KI News

A new study from Karolinska Institutet published in The Journal of Epidemiology and Community Health shows that people of a higher socioeconomic position are more commonly diagnosed with glioma, the most common form of adult brain tumour. The results are particularly salient for men. The paper is based on a large population study including 4.3 million people born in Sweden between 1911 and 1961 who studied during the period from 1993 to 2010. The results show a correlation between socioeconomic position and the likelihood of being diagnosed with glioma that although found in both sexes was particularly strong for men. “One reason could be that people with a higher socioeconomic status tend more to seek treatment and are better at speaking for themselves,” says study leader Professor Maria Feychting at the Institute of Environmental Medicine. “Surgery is needed to obtain the biopsy to establish exactly what kind of tumour a patient has. The patient’s state of health generally affects the ability to operate, which can also be related to socioeconomic status.” Less clear resulats Professor Feychting does not, however, think that this is the whole story, since the strength of the correlation varied according to tumour type. The results were less clear for the more benign, slow-growth meningioma and acoustic neurinoma tumours, for which the risk levels were higher, respectively, for men and women in the more highly skilled social groups. “More research is needed to ascertain the causes,” says Professor Feychting. Higher risk Higher education (at least three years at university), higher income and belonging to a higher professional category (socioeconomic status) are all factors that can be associated with the likelihood of receiving a glioma diagnosis.  The study also found evidence of a higher risk for married or cohabiting men. “Manifest symptoms of a brain tumour like glioma can include a personality change,” says Professor Feychting. “If you’re married or living with someone, you have someone around who’ll notice this and make sure you see a doctor.” What do you hope your study will help bring about? “It would be good if it led to a deeper analysis of the care pathway from primary care to neurosurgery, and studies of whether there are differences between men and women, and in different age groups. We also have to study if these associations change with time.” The study was funded by the Swedish Research Council and the Swedish Council for Health, Working Life and Welfare Publication Socioeconomic position and the risk of brain tumour: a Swedish national population-based cohort study Amal R. Khanolkar, Rickard Ljung, Mats Talbäck, Hannah L. Brooke, Sofia Carlsson, Tiit Mathiesen and Maria Feychting  Journal of Epidemiology and Community Health, online 20 juni 2016, doi:10.1136/jech-2015-207002.

During his postdoc period at Harvard University, Ninib Baryawno has learnt to think big, and when he returns to KI next year, he’ll be bringing with him a broader view of research. It might sound mad for someone to switch to another research field when about to do their postdoc period overseas. For Ninib Baryawno, however, it was a deliberate choice. As a doctoral student, he studied medulloblastoma, a form of cancer that creates brain tumours in children and that scientists now believe to be a stem cell disease. Ninib knew even then that he wanted to learn more about stem cells, and so chose to do his postdoc period doing haematological stem cell research at Harvard University in Boston. “I switched to a research field based on completely different kinds of animal model and a different way of conducting research to what I had been used to. The research field has taken great strides forward in a short space of time, which means that the bar for what’s considered high-impact research is set very high. This has made me stronger as a researcher.”  Being a researcher means sometimes having to take brave decisions However, it took a long time for Ninib Baryawno to learn about the field and the new complicated methods. The postdoc period, which he thought would last two or three years, is now into its fifth. The Swedish system, he says, in which grants for junior researchers can only be applied for over a limited number of years after graduation, is not suited to longer postdoc period. This has influenced his plans to return to Sweden. “But it was still right to switch disciplines, because it has been a cornerstone of my research. In combining my background in cancer research with stem cells, I’ve discovered my own niche. Being a researcher means sometimes having to take brave decisions, such as switching fields, which can have long-term synergy effects.” Professor David Scadden, in whose Harvard group he is doing his postdoc research, is keen to obtain a good mix of expertise in his research environment. Ninib Baryawno says that the work here has made him less timid about trying new things and taking on whatever might lie outside his own expertise. He is convinced that it is when you combine people with different backgrounds and competencies that you can make interesting discoveries. “Boston’s something of a paradise for researchers. People are willing to cooperate and share their expertise. One of the most important things that I can take back with me to Sweden is the network that I’ve established here in Boston, and that I can keep working with once I’m back at KI,” he says. Important that the foundation had demonstrated faith in me and my ideas His plan has always been to return to Sweden, and to KI in particular, as he is keen to give something back to the university after having taken his undergraduate and postgraduate degrees here. KI’s renown for its strong research environment plays a part in this, but also the fact that he feels that KI is a university that invests in junior researchers. He recently received a much-coveted research associateship through the Swedish Childhood Cancer Foundation, which also gave him a large project grant. “It changed my life,” he says. “Suddenly I went from that awful uncertainty to being able to breathe out and plan my future. It was also important that the foundation had demonstrated faith in me and my ideas.” He will return to his medulloblastoma research and will be working close to John Inge Johnsen, his former doctoral supervisor. At the same time, he will also be doing research in Boston on bone metastases related to breast and prostate cancer. In both cases it is about studying the mechanisms that determine why some tumours develop resistance to therapy and finding new ways of preventing such drug resistance. To these ends he will be using single-cell RNA analysis on fresh patient material, which makes it possible to study gene expression in individual tissue cells to see what characterises the cells that become resistant. Scientists can get so focused on our own expertise that we forget the big question “I hope to take the step from showing that there are differences between the cells in a tumour to showing that the differences have biological significance for patients,” he says.   One reason why he applied to the US to do his postdoc research was that he wanted to surround himself with a different approach to research; having the courage to ask the difficult questions and to say that as a researcher you want to make a difference in your scientific field. “Cancer researchers should take that step and say that we want to find cures for most cancers and alleviate suffering. I find myself getting irritated at times by how we scientists can get so focused on our own expertise that we forget the big question: what do we have to do to solve this puzzle?” Text: Karin Söderlund Leifler Translation: Neil Betteridge Photo: Lee Hopkins Name: Ninib Baryawno, 34. Financing: Has received financing for a research associateship and project grants in the Childhood Cancer Foundation’s major call for applications this spring. Career in brief: MSc in biomedicine from KI, 2005; PhD from KI, 2010; junior postdoc, 2010–2011 at KI and then in David Scadden’s group at the Department of Stem Cell and Regenerative Biology at Harvard University and Massachusetts General Hospital in Boston, 2011.

