant in the muscles than in any other part of the body. The findings can now open the way for new forms of metabolism-affecting drugs. “No one’s entertained the idea of developing a drug that affects FIH before, but I think our study will lead to greater examination of that possibility,” says Professor Johnson. “Here you’re able to affect the metabolism itself, perhaps mainly in the muscles, but possibly in other parts of the body too. This can be important in other contexts, such as diabetes and obesity.” The study was conducted in Professor Randall Johnson’s laboratory at Karolinska Institutet, Sweden, and the University of Cambridge, England, and was financed by the Wellcome Trust, the Swedish Research Council, the Swedish Cancer Society and the Swedish Childhood Cancer Foundation. Publication ”The FIH (Factor Inhibiting HIF) asparaginyl hydroxylase regulates oxidative metabolism and accelerates metabolic adaptation to hypoxia” Jingwei Sim, Andrew S. Cowburn, Asis Palazon, Basetti Madhu, Petros A. Tyrakis, David Macías, David M. Bargiela, Sandra Pietsch, Michael Gralla, Colin E. Evans, Thaksaon Kittipassorn, Yu Chinn Joshua Chey, Cristina M. Branco, Helene Rundqvist, Daniel J. Peet, and Randall S. Johnson Cell Metabolism, online 3 April 2018, doi: 10.1016/j.cmet.2018.02.020

Collaboration provides clinical research of the highest quality

Thu, 29/03/2018 - 13:57
A report from the Swedish Research Council shows that the clinical research conducted in collaboration between Karolinska Institutet (KI) and Stockholm County Council (SLL) maintains a very high level of quality. The Swedish Research Council has evaluated clinical research conducted at those county councils that are signatories to what is known as the ALF Agreement, an agreement between the Swedish Government and certain county councils regarding collaboration on educating doctors, conducting clinical research and developing healthcare. The evaluation was based on three different categories; the quality of clinical research, the clinical significance and social benefits of research, and the preconditions for the research. “We will of course be studying the Swedish Research Council’s report in greater detail, but I can confirm that it demonstrates that the scientific quality of clinical research at KI-SLL is very high. The evaluation also points to a high level of quality in terms of the research’s clinical significance, social benefits and the preconditions. This is most gratifying and an acknowledgment of the fantastic job our staff are doing and that our collaboration with SLL is working well,” comments Ole Petter Ottersen, vice-chancellor of Karolinska Institutet. The evaluation was carried out by three external and independent panels appointed by the Swedish Research Council after a nominations process. “One area for improvement is our joint work on implementation, this is to say, our ability to translate our clinical research into practical healthcare applications so that it can really create value for patients. In cooperation with SLL, this will be a priority going forward. We need more research regarding how research results are implemented in healthcare,” says Ole Petter Ottersen. From 2019, a new allocation model will be introduced for ALF funding, the state’s reimbursement for county councils’ undertaking to participate in training doctors and conducting clinical research. This model will mean that 20% of research funding will be allocated based on an evaluation of the quality of clinical research. The Swedish Research Council’s evaluation provides the basis for this allocation. “I would like to emphasis that, in and of itself, our participation in the evaluation has provided us with a great many valuable new insights,” says Ole Petter Ottersen. In parallel with the Swedish Research Council’s evaluation, the Swedish National Board of Health and Welfare has been undertaking a government assignment to evaluate university hospital care. The National Board of Health and Welfare’s report points out that quality is generally good, although there are also areas for improvement here.  