The Big Bang Theory isn’t any old sitcom – it’s a show that takes its science deadly seriously and stimulates public interest in science. So says the Young Academy of Sweden, which recently awarded the US TV series the newly created Torsten Wiesel Midnight Sun Award.  The Big Bang Theory is about a group of friends, many of whom are researchers at Caltech in California. One of the characters is played by Mayim Bialik, who alongside her acting career is also a doctor of neuroscience. “What’s so great about The Big Bang Theory is that it takes its science deadly seriously – they run very careful fact checks,” says Christian Broberger, docent of neuroscience at Karolinska Institutet and one of the judges on the Young Academy of Sweden’s awards committee. “They’re really quick at incorporating new discoveries and good at keeping up with the latest research. We believe that the series, which is terrifically popular, has raised science onto the agenda in a light-hearted way for new audiences.” The TV series is also the first recipient of The Torsten Wiesel Midnight Sun Award, which was established to commemorate the 90th birthday of Nobel laureate and neurophysiologist Torsten Wiesel in 2014 in recognition of people or organisations that have made extraordinary efforts to explain or spotlight science. Torsten Wiesel is also the scientific patron of the Young Academy of Sweden, and attended the prize-giving ceremony in May in order to present a work of art to the series’ scientific fact-checker, Professor David Salzberg, particle physicist at the University of California in Los Angeles. Salzberg is also responsible for the now cult-status whiteboard that appears in the series bearing all manner of – always correct – formulae. “Physicists like to send their latest discoveries to Salzberg so they can be written up on the board,” says Dr Broberger. “It’s become a prestige thing to appear there. When Stephen Hawking went to launch one of his latest great theories, part of the pitch was to be included on The Big Bang Theory.” Text: Sofia Stridsman Photo: Warner Bros   Footnote: The five-year old Young Academy of Sweden is a multidisciplinary forum established by the Royal Swedish Academy of Sciences.

A crash course on Karolinska Institutet’s innovation system and insight into how the Grants Office works with external financing and resource mobilisation were on the agenda when Sida’s chief coordinators for projects in Bolivia, Cambodia and countries in Africa came to KI on a study visit on 17 June. It is not always so easy to make national research funds stretch. This is not only a Swedish problem but one that very much affects universities in African countries like Tanzania, Uganda, Rwanda and Ethiopia. If these universities are to quickly build their research capacity, they often need an injection of international funds. On 17 June, KI hosted a half-day programme for chief coordinators of a number of Sida’s programme countries to demonstrate how KI applies for grants from the USA’s NIH and manages the funds it receives. “We’re delighted and proud to be able to present KI and discuss our options for closer collaboration,” says Professor Anders Gustafsson, acting dean of research and the host[NB1]  of the event. Björn Kull, head of the KI Grants Office, spoke about the help it gives to researchers with applications and project administration. Janet Jeppsson, coordinator at the Grants Office explains the reason for the model’s success: “The Grants Office here at KI has been extremely successful when it comes to supporting researchers, not just in the application phase but also in the all-important aspect of following the rules to be seen as a reliable partner,” she says. Sida’s programme countries had also requested information on the innovation process. Former vice-chancellor, Professor Hans Wigzell, showed the visitors how the innovation system works and talked about the holding company model, which makes it possible for KI’s scientists to commercialise their ideas. Joyce Masalu from Muhimbili University of Health and Allied Sciences in Tanzania was one of the delegates: “Innovations don’t happen by chance,” she says. “It takes training for individuals to become innovative, that and access to the proper tools.” Ingeborg van der Ploeg, director of doctoral education and coordinator for one of KI’s current Tanzania programmes: “The better these countries get at attracting and managing research funding, the more attractive they become to us as partners,” she says.   Text: Maja Lundbäck Photo: Stefan Zimmerman

Benedict Chambers and Berit Carow left the world of elite sports to concentrate on their careers as immunologists at Karolinska Institutet. They are now returning to the limelight to help contestants in this summer’s Olympic Games in Rio avoid infection. Berit Carow and Benedict Chambers cut healthy, energetic figures, as one would expect of two former sporting elites. And even though they’re both still active in their respective sports, they dedicate most of their time to research. Benedict Chambers is a docent at the Centre for Infection Medicine at the Department of Medicine, Huddinge, and Berit Carow is a postdoc researcher at the Department of Microbiology, Tumour and Cell Biology (MTC). Together, they have combined their interests and made four short films designed to help Olympic hopefuls avoid the greatest threat to a medal – missing the games due to illness. As part of its training drive, the International Olympic Committee (IOC) has opened an “Athlete Learning Gateway”, a collection of online courses and instruction films on health, nutrition and performance tips. The idea for the project came to Dr Chambers when he saw that there was no information about infections and how to avoid them. It took one week of recording “I went in to Berit at the office and asked if she wanted to join me and she said yes straight away.” He contacted the chair of the organisation, who also liked the idea. It took only a week for them to record their films. In four video clips they address basic facts about different infections and their physiological effects, and give the athletes practical tips for staying healthy before and during their stay in the Olympic village. “You can’t protect yourself against every eventuality, but there are some simple tricks that can make a big difference, and that’s what we want to get across,” says Dr Carow. The idea is that the films will make sportspeople think about and discuss health matters. They can then contact both KI researchers, who will be available online to give their expert advice. Because experts is what they truly are. Dr Carow has an impressive CV: she just missed bronze in the double scull (rowing) event in Peking in 2008 and has won several World Championship medals for Germany. And even though she has cut down on the competitions since moving to Sweden, she still rows. Competition for all on equal term Dr Chambers has had a long career as a fencer for the Irish national team and has competed in many world and European championships. He still fences competitively, but no longer at an elite level. He adds that he was in the qualifiers for Rio, but failed to make it all the way. “I knocked out the silver medallist from the London Olympics, which was great, but the next day he announced on TV that he was quitting. Lose against Benedict and there’s clearly no point carrying on,” he says with a laugh. They like the thought of not just being spectators at the coming Olympics. “We’re doing this a lot for the smaller teams that aren’t able to bring their own doctors,” says Dr Carow. “We want to make the information simple and accessible to all and to contribute to the Olympic philosophy – competition for all on equal terms,” she continues. Text: Mårten Göthlin Translation: Neil Betteridge Photo: Gustav Mårtensson   Brief facts about the Rio Olympics *A record number of countries and participants are expected: over 10,000 from 206 countries. *The Swedish Olympic Committee is sending approx. 150 competitors. *Rio will be the first South American Olympic host ever. *28 Olympic events – two more than in London 2012 (newcomers are golf and seven-aside rugby). *To be held from 5 to 21 August 2016. Sources: www.rio2016.org, SOK.