Internationalisation the theme for KI’s Educational Congress

Fri, 23/03/2018 - 12:56
Karolinska Institutet’s biennial Educational Congress took place on 15-16 March. The main focus of this year’s congress was on medical educational research and the internationalisation of education. Leading researchers in both of these fields participated, as well as the Chair of the Swedish Government Inquiry on increased internationalisation of higher education institutions.  “Higher education must be considered equally as important as research and it is not possible to attain high levels of quality in education without internationalisation,” said vice-chancellor Ole Petter Ottersen on opening the congress. Karolinska Institutet’s Educational Congress is a biennial initiative to improve competences among the university’s educators. The main focus of this year’s congress was on medical educational research and internationalisation. “We want to support and encourage teachers in their pedagogical activities and provide opportunities for an exchange of knowledge among educators at KI. We have found ourselves one step ahead in the internationalisation of education, however, we now need to move forward,” said Annika Östman Wernerson, dean of higher education. Internationalisation must permeate everything One of the congress’ opening speakers was Betty Leask, emeritus professor at La Trobe University, Melbourne, Australia and author of the book Internationalizing the Curriculum. She spoke about the importance of widening the concept of internationalisation. It is not simply a matter of mobility, courses in English and the number of international students. Internationalisation is an attitude that must permeate all activities. It includes intercultural competence, globalisation and openness – and should be a component of learning objectives. According to Betty Leask, universities should be educating professional citizens who are flexible, innovative and open to new ideas, making them better professionals in meetings with patients. “The quality of education is raised by focusing on internationalisation at home. And these measures must be purposeful, planned and aimed at all students and teachers, not only those who will be travelling abroad,” said Betty Leask. National strategy for all higher education institutions Agneta Bladh is the Swedish Government’s special investigator and chair of their internationalisation inquiry. Her role includes proposing both a new national strategy for the internationalisation of higher education institutions in Sweden, and how students can gain an international perspective in their education. At the congress, she presented her recently delivered summary report, Internationalisation of Swedish Higher Education and Research – A Strategic Agenda. “Swedish higher education institutions must be able to establish themselves abroad, and overseas stakeholders must have the opportunity to establish themselves in Sweden. International experience should be considered a merit and we need to include ethical perspectives in international collaborations,” said Agneta Bladh. Prize-winner among keynote speakers Another keynote speaker was Brian Hodges, professor at the University of Toronto, Canada and recipient of KI’s 2016 Prize for Research in Medical Education. He spoke about how technological developments are opening the way for new professional roles in healthcare and that technical solutions can free-up more time for patient contact and empathy. He also mentioned the importance of understanding the limits of artificial intelligence and that this perspective should be included in study programmes. Today, pedagogical development is about ensuring that students will be able to execute their future professional roles, but also develop as people and be equipped to participate in a multilingual and international labour market. Several speakers pointed out that the goal of KI’s study programmes is not merely to prepare students for their future professions in medicine and health, but also to be good citizens of an increasingly global society.  The Educational Congress is organised by the Centre for Learning and Knowledge on behalf of KI’s Board of Higher Education, this year in collaboration with the Gunnar Höglund and Anna-Stina Malmborg Foundation. Text: Sabina Bossi and Sabina Giulini