Professor Christer Betsholtz is the new director of AstraZeneca and Karolinska Institutet joint Integrated Cardio Metabolic Centre (ICMC) based at KI . "To me, the ICMC represents a unique type of platform for academia-industry collaboration that I am certain will deliver fundamental knowledge suitable for the translation into new therapies. I look forward to working closely together with ICMC’s many talented researchers and help building their networks and collaboration with AstraZeneca scientists and academic institutions worldwide.” says Christer Betsholtz. Betsholtz is a leading scientific authority in the field of vascular biology with more than 300 publications. He is currently professor with tenure both at Uppsala University and Karolinska Institutet and will maintain his professional appointment and a significant research presence at Uppsala University. Professor Betsholtz will also take up a part time position as Chief Scientist at AstraZeneca. Through the synergies of these roles, he will provide a day-to-day link between the ICMC, the universities and AstraZeneca. Centre established three years ago Karolinska Institutet and AstraZeneca established the Integrated Cardio Metabolic Centre in 2013, with the aim to identify and validate novel targets within cardio metabolic diseases, focusing on three strategic research areas: heart failure, diabetes and chronic kidney disease across both small molecules and biologics. The collaboration goes deeper than the usual industry-academia partnership, as scientists from both partners work side-by-side in a dedicated university unit to develop new therapies for people in need.  “Christer Betzholtz is a world renowned scientist in his field. He is also a great leader and mentor. He is committed to raising ICMC to the next level, where we will be working more on joint projects, publishing more joint publications and truly establish ICMC as world leading in scientific excellence.” says Menelas Pangalos, Executive Vice President, Innovative Medicines & Early Development at AstraZeneca. When the collaboration was announced in 2013, the contract was initially for five years. The collaboration has since then been prolonged until 2020. Uniquely powerful collaboration Acting Vice-Chancellor at Karolinska Institutet, Karin Dahlman-Wright, says: “It has become increasingly clear that industrial and academic scientists provide complementary skills that are needed to meet current challenges in medicine and health. Although we have been leading in biomedical sciences, we need partnerships in order to develop new therapies for patients. This collaboration is uniquely powerful as it goes beyond traditional partnerships.” Under the leadership of Christer Betsholtz, ICMC intends to become a hub for building fruitful networks within cardio metabolic diseases in Sweden and globally, tapping into frontline scientific excellence. ICMC will endeavor to draw on nature’s own solutions to regeneration to develop regenerative medicine therapies to meet today’s unmet medical needs in diseases such as heart failure and diabetes.

The nomination process for Karolinska Institutet’s next vice-chancellor is underway, and this summer an application committee will be seeking out candidates before the interview process commences in August. Before the previous recruitment process for KI’s vice-chancellor in 2012, KI decided to adopt a broader, more active search process. People talked about a paradigm shift, and about how the position of vice-chancellor has become more demanding and complex. The expectations of the next vice-chancellor are even tougher. Anders Hamsten resigned at his own request after the storm of criticism kicked up by the Macchiarini documentary Experimenten. This autumn, the inquiries into how KI handled the case will present their reports, which will land on the new vice-chancellor’s desk. “Proactive leader” The University Board chairperson, Lars Leijonborg, who also chairs the election committee, talks about KI needing a “proactive leader” and a strong academic representative. “In the first sentence of the requirement profile, we make it explicitly clear that KI is looking for a new vice-chancellor who is an acknowledged academic leader, but we also envisage an eminent researcher with a great deal of personal integrity,” says Lars Leijonborg. “There are many strong opinions and wills at KI, and a vice-chancellor must be able to resist them.” Just like last time, an application committee has been asked to facilitate the recruitment process by finding interesting candidates and explaining what Karolinska Institutet expects of a vice-chancellor. Their net will be cast globally as they search for candidates not only through nominations but also by consulting with the HR Office and combing their own networks. “We’ll be looking at external as well as internal candidates,” says Professor Sven-Erik Dahlén, co-opted member of the application committee. Consultative College gives opinions The bridge between the application committee and the University Board is the election committee, a small collective comprising members of the board who lead and coordinate the work. The election committee will eventually pass its proposed candidates to the board, who will then decide on what name to submit to the government for its final decision. First, however, KI as a whole is to give its opinions through the Consultative College, which represents its faculty, non-teaching staff and students. The body will have a more influential role than before. The Consultative College has been involved in the drafting of the requirement profile and its opinions have been influential. The profile is more detailed than previously, according to Erika Franzén, staff representative in the election committee: “There’s more talk about responsibility and organisational role, and about the complexity of leading KI as a vice-chancellor vis-à-vis the outside community and the rest of the world,” she says. Swedish not a requirement A new development is that the person does not need to speak Swedish; he or she does, however, need a “good understanding of how a medical university interacts with the healthcare sector”. Other requirements are that he or she must be internationally known, pedagogically highly skilled and sufficiently familiar with medicine as a discipline. There is also an emphasis on good communication skills and “high ethical demands”. “The demands placed on a vice-chancellor at KI are incredibly high, and it’s a very hard job finding the right person. I hope we’ll have a good pool of candidates to choose from – after all, we’re searching around the world,” says Elias Arnér, faculty representative in the election committee. The open nomination period will end on 15 August. Text: Madeleine Svärd Huss Important dates: 1 June–15 August: Open nomination period for the position of vice-chancellor. August and autumn semester 2016 onwards: Selection of candidates and interviews. Consultative College vote and University Board decision. November 2016 at the earliest: Government decides on a new vice-chancellor on the board’s proposal. January–March 2017: New vice-chancellor takes up office.  

Karolinska Institutet will review six of its international top recruitments funded with special grants from the Swedish Research Council. The review follows a recent decision by the Research Council to decrease the originial grant, due to KI not fully complying with the grant conditions. The councils' decision regards a recruitment where KI did not manage to set up the planned research project in time and hence the recruited researcher was granted leave from the position at KI. However, accordning to the grant conditions the researchers shall work at least 50 per cent at thte university during the time of the grant. The researcher in question is one of six researchers at KI recruited with grants from the Swedish Research Council's grants for the recruitment of distingquished researchers. KI's vice-chancellor has assigned the university's grants office the task of reviewing that all recruitments are in compliance with the stipulated grant conditions.