New study elucidates link between PCOS and anxiety

Thu, 22/03/2018 - 19:00
Maternal obesity and androgen excess induce sex-specific anxiety in the offspring, according to a study on mice by researchers at Karolinska Institutet in Sweden published in The FASEB Journal. The findings may help explain why children born to mothers with polycystic ovary syndrome (PCOS) have increased risk of developing anxiety later in life. PCOS affects more than one in ten women of childbearing age and is characterised by high levels of male hormones in the blood, menstrual disorders, insulin resistance and obesity. The syndrome is also associated with a significantly increased risk of mental illness such as anxiety and depression. The reasons behind PCOS have not been clarified, but environmental factors during fetal life, such as maternal obesity or exposure to male hormones (androgens) via the mother's blood, are thought to be important risk factors. “The fact that daughters of women with PCOS are at increased risk of developing the condition and that sons often develop obesity and insulin resistance, indicates that the fetal environment plays a crucial role,” says Professor Elisabet Stener-Victorin at Karolinska Institutet’s Department of Physiology and Pharmacology who led the study. Studied the mice’s behaviour  The researchers investigated 16 groups of female and male mice offspring exposed to maternal diet-induced obesity and male hormone excess and studied how these environmental factors affected the mice’s behaviour as well as gene expression in the brain. After birth, half of the mice were exposed to high-fat–high-sucrose (HFHS) diet-induced obesity to also investigate the effect of diet in the offspring. The study revealed sex-specific, anxiety-like behaviour in the offspring of both normal-weight and obese pregnant mice exposed to the androgen dihydrotestosterone. Independent of the mothers’ other diet components, female offspring exposed to maternal androgens in utero developed an anxiety-like behaviour. A HFHS diet after birth did not significantly affect the female mice’s behaviour. Male offspring, on the other hand, were unaffected by the elevated maternal androgen levels, but displayed anxiety-like behaviour in response to maternal obesity. Affected genes in the brain The environmental factors also affected gene expression in the brain. A number of genes implicated in anxiety were dysregulated in the amygdala and hypothalamus in the brain in a sex-specific manner. “The novelty of our study is the multifactorial approach, which made it possible to show that females are more sensitive to androgen exposure during fetal life while males are more sensitive to diet-induced obesity. These are previously unknown biological mechanisms that can increase our understanding of why both daughters and sons of women with PCOS are at higher risk of developing anxiety in adulthood,” says Maria Manti, doctoral student in Elisabet Stener-Victorin’s research group. The study was funded by the Swedish Research Council, the Strategic Research Programme in Diabetes at Karolinska Institutet, Novo Nordisk Foundation, Jane and Dan Olsson Foundation, and Adlerbert Research Foundation. Publication “Maternal Androgen Excess and Obesity Induce Sexually Dimorphic Anxiety-like Behavior in the Offspring” Maria Manti, Romina Fornes, Xiaojuan Qi, Elin Folmerz, Angelica L. Hirschberg, Thais de Castro Barbosa, Manuel Maliqueo, Anna Benrick, Elisabet Stener-Victorin FASEB Journal, online 22 March 2018

KI researchers receives grants from Swedish Fund for Research Without Animal Experiments

Tue, 20/03/2018 - 10:23
Three Karolinska Institutet researchers have received grants from research foundation the Swedish Fund for Research Without Animal Experiments. This year, the foundation will be dividing SEK 2.3 million between 14 different projects. Ewa Ellis of KI’s Department of Clinical Science, Intervention and Technology (CLINTEC) will receive SEK 200,000 for her project on Large scale production of human liver spheroids. Pekka Kohonen of KI’s Institute of Environmental Medicine has received a follow-up grant of SEK 150,000 for the continuation of his project Deepened mechanistic validation of toxicity pathway functionality in a patented analysis tool for toxicity prediction. Hanna Karlsson of KI’s Institute of Environmental Medicine receives SEK 200,000 for the project New cell models for improved assessment of genotoxicity and cancer risk of nanoparticles. What does this grant mean to you, Hanna Karlsson? “It feels great to receive a grant that is so clearly aimed at the goal of replacing animal experiments. I have great hopes that it will prove possible to develop an improved methodology for health-risk assessment that is based on information from cell studies rather than animal experiments. It is important in allowing us test more nanoparticles more rapidly, thus contributing to a more sustainable development.” What are you researching? “I research the damaging effects of nanoparticles; small particles that are being produced and used on an increasing scale industrially and in various consumer goods. Primarily I study their effects on lung cells and mechanisms that can lead to the development of cancer. One overarching goal is to understand which particles are damaging and why.” What do you use instead of animal experiments? “I use various cellular models and attempt to develop and test new models that better replicate an actual exposure. Among other things, we cultivate several cell types together, in what are known as co-cultures, expose the cells to an air mixture of particles and study the changes when lung cells are exposed to a low dose of nanoparticles for a relatively long period of time. 

UKÄ criticises KI’s admissions to doctoral education

Fri, 16/03/2018 - 10:38
The Swedish Higher Education Authority (UKÄ) has aimed criticism at Karolinska Institutet’s admissions procedure for doctoral students. UKÄ is critical of the procedure in that the eligibility of applicants is not examined at an earlier stage, as well as that applicants may be offered a limited period of 4-6 months employment as R&D trainees. In the opinion of UKÄ, KI’s admission procedure contravenes the procedure for admission established in the Swedish Higher Education Act and Higher Education Ordinance. “We welcome this clarification and will immediately begin working to prepare a plan to amend this procedure in accordance with UKÄ’s decision,” says Marianne Schultzberg, dean of doctoral education. “This is a part our drive to professionalise admissions and further improve the quality of our doctoral education. We must now identify suitable processes to ensure that the admissions process is transparent for applicants and guarantees the quality of our doctoral education and research, while at the same time increasing efficiency,” says Marianne Schultzberg. UKÄ calls for a report on the measures to be taken as a result of this decision no later than 2 May.

"We are currently in an exciting era for psychological research"

Thu, 15/03/2018 - 11:45
Five questions for Professor Emily Holmes of the Department of Clinical Neuroscience at Karolinska Institutet, who led The Lancet Psychiatry Commission on psychological treatments research in tomorrow’s science. How did this post come to you and what were the commission’s conclusions? “Two years ago, a large group of us met in London for a full day of brainstorming and discussion in small groups. Our number included researchers and clinicians in fields such as psychology, experimental psychology, psychiatry and neuroscience.  During that day, there was fantastic energy in the room. We therefore continued to work over the following months, which proved to be an extremely creative period. We have questioned things that we previously took for granted. The ten areas we collectively decided to highlight are actually ten examples of big questions. Among other things, these reflect our desire to see research aimed at helping more people more effectively. One of the questions deals with how pharmacological and psychological treatments work in combination. We also ask the questions: what should we do in order to improve psychological treatments, and to achieve global reach?” Conference discussion The 10 action points for future psychological research will be presented in more detail at a conference in Nobel Forum, Karoliska Institutet campus Solna on 16 March at 9:00-12:00 hrs (registration required). The Commission was led by Emily Holmes, and the coauthors are Ata Ghaderi, Catherine J Harmer, Paul G Ramchandani, Pim Cuijpers, Anthony P Morrison, Jonathan P Roiser, Claudi L H Bockting, Rory C O’Connor, Roz Shafran, Michelle L Moulds and Michelle G Craske. Why was the commission necessary? “We are currently in an exciting era for psychological research. Although we have good evidence-based psychological treatments in areas such as anxiety and depression, we need to do better. Even our best treatments may help only 50 percent of patients and, from a global perspective, there are many people who do not have access to them.” How do you believe that these ten areas/questions will be received? “There is a great deal of exciting research waiting to be undertaken! We believe and hope that the questions will lead to a debate and inspire discussion about the goals of future psychological treatment research. And that these discussions will contribute to new ways of thinking. For example, we would like to engage those already researching so that they begin to question why a given psychological treatment works.” What is your personal favourite among the ten areas/questions? “Number 1 is, what are the underlying mechanisms that make treatments effective? But of course, we need to work together on all of the questions and even more areas we have not been able to cover here in order to ensure success and ongoing development across the entire research field of psychological treatments and mental health.” What are your hopes for future psychological treatment methods? “Karolinska Institutet is one of the first medical universities in the world with a clinical psychology training programme. Everyone who teaches on the programme is an active researcher. This creates a strong connection between scientific research and education. This helps us to enable a new generation of psychologists and clinicians who are interested in learning why therapies work and we believe that this will make them open to new treatment developments.” Text: Maja Lundbäck (in translation from Swedish) Ten action points for future psychological treatment research 1. How do existing treatments work? We know that some psychological treatments are effective. However, this knowledge is insufficient. What is required now are research initiatives that put their finger on exactly what provides the positive effects of individual treatments (and also when they don’t work). What are the key mechanisms behind existing successful methods? Research into these mechanisms may offer us good opportunities to identify better treatments. 2. Where? Research to improve mental health worldwide. Lack of access to psychological treatment is a major problem. In order to promote access to psychological treatment globally, we must continue to develop rapid, flexible initiatives. We also need to continue to assess how effective these initiatives are and adapt them to work in many cultures. 3: With what? The potential for synergistic treatment effects. A greater understanding is required into the clinical effects of psychological treatment in combination with other treatments, such as pharmacology. Attempts to develop and investigate the effects of new combined treatments may contribute to new advances in treatment. 4. At what stage of life? The science of psychology, prevention and early intervention. Poor mental health early in life often leads to social and economic problems. We should therefore prioritise the development of effective, preventative interventions for use early in life. We need to identify risk factors for mental illness, as well as identify an optimal point in time for these preventative interventions, thereby increasing the chances of a child growing up with good mental health. 5. Psychological treatment through new technologies. New technologies have provided us with exciting opportunities for disseminating evidence-based methods and obtaining improved effects from various treatments. The Internet, VR and mobile apps are examples of how technology can be utilised in renewing and making available psychological treatments, as well as helping us to evaluate new treatments. 6. Trials to assess psychological treatments. The results of randomised, controlled studies assessing psychological therapies provide us with important data about how therapies should be used. The Commission has developed several proposals for how further improvements can be made regarding the design and implementation of these types of studies. The purpose of this is to increase the credibility and quality of future studies in order to better guarantee auditing and, over time, increase the quality of treatment. 7. Education – cultivating a vision of interdisciplinary training. Past collaboration between basic researchers and clinicians have led to historical advances in psychological treatments. Such collaborations have become less apparent over recent years. The Commission therefore proposes opportunities for improving interdisciplinary education. Improved links between clinical psychology, psychiatry and basic research skills may provide greater opportunities for new advances in treatments. 8. Who should we treat, for what and how? Mental health is complex and evidence-based treatments must take account of this complexity. Aside from the variation in symptoms from illness to illness, there is also a large degree of comorbidity. When selecting a form of treatment, there is a choice between individual treatment models or more universal methods that work against a variety of mental health difficulties. One future goal will be to investigate whether individual methods improve the effects of the treatment or if universal methods are better. 9. Suicidal tendencies – saving lives. Despite developments in understanding risk factors for suicide attempts, and a certain degree of development in treatments and preventative interventions, many questions remain as to how more lives can be saved. Some areas that the Commission has identified as important for future research includes the use of new technologies, the role of culture, and input from individuals and others with personal experience related to suicide– we need to expand and use many approaches here. 10. Innovation and audit of future psychological treatment research. The task of improving psychological treatments is an exciting one for all researchers and clinicians with an interest in the science “mental life” and all associated disciplines. New ideas must be investigated and we need to consider what people are actually interested in being treated for. New ideas must be audited carefully while still encouraging innovation. We are currently only at the beginning and more than just these ten areas require our attention if we are to advance psychological treatment research. Publication The Lancet Psychiatry Commission on psychological treatments research in tomorrow’s science Emily Holmes, Ata Ghaderi, Catherine J Harmer, Paul G Ramchandani, Pim Cuijpers, Anthony P Morrison, Jonathan P Roiser, Claudi L H Bockting, Rory C O’Connor, Roz Shafran, Michelle L Moulds och Michelle G Craske The Lancet Psychiatry, online 23 February 2018, doi: 10.1016/S2215-0366(17)30513-8