With its EIT Health programme, the EU is investing in innovative solutions to ageing and health. Karolinska Institutet wants to encourage its students and staff to cultivate an innovative and entrepreneurial mentality. “We want to make much more use of the research being done and show the students the potential of innovation,” says Inger Lundqvist, project manager at Karolinska Institutet’s Innovation Office. Ms Lundqvist’s job is to coordinate all three parts of EIT Health at KI: research, education and entrepreneurship. EIT Health is an EU-financed programme involving top European universities, leading caregivers and companies. It is hoped that the closer collaborative links between research and industry thus formed will give rise to new innovations able to promote a healthy life, active ageing and more effective care. “EIT Health is one of several initiatives that KI has taken on innovation and entrepreneurship,” she says. It is hoped that in the long run the project will help to improve the quality of life and healthcare services in Europe by introducing newly developed products and services. “One of the greatest challenges facing society is the ageing population,” says Professor Jan-Olov Höög, Scandinavian director for EIT Health Education. “Elderly people need to live a more active, healthier life if they’re to keep the doctor away.” If the integration of entrepreneurship, research and higher education becomes more natural, it will be easier to produce more innovations more quickly. “We want to get new innovative companies up and running that focus on the health of elderly people,” says Professor Höög. It is hoped that EIT Health projects around Europe will come up with 80 new entrepreneurial ideas by the end of 2016, and that by 2018 there will be 70 new start-ups a year. The degree of success of the project will depend on getting the students on board. “We want the students to become acquainted with entrepreneurship so that they are equipped to take on the major challenges of the future,” says Professor Höög, who points out that a government order is already in place that all education programmes are to have entrepreneurship on the syllabus. There are already a number of educational activities being run under the EIT Health programme at KI, including the Innovation Day on 18 November at which students will be able to work in teams to tackle real challenges from companies and develop innovative solutions. There will also be a competitive element to make it that little bit more exciting. “In Stockholm we had a workshop at the end of April with over 30 participants, including students, teachers, researchers and a company representative, who provided the actual challenge,” says Hanna Jansson, head of the Unit for Bioentrepreneurship and the Starter Lab. The next stop on the workshop’s European tour is Lisbon on 6-8 October. “It’s also a contest, but the idea is not to get hung up on winning but to take part in and learn from the process,” says Dr Jansson. Three vital areas for EIT Health: Promoting healthy lifestyles Supporting active ageing Improving healthcare   TEXT: Maja Lundbäck

People with malignant melanoma with an inherited mutation in a certain gene are twice as likely to die of the disease, according to a new study carried out by researchers at Karolinska Institutet and Lund University in Sweden. The finding, which is published in The Journal of the National Cancer Institute, suggests that individuals with familial melanoma who have the mutation should be monitored particularly closely. Exposure to the sun is a key risk factor of malignant melanoma, one of the fastest growing cancers in the West. Often, however, heredity plays an important part as well. Roughly one in ten people with familial melanoma has a mutation in a gene called CDKN2A, a so-called tumour-suppressor gene, which prevents cancer cells from developing in the body. Increase risk It has been known since the mid-1990s that mutations in this gene greatly increase the risk of developing malignant melanoma. Researchers have previously shown that people with a CDKN2A mutation also have an elevated risk of smoking-associated cancer in the airwaves and upper digestive organs. In the present study, the researchers show for the first time that mutations in the gene also affect survival rates for melanoma. “We found that the individuals who had an inherited CDKN2A mutation were on average ten years younger when diagnosed with melanoma than those with familial melanoma but no mutation,” says co-author Hildur Helgadottir at Karolinska Institutet’s Department of Oncology-Pathology. “However, despite the fact that lower age at diagnosis usually is a protective factor, they run more than twice the risk of dying from their melanoma. They are also seven times more likely to die of another cancer than non-carriers of the gene mutation.” The shorter survival time amongst mutation-carriers remains when adjusted for other examined factors that might affect the progression and survival from the disease, including thickness of the skin melanoma. Undiscovered factors The researchers argue that this suggests the presence of still undiscovered biological factors in the tumours of individuals with CDKN2A mutations that make them more aggressive than those of non-carriers. “These findings emphasize the importance of including CDKN2A mutation-carriers in preventive health programmes. The aim is to prevent the development of tumours by giving advice on healthy sun-habits and promote abstinence from tobacco use and also to identify tumours at as early stages as possible and to discover any relapses before they become untreatable,” says Dr Helgadottir. Since the 1980s, Swedish families with multiple cases of malignant melanoma have been included in a preventive programme. In this study, the researchers linked data on CDKN2A mutations in these family members to data from Swedish health and population registries. In this way comprehensive information on all cancer types that had been diagnosed along with information on all registered deaths was obtained to ascertain if there is a link between the mutation and survival. The study was financed with grants from several bodies, including the Swedish Cancer Society and the Cancer Research Funds of Radiumhemmet. Publication Germline CDKN2A mutation status and survival in familial melanoma cases Hildur Helgadottir, Veronica Höiom, Rainer Tuominen, Kari Nielsen, Göran Jönsson, Håkan Olsson, Johan Hansson Journal of the National Cancer Institute, publicerad online 10 juni 2016, doi: 10.1093/jnci/djw135