New biomarkers for neuroblastoma

Tue, 13/03/2018 - 11:00
Researchers at Sahlgrenska Academy in Gothenburg and Karolinska Institutet, among others, have identified two new significant biomarkers for the childhood cancer neuroblastoma. The findings are published in the journal Cancer Cell. "These results may have a direct impact on disease prognosis and in the long-term also improve treatment of neuroblastoma", says Per Kogner, Professor of Child Oncology at the Department of Women’s and Children’s Health, Karolinska Institutet, and one of the study authors. The study was led by Professor Chandrasekhar Kanduri, Sahlgrenska Academy.   Read more in a press release from the Sahlgrenska Academy About neuroblastoma from the Swedish Childhood Cancer Foundation  Publication Sense-Antisense lncRNA Pair Encoded by Locus 6p22.3 Determines Neuroblastoma Susceptibility via the USP36-CHD7-SOX9 Regulatory Axis Tanmoy Monda, Prasanna Kumar Juvvuna, Agnete Kirkeby, Sanhita Mitra, Subazini Thankaswamy Kosalai, Larissa Traxler, Falk Hertwig, Sara Wernig-Zorc, Caroline Miranda, Lily Deland, Ruth Volland, Christoph Bartenhagen, Deniz Bartsch, Sashidhar Bandaru, Anne Engesser, Santhilal Subhash, Tommy Martinsson, Helena Carén, Levent M. Akyürek, Leo Kurian, Meena Kanduri, Maite Huarte, Per Kogner, Matthias Fischer, Chandrasekhar Kanduri Cancer Cell, online 12 March 2018, doi: 10.1016/j.ccell.2018.01.020