Oligodendrocytes, a type of brain cell that plays a crucial role in diseases such as multiple sclerosis, are more diverse than have previously been thought, according to a new study by researchers at Karolinska Institutet in Sweden. The findings, published in the journal Science, will help increase our understanding of diseases in which these cells are affected and possibly provide clues to future treatment strategies. In multiple sclerosis and similar neurological diseases, the electrical signals in the brain propagate more slowly. The reduced speed of information flow contributes to symptoms such as numbness, balance and walking difficulties and blurred vision. Loss of myelin Multiple sclerosis is characterised by the loss of myelin, a protective sheath that insulates nerve cells and allows rapid transmission of electrical signals in the brain. Myelin is produced by a specialized cell type, the oligodendrocyte. While oligodendrocytes have thus far been thought to be a homogenous population, a different view emerges from the current study. The researchers, led by Dr. Gonçalo Castelo-Branco and Dr. Sten Linnarsson, used the recently developed technique of single cell RNA-sequencing. This method allows investigators to get a snapshot of gene activity in individual cells. In this way, they could reveal differences between cells that may not be visible using classical methods. The researchers analysed more than five thousand oligodendrocytes from several regions of the brain and spinal cord in adolescent and adult mice, which allowed them to see the diversity of these cells with unprecedented detail and clarity.  ”We uncovered an unexpected diversity within the oligodendrocyte population”, says Sten Linnarsson from the Department of Medical Biochemistry and Biophysics. ”In this study, we have identified 12 subclasses of oligodendrocytes and a novel cell distinct from oligodendrocytes residing in the blood vessels” Specific regions They found that the initial stages of maturation in oligodendrocyte development were similar across the central nerve system in juvenile mice, whereas different subsets of mature oligodendrocytes were enriched in specific regions in adult brains. ”The uncovering of this unexpected oligodendrocyte diversity might bring new insights on mechanisms of degeneration and regeneration of diseases where myelin is lost, such as multiple sclerosis”, says Gonçalo Castelo-Branco at the same department. The research has been supported by, among others, the Swedish Research Council, Swedish Brain Foundation (Hjärnfonden), Swedish Society of Medicine (SLS), Åke Wiberg, Clas Groschinsky, Petrus och Augusta Hedlunds foundations and European Union. Publication Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system Sueli Marques, Amit Zeisel, Simone Codeluppi, David van Bruggen, Ana Mendanha, Falcão, Lin Xiao, Huiliang Li, Martin Häring, Hannah Hochgerner, Roman A. Romanov, Daniel Gyllborg, Ana Muñoz Manchado, Gioele La Manno, Peter Lönnerberg, Elisa M. Floriddia, Fatemah Rezayee, Patrik Ernfors, Ernest Arenas, Jens Hjerling-Leffler, Tibor Harkany, William D. Richardson, Sten Linnarsson, Gonçalo Castelo-Branco Science, published online 10th of June 2016, doi 10.1126/science.aaf6463.

In the spring of 2016, KI researcher Tore Curstedt was nominated for a Lifetime Achievement Award by the European Patent Office for having devoted his life to Curosurf, a drug that has helped to activate the lungs of millions of preterm babies. Tore Curstedt is now retired but turns up almost daily to his office at Karolinska University Hospital. The room is plainly furnished, with shelves of files, light-wood table tops and chairs upholstered in blue. “You can’t just stop working when you realise that all the research you’ve sweated over has maybe saved the lives of half a million babies,” he says. Every morning, he gets off the bus a few stops from the university and walks the rest of the way through the northern cemetery, passing by the gravestones of Alfred Nobel, Ingrid Bergman, Ernst Rolf and Folke Bernadotte, to name just a few of the great Swedes resting there. “I walk through the different plots memorising the names on the stones and the places where famous people lie. It’s a bit of morning exercise for both brain and body,” he chuckles. Tore Curstedt was born in 1946, the only child in the Piteå household. His father was a mental health nurse and his mother a housewife. He obtained such good school grades that he could start considering medical studies, so he applied to Karolinska Institutet, enticed not only by the programme but also by the thought of scientifically studying the workings of the body to understand his own intestinal health problems better. And thus he embarked on his medical career. He was in his teens when the papers were writing about President Kennedy’s son, who, in spite of the USA’s medical expertise, died in a Boston hospital just a few days old from lung failure. Back then, ninety percent of preterm babies died. It is not unlikely that it was then the seed of a challenging thought was planted in Tore Curstedt’s mind. A drug able to activate the lungs of preterm babies Teaming up with fellow-researcher Bengt Robertson, he conducted experiments at Karolinska University Hospital to produce a drug able to activate the lungs of preterm babies. The drug was called Curosurf – Cu as in Curstedt, Ro as in Robertson, and Surf as in Surfactant, the substance that in healthy, fully developed humans regulates surface tension in the lungs and prevents them from collapsing on exhalation. A substance that very premature babies have not had time to develop. His partner Bengt Robertson died in 2008, but Tore Curstedt has continued to research. He never forgets an occasion over forty years ago when the two of them received a phone call from a doctor at the neonate ward at St Göran’s Hospital. It was an emergency: a preterm baby girl was dying because her lungs, despite their desperate attempts to save her, were failing to start. With only hours to go, the doctors and the girl’s parents agreed that it was worth one last shot, even though the drug had not been fully developed or even tested on humans. They had successful animal trials behind them, but had yet to reach the stage of human trials and ethical review permits. The attempt was signed and approved by all concerned and what happened a few hours later seemed to them nothing short of a miracle. The drug was injected into the girl’s trachea and in no more than five minutes her blue pallor changed to pink before settling into a normal oxygenated hue. “An hour later her lungs were working normally and we could take her off the oxygen,” says Tore Curstedt. “It was one of the most magical moments of my life. That was it - there was only one way to go: forward!” Swedish industry turned them down But it was hard getting the industry to listen. Pharmacia turned the drug down – too high marketing costs and too small a market, they said. And finding Karolinska Hospital also rather diffident, Curstedt and Robertson turned to Europe. In Italy they found a private drug company, Chiesi Farmaceutici, that was willing to take on the product and patent it. Curstedt and Robertson received royalties. “If we’d been a bit more money-minded we’d have become multimillionaires almost overnight,” says Dr Curstedt, “But that doesn’t bother me. When I meet young people and the parents of children who all want to thank me, even hug me, that’s payment enough for me.” Over the years, scientists have tried to synthesise surfactants. But so far, no one has come close to Curosurf’s successful solution that uses biological material extracted from pig lungs. While the drug was being developed, pig lungs could be obtained for free from Swedish abattoirs; despite this, the process is a costly one, as the pig lung yields just a fraction of a gram, enough for two, maybe three babies. “We’re therefore trying to develop a synthetic solution so we don’t have to rely on pigs,” says Tore. “It’ll take some years, and I hope I’m there all the way to the point when this particular scientific nut is cracked.” People come up to thank him Curstedt and Robertson’s invention is estimated to have helped three million babies and saved the lives of at least half a million preterm babies around the world. The oldest are today in their thirties, and the medicine is sold in around 80 countries. Tore Curstedt emanates deep emotion and pride when he talks about these people, who are all alive today thanks to Curosurf. “I meet them now and again. They come up to me and thank me. One girl who was saved even competed in a memory contest on TV. So sure you can have a perfectly normal life thanks to Curosurf, even if you were born at 28 weeks.” Text: Matts Heijbel Translation: Neil Betteridge Photo: EPO Short facts: Tore Curstedt Age: 70. Work: Docent at the Department of Molecular Medicine and Surgery in the “Clinical chemistry and coagulation” research group at Karolinska Institutet and Karolinska University Hospital. Family: Wife Sol-Britt Curstedt, also a doctor. Two adult children and five grandchildren. Lives in: Edsviken, Sollentuna. Interests: Golf, shares and travel. He has been to over 100 places around the world, including Svalbard, North Korea, Antarctica, Burma and Transnistria. Find out more about the finalist and the winner of EPO Lifetime Achievement.