Aggressive breast cancer can be transformed into a treatable form

Mon, 12/03/2018 - 18:20
Researchers at Lund University and Karolinska Institutet have uncovered a way to treat aggressive breast tumours through manipulation of the connective tissue cells of the tumour. The researchers are now developing a new drug that transforms aggressive breast cancer so that it becomes responsive to standard hormone therapy. The findings are published in Nature Medicine. Approximately 10–15 per cent of breast cancer patients have so-called basal breast cancer that do not respond to treatment with hormone therapy, which means that they are more aggressive and often recur. Recent studies emphasise the importance of the communication of cancer cells with other cell types in the surrounding tissue, such as connective tissue, blood vessels and immune system cells, enabling the tumours to form, spread and resist treatment. In the new study, researchers have revealed a growth factor – PDGF-CC – which transmits information between the tumour cells and the connective tissue cells, mainly in basal breast cancers. “Detailed analyses of around 1,400 breast cancers showed that high levels of PDGF-CC in the tumour cells were associated with a poor prognosis”, explains Kristian Pietras, Professor at Lund University. He led a multidisciplinary and international research team based at the Lund University Cancer Centre at Medicon Village, in collaboration with researchers from Karolinska Institutet, the Olivia Newton-John Cancer Research Institute in Melbourne, Australia, and University Hospital Bonn. “Previously, it was believed that the various subgroups of breast cancer originated from different cell types in the mammary gland. Our research has shown that connective tissue cells can also modify tumour cells directly with regard to their sensitivity to hormones, which has significant implications in the development of more effective treatments”, says Professor Ulf Eriksson at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics, who initiated the study together with Professor Pietras. New biological drug  In experimental models, the researchers tested a new biological drug that they have developed, which blocks the PDGF-CC-mediated communication between the tumour cells and the connective tissue cells. This resulted in the transformation of the basal breast cancers into hormone-sensitive (luminal) breast cancers. As a consequence, the tumours then became highly responsive to conventional hormone therapy. ”We were also able to show the opposite; that a hormone-sensitive breast cancer can be transformed into a more aggressive, difficult-to-treat cancer if it is able to communicate with connective tissue cells through PDGF-CC”, says Hong Li, researcher in Ulf Eriksson’s research group at Karolinska Institutet. The study was funded to a large extent by a donation from Göran and Birgitta Grosskopf, as well as research funding from the European Research Council, the Swedish Cancer Society, the Swedish Research Council, and the National Health and Medical Research Council Australia. Kristian Pietras, Ulf Eriksson and Pernilla Roswall are named inventors on a patent application relating to the findings of this study. Kristian Pietras, Ulf Eriksson and Andrew M Scott are shareholders of Paracrine Therapeutics that develop inhibitory agents to PDGF-CC. This news article is based on a press release from Lund University. Publication Microenvironmental control of breast cancer subtype elicited by paracrine platelet derived growth factor-CC signaling Pernilla Roswall, Matteo Bocci, Michael Bartoschek, Hong Li, Glen Kristiansen, Sara Jansson, Sophie Lehn, Jonas Sjölund, Steven Reid, Christer Larsson, Pontus Eriksson, Charlotte Anderberg, Eliane Cortez, Lao H Saal, Christina Orsmark-Pietras, Eugenia Cordero, B Kristian Haller, Jari Häkkinen, Ingrid JG Burvenich, Elgene Lim, Akira Orimo, Mattias Höglund, Lisa Rydén, Holger Moch, Andrew M Scott, Ulf Eriksson, Kristian Pietras Nature Medicine, online 12 March 2018, doi: 10.1038/nm.4494