The risk of asphyxia in a second child is higher if the mother has put on weight since the birth of her first child, according to a new large Swedish registry study conducted by researchers at Karolinska Institutet and published in PLOS Medicine. The results show that a more substantial weight gain between two pregnancies, even in women of normal weight,  increases risks of neonate complications. Offspring of overweight or obese mothers run a higher risk of perinatal complications. Asphyxia in the baby at birth is one such complication. Increased risk While it is already known that  high maternal BMI increases the risk of asphyxia-related injuries in the neonate, the present study is the first to examine if weight-gain between two pregnancies increases the risk of asphyxia in the second baby. “We found that the weight-gain between pregnancies increased the risk of  asphyxia in a woman’s second baby,” says Martina Persson, researcher and paediatrician at Karolinska Institutet’s Department of Medicine (Solna) and at Sachs’ Children and Youth Hospital. “This was particularly salient in children of mothers who were of normal weight at the time of their first pregnancy, but who had put on weight by their second.” The researchers used data from the Swedish Medial Birth Registry on over half a million mothers who had had their first and second babies between 1992 and 2012. Examined associations The health of all neonates is assessed shortly after birth using the Apgar Scale. The researchers examined associations between inter-pregnancy weight-gain and asphyxia-related complications in the second baby  (as expressed as a low Apgar score five minutes after delivery, seizures or severe breathing difficulties during the neonatal period). Several obesity-related conditions, such as chronic hypertension, preeclampsia and diabetes are themselves linked to complications in neonates, but interpregnancy weight gain increased risks of asphyxia-related complications even when the researchers excluded women with these diseases. “Weight gain between pregnancies also increases risks of other complications related to pregnancy and infant health. The take home message is that after delivery, women should be advised to return to their prepregnancy weight,” says Dr Persson. More than one in every three women who give birth in Sweden are overweight or obese. The study was financed by the Swedish Research Council for Health, Working Life and Welfare and by an unrestricted grant from Karolinska Institutet. Dr Persson has a clinical post-doc position financed by Stockholm County Council. Publication Inter-pregnancy Weight Change and Risks of Severe Birth-Asphyxia-Related Outcomes in Singleton Infants Born at Term: A Nationwide Swedish Cohort Study Martina Persson, Stefan Johansson, Sven Cnattingius  PLOS Medicine, published online 7 June 2016

Obesity is a risk factor for developing type 2 diabetes, yet not all obese humans develop the disease. In a new study, published in the journal Nature Medicine, researchers from Karolinska Institutet in Sweden and the Institute of Health and Medical Research (INSERM) in France have identified epigenomic alterations that are associated with inflammation and type 2 diabetes.  The findings help to explain how alterations of the epigenome during the progression of obesity can trigger insulin resistance and diabetes. Obese individuals differ in their susceptibility to developing insulin resistance and diabetes. Researchers believe that changes in the epigenome could be an important reason behind this difference. Dynamic Epigenetic alterations increase or decrease gene expression by coupling different kinds of chemical flags to the DNA and to the histone proteins that constitute the chromatin. In contrast to the genes themselves, epigenetic alterations are dynamic and can be altered by environmental influences and nutritional components. The research team, led by Eckardt Treuter and Nicolas Venteclef, were interested in a so-called co-repressor complex that can modify chromatin epigenetically. This particular complex contains GPS2 (G-protein pathway suppressor 2). The study reveals a key role of the GPS2 complex in controlling the epigenome in macrophages. Macrophages play a central role in the immune defense, but are also involved in the metabolically-triggered low-grade inflammation associated with metabolic diseases, including obesity and type 2 diabetes. High-fat diet Initially, the INSERM team had found that GPS2 levels are reduced in the adipose tissue in obese people with diabetes, as compared to non-diabetic people. As it turned out, the identified obesity-associated alterations are conserved between humans and mice. The Karolinska team had generated mice that lack GPS2 in macrophages. When fed with a high-fat diet, these genetically modified mice did not become more obese than normal mice. However, they developed complications such as adipose tissue inflammation, systemic insulin resistance, and fatty liver, more rapidly. The characteristics observed in these mice mirror the human situation of “metabolically healthy” versus “unhealthy obese” people, according to the authors. ”The findings point to a causal and potentially reversible relationship between inappropriate expression and function of the complex, the extent of adipose tissue inflammation, and systemic insulin resistance towards type 2 diabetes”, says Nicolas Venteclef at the Cordeliers Research Centre, INSERM, in Paris. ”The study highlights the value of combining mouse and human studies in identifying molecular mechanisms underlying disease”, says Eckardt Treuter at Karolinska Institutet’s Department of Biosciences and Nutrition in Huddinge, South Stockholm. ”In particular, the mouse experiments provide strong evidence that epigenome alterations that originate in either macrophages or fat cells can be the cause, and not just a consequence, of obesity complications towards diabetes.” The investigators believe that these alterations could be part of an ’epigenetic memory’ that can speed up an inflammatory response under conditions of metabolic stress linked to obesity and diabetes. The research was supported by grants from, among others, the Swedish Research Council, the French National Agency of Research, the Swedish Cancer Society, the French Foundation for Medical Research, the Novo Nordisk Foundation, the Swedish Diabetes Foundation and the French and European Diabetes Foundations. Publication Loss of the corepressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes Rongrong Fan, Amine Toubal, Saioa Goñi, Karima Drareni, Zhiqiang Huang, Fawaz Alzaid, Raphaelle Ballaire, Patricia Ancel, Ning Liang, Anastasios Damdimopoulos, Isabelle Hainault, Antoine Soprani, Judith Aron-Wisnewsky, Fabienne Foufelle, Toby Lawrence, Jean-Francois Gautier, Nicolas Venteclef and Eckardt Treuter. Nature Medicine, online 6 June 2016, doi: 10.1038/nm.4114.

Compared with the early 1990s, babies born with Down syndrome (trisomy 21) have a lower risk of developing serous heart problems, according to a new registry study from Karolinska Institutet published in Pediatrics, the journal of the American Academy of Pediatrics. The reason for this improvement is not known, but the researchers believe there to be a likely connection with fetal diagnostics. To perform their study, the researchers accessed the national Medical Birth Registry, the Birth Defects Registry and the Patient Registry. Amongst the 2.1 million babies born between 1992 and 2012 were almost 2,600 with Down syndrome that were further studied with regard to congenital heart defects. The risk dropped Even though half the babies with Down syndrome had some sort of congenital heart defect, the researchers found that the risk of complicated heart defects dropped sharply during the study period. “The risk of complicated heart defects that usually require surgery, was 40 per cent lower at the end of the study period,” says the project’s initiator Stefan Johansson, consultant at Sachs’ Children and Youth Hospital and researcher at Karolinska Institutet’s Department of Medicine in Solna. “We also observed a shift in incidence ratios, with the decrease in complicated heart defects being matched by an increase in less severe heart defects.” While the project was not designed to analyse causal relations, the group speculates that the result might be attributable to fetal diagnostics. If routine ultrasound reveals a heart defect, the parents usually opt to have the fetus checked for chromosome abnormalities. If Down syndrome is then diagnosed, it is not uncommon for the pregnancy to be terminated, which could account for the drop in the number of babies born with severe heart defects. Selection effect Another possibility is that prenatal tests for Down syndrome, which are usually offered to older women, lead to a selection effect if the age of the mother impacts on the risk of heart defect in the fetus. “The fact that babies born with Down syndrome have healthier hearts than they used to is good news for the families, many of whom find it very tough at first after the baby is born,” says Dr Johansson. “I also hope that our research makes a positive contribution to the public conversation on Down syndrome, which centres mainly on fetal diagnostics. I agree with many parents of these children that the discussion is too tainted by the abortion issue, as if people with Down syndrome don’t have the same right to life as others. Which of course they do!” It is unknown whether today’s generation of children with Down syndrome are healthier in other respects too. The research group plans to examine if other common diseases associated with the condition, such as infection sensitivity and hypothyroidism, have also become less common. The study was financed with grants from the Samaritan Foundation and Sällskapet Barnavård (the Child Welfare Society) in Stockholm. Publication Trends in Congenital Heart Defects in Infants with Down Syndrome Sofie Bergström,  Hanna Carr, Gunnar Petersson, Olof Stephansson,  Anna-Karin Edstedt Bonamy,  Anders Dahlström, Cecilia Pegelow Halvorsen, Stefan Johansson Pediatrics, published online 1 June 2016, doi: 10.1542/peds.2016-0123

The 2016 Global Swede award goes to KI student Hugo Morales. In the two years he has studied at Karolinska Institutet, he has not only distinguished himself academically but also proved adept at creating networks. This is the successive year of the Global Swede award, which is presented to international students who have distinguished themselves through their innovative spirit and entrepreneurship. Hugo Morales, who is on the final semester of a master’s degree in bioentrepreneurship, was nominated by Karolinska Institutet. “It’s such an honour to be recognised for what I’ve achieved as a student at KI,” he says. The Global Swede award is a joint initiative by the Swedish Institute and the ministries of Enterprise & Innovation and Foreign Affairs. Mr Morales received his diploma along with 21 other students at a ceremony on 18 May from the hands of Oscar Stenström, state secretary at the Department of Enterprise and Innovation.  “Overseas students are a valuable asset for Sweden in terms of growth and future competitiveness,” Mr Stenström declared during the ceremony. “Apart from contributing new knowledge and perspectives, they are also a vital resource for building bridges between Sweden and the rest of the world.” Hugo Morales has been studying at KI for almost two years, having entered tertiary education back at home in Mexico. Also attending the ceremony was the Mexican ambassador, with whom he was able to network: “It was really great to meet the ambassador,” he says. “I hope there’ll be more such exchanges between students and researchers. It was also a fantastic opportunity to meet the other students and tell them about my work.” In KI’s statement explaining its choice of nominee, Hugo Morales is praised as a “social entrepreneur” possessed of an “inclusive leadership” style. “To my mind it’s about creating value through people’s skills and abilities,” he explains. “I like helping other students to grow and to see them swap skills with each other. And I always try to integrate every member of a team.” At present, Mr Morales is in Germany where he is writing his master’s dissertation “Regulatory environment and margins as market entry factors for small and mid-sized enterprises”. Although he is reaching the end of his education, Mr Morales has still not decided what his next step will be or even whether he will remain in Stockholm. “I want to either start my own company or work for a company committed to creating value in our society rather than just making a profit,” he says. For more information, please view the Swedish Institute's website. Text: Maja Lundbäck

Karolinska Institutet has signed an agreement to support stipends for post-doctoral students from the Regional Centre for Biotechnology (RCB) in India. The agreement is intended to promote collaborations in several projects in translation medicine and innovation at the Center for Molecular Medicine (CMM), Karolinska Institutet. The post-doc program is for one year with the possibility of extension for another year after an evaluation process. - This initiative will increase the collaboration between CMM and research groups in India and serve as a platform for newer ways to innovate and commercialize scientific ideas to products, says Sanjeevi Carani, researcher at CMM, Karolinska Institutet. The program is planned to start in the fall of 2016, after the selection process and the first Indian researchers scheduled to arrive in CMM before the end of the year. More information about Karolinska Institutet’s collaboration with India.

EMBO today announced that 58 researchers in the life sciences has been elected as members of the organization. One of these newly elected members is Óskar Fernández-Capetillo from Karolinska Institutet. Every year new members are elected to EMBO, based on their contributions to scientific excellence. KI researcher Óskar Fernandéz-Capetillo, Professor at the Department of Medical Biochemistry and Biophysics and also affiliated to SciLifeLab, is one of the elected this year. The appointment is a tribute to his research and achievement. Of the other elected scientists 50 are from 13 European countries and the other eight come from China, Japan, Lithuania, Singapore and USA. EMBO is an organization of more than 1700 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work. More reading: Óskar Fernández-Capetillo – he wants to have fun

Researchers at Karolinska Institutet have generated antibodies that reprogramme a type of macrophage cell in the tumour, making the immune system better able to recognise and kill tumour cells. The study, which is published in the journal Cell Reports, could lead to a new therapy and provide a potentially important diagnostic tool for breast cancer and malignant melanoma. Immunotherapy, in which the immune system is enhanced in order to kill tumour cells, especially the kind designed to activate the immune system, is changing the way we treat cancer. Unlike other forms of cancer therapy, immunotherapy targets not the tumour itself but specific cells in the immune system to unleash the ability of the immune system to kill the tumour.   “We’ve found a new way of using antibodies for immunotherapy that activates immune cells, called macrophages, in the tumour,” says research team member Mikael Karlsson at the Department of Microbiology, Tumor and Cell Biology. “This makes it easier for the immune system to recognise the tumour and animal studies of three different cancers have given promising results.” In 2013, the leading scientific journal Science called cancer immunotherapy the year’s most groundbreaking advancement. Antibodies that increase the ability of T-cells to kill tumour cells have proved particularly effective and created new opportunities for treating previously untreatable cancer. Not sufficiently effective However, for some patients, T-cell modified immunotherapy has not been sufficiently effective, as some tumours still manage to conceal themselves from the immune system by emitting signals that prevent the immune cells from recognising them. Another reason for the occasional failure of the therapy is that tumours do not trigger as strong an immune reaction as, for example, infections do. For the present study, the researchers focused on macrophages, immune cells whose normal function is to combat infection. Some macrophages, however, affect their environment in the tumour in a way that makes it easier for cancer cells to survive and spread. Commonly dominant in tumours is a type of macrophage that prevents T-cells and other immune cells from recognising and killing cancer cells. Stopped the tumours The researchers managed to reprogramme and activate these macrophages by using an antibody targeted at a protein on their cell surface, which stopped the tumours from growing and spreading in mice. The antibody therapy also  boosted a type of T-cell-modifying immunotherapy in clinical use. The researchers also show that this type of macrophage can be found in human breast cancer and malignant melanoma, and therefore hope to be able to develop an antibody that can one day be used for treating these patients. “We now hope that this new therapy, which has so far been tested preclinically, will one day be used in combination with another immunotherapy to make it even more efficacious,” says Professor Karlsson. “We are also looking into  whether the presence of this type of macrophage in human tumours can be used clinically for the diagnosis of cancer diseases.” Lead author of the study has been Anna-Maria Georgoudaki. The study was financed with grants from the Swedish Research Council, the Swedish Cancer Society, the Strategic Research Programme in Cancer at Karolinska Institutet (Stratcan) and Rockefeller University. Publication Reprogramming tumor associated macrophages by antibody targeting inhibits cancer progression and metastasis  Anna-Maria Georgoudaki, Kajsa Prokopec, Vanessa F. Boura, Eva Hellqvist, Silke Sohn, Jeanette Östling, Rony Dahan, Robert A. Harris, Mattias Rantalainen, Daniel Klevebring, Malin Sund, Suzanne Egyhazi Brage, Jonas Fuxe, Charlotte Rolny, Fubin Li, Jeffrey V. Ravetch and Mikael C.I. Karlsson  Cell Reports, published online 19th of May 2016. 

Keep your roles as academic researcher and entrepreneur separate, advises Klas Wiman. Thirteen years ago he started a company based on a substance that induces apoptosis in cancer cells. Now the project has reached clinical phase II and the company recently received SEK 430 million. The p53 protein normally protects against cancer by making sure that damaged cells commit suicide or stop dividing. However, the gene for p53 can be mutated, creating a p53 protein that fails to work and that causes the cells to continue on a path of uncontrolled growth. In roughly half of all tumours, the p53 gene is mutated. In 1999, Professor Klas Wiman from the Department of Oncology-Pathology and his colleagues Vladimir Bykov and Galina Selivanova found a molecule that returns proper functionality to the mutated p53 protein. Tumour cells with mutated p53 died when the molecule was introduced, while healthy cells were hardly affected. The researchers submitted a patent application with the help of KI Innovations, and the results were published in Nature Medicine. Klas Wiman explained to the world’s media about the substance that recreated p53 function and induced apoptosis in cancer cells – then an entirely novel concept. Keeping the roles apart In 2003 they founded the company Aprea with KI Innovations. While Klas Wiman has been on the board since inception, the company has always been led by people with industrial experience of drug development. “I want to be an academic researcher,” he says. “Running a company requires different skills. It’s better if we scientists continue our research on p53 and its mechanisms of action.” Klas Wiman is convinced that it is important for the founders to continue their academic research and publishing the results within the field when a company is formed, in the interests of the researchers’ careers and attractiveness to financiers, and so that their research can strengthen the company. He also believes that it is important to keep the roles of academic researcher and entrepreneur separate: “You have to be objective when in your academic researcher role, writing articles and speaking at conferences, for example. You don’t have to forego objectivity just because you have a company or a substance that you think is good.” Investors enables phase II study This March, Aprea received SEK 430 million from a group of pharmaceutical investors. The money will be put towards a phase II study in which the company’s candidate substance will be tested on patients with ovarian cancer. “It’s great that we’ve come so far, but it’s still a high-risk enterprise,” he says. “We’ll have to wait and see how it goes.” Professor Wiman or his research has not yet received any money from the company. “I’ve got my holding in the company, but its value drops dramatically when we get in new investors. But then again I’m not in this for the money. I’m doing it because it’s important.”  Text: Sara Nilsson Translated by: Neil Betteridge   Klas Wiman’s advice to researchers starting companies: - Karolinska Institutet Innovations is a vital resource with a wide contact network. Get help from them if you can. ​- Continue to do research and publish results. Strong publications from the founders bolster the company. But make sure that you’ve submitted your patent applications before going to press. Never sign a contract that blocks or unnecessarily restricts your right to publish. - Remember to remain independent in your role as academic researcher, even though you have a company.