Integrative Molecular Phenotyping

KI News

Updated: 1 min 58 sec ago

The election is over – at least for KI

Fri, 05/12/2014 - 13:13
The academic election year at Karolinska Institutet, during which deans, assistant deans and faculty representatives were voted onto the University Board and the three internal boards, drew to a close on 3 December. The deans and assistant deans were elected back in the spring, and on 3 December the identities were established of the faculty members who will be sitting on the boards that the deans will be heading. This means that the boards of Higher Education, Doctoral Education and Research are now ready to set to work for their new term of office that will last from 1 January to 31 December 2017. Earlier in the autumn it was also announced who will be representing the teachers on Karolinska Institutet’s highest executive body, the University Board, from the new year. Elias Arnér will be continuing for another three years, joined by new members Anna Karlsson and Lena Von Koch. All three were elected by KI’s teachers with voting rights in September by means of electronic ballot. The faculty representatives on the internal boards were elected in turn by a nomination assembly comprising 67 departmental representatives. The election of the deans last spring was decided after a consultative election by teachers with voting rights at Karolinska Institutet, whereupon the final decision was taken by Vice-Chancellor Anders Hamsten.  

Nine young researchers awarded Wallenberg Academy Fellows at Karolinska Institutet

Fri, 05/12/2014 - 10:10
The Knut and Alice Wallenbergs Foundation has selected nine researchers from Karolinska Institutet as Wallenberg Academy Fellows 2014. They are to receive funding between SEK 5 and 9 million over five years. Four of the researchers are international recruitments to Karolinska Institutet. Jenny Mjösberg People with a history of inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease, have a higher risk of developing colon cancer. As a Wallenberg Academy Fellow, Jenny Mjösberg will study the role played by a newly discovered family of cells that belong to the immune system, innate lymphoid cells, in the development of tumors. Jenny Mjösberg will share her time between the Department of Medicine, Karolinska Institutet, Huddinge and Linköping University. Read more here Jenny Mjösberg group Björn Högberg Associate Professor Björn Högberg from the Department of Neuroscience, Karolinska Institutet, can control the folding of DNA molecules by programming the genetic code: this is called DNA origami. As a Wallenberg Academy Fellow, he will use DNA origami as a tool for investigating the interactions between cells and mapping the differences in gene expression between healthy cells and cancer cells. Read more here Högberg lab Pekka Katajisto People, who can keep their stem cells young, can keep their bodies young. As a Wallenberg Academy Fellow, Pekka Katajisto seeks methods that will help stem cells to retain their vitality. In doing so, he will try to delay aging. Dr Pekka Katajisto is at the Institute of Biotechnology, University of Helsinki, and Academy Research Fellow, Academy of Finland. He will continue his research at Karolinska Institutet in Stockholm. Read more here Katajisto lab Yenan Bryceson When genetic defects sideline cells of the immune system, serious and often deadly diseases may result. Dr Yenan Bryceson at the Department of Medicine, Karolinska Institutet, and Adjunct Professor at the Department of Internal Medicine, University of Bergen, will use the latest methods in gene technology to map the mutations that disrupt the functioning of two white blood cells: cytotoxic T cells and natural killer cells. The knowledge generated by the project will be used by Yenan Bryceson to develop sensitive diagnostic methods for diseases that are linked to these lymphocytes. The hope is that this also results in better treatment methods. Read more here Yenan Bryceson Group Edmund Loh Each year, around 100 people in Sweden suffer serious meningitis caused by a meningococcus bacterium that is normally found in the nose and throat. For some reason, the bacteria penetrate the mucous membrane and enter the brain. As a Wallenberg Academy Fellow, Edmund Loh will conduct research into why these bacteria suddenly become dangerous.  Edmund Loh is currently Swedish Research Council Postdoctoral Fellow at The Sir William Dunn School of Pathology, University of Oxford. As a Wallenberg Academy Fellow, Edmund Loh will be based at Karolinska Institutet in Stockholm. Read more here Andreas Olsson Researchers know much about how personal experiences of distressing events give rise to fear, but we also learn fear from others and we learn to be afraid of others. What governs these types of social learning? Andreas Olsson, Associate Professor at the Department of Clinical Neuroscience, Karolinska Institutet, will look for the answer to these questions during his time as a Wallenberg Academy Fellow. Read more here Andreas Olsson Group Robert Månsson Sometimes the genetic mutations that cause diseases are located outside the actual genes, in parts of the DNA that regulate the gene’s activity. Dr Robert Månsson at the Center for Hematology and Regenerative Medicine, Karolinska Institutet, will pair genes that influence blood cells with the correct control region in the DNA. The aim is that this will lead to a better understanding of blood cancer. Read more here Robert Månsson Group Peder Olofsson Many common diseases are linked to an overactive immune system and inflammation in the body. Dr Peder Olofsson, from the Feinstein Institute for Medical Research, Manhasset, USA, will investigate a new and revolutionary discovery: that nerve cells regulate the immune system. The aim is to reduce inflammation by modulating the signals that are sent between the nerves and the immune system. As a Wallenberg Academy Fellow Peder Olofsson will setup this research at Karolinska Institutet, Stockholm. Read more here Eduardo Villablanca In inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease, chronic inflammation occurs in the gut when uncontrolled immune responses are misdirected against self,  microbiota-derived and/or environmental antigens. Eduardo Villablanca will find out why: what happens when the dialog between the gut flora, intestinal cells and cells from the immune system is lost. Eduardo Villablanca is Instructor in medicine at Harvard Medical School, Boston, Assistant Immunologist at Massachusetts General Hospital, Boston, and researcher at Broad Institute, Cambridge, USA. He will move his activities to Karolinska Institutet, Stockholm. Read more here Villablanca Lab About Wallenberg Academy Fellows Sweden’s largest private investment in young researchers, Wallenberg Academy Fellows, has announcement 29 new Wallenberg Academy Fellows 2014. The programme is financed by the Knut and Alice Wallenberg Foundation and supports some of Sweden’s, and the world’s, most promising researchers in medicine, natural sciences, engineering sciences, humanities and social science. All the Wallenberg Academy Fellows participate in a mentoring programme that aims to strengthen their academic leadership and to provide them with the knowledge and experience necessary to improve the commercialisation of their research results. The programme’s international element also contributes to the increased internationalisation of the Swedish research environment, thus fulfilling several of the criteria that are in demand to increase the competitiveness of Swedish research.

KI students highly commended for undergraduate paper

Thu, 04/12/2014 - 11:11
Two students from Karolinska Institutet, Mimmi Mononen and Maria Movin, were highly commended by The Undergraduate Awards at the summit meeting in November. The international award body The Undergraduate Awards (UA) recognises and rewards undergraduate students across 25 disciplines, ranging from business and engineering to visual arts and midwifery. Mimmi Mononen was highly commended for her paper on the role of fractalkine in microglia-glioma communication, and Maria Movin for her work on the impact of childhood asthma and atopy on growth in early adolescence. The 120 winners and highly commended entrants, representing 50 universities, were selected from 4,792 submissions. The awards were presented at the 2014 UA Global Summit in Dublin, Ireland, on 21st November. Linnea Jonsson Axelsson and Elin Persson from Karolinska Institutet were also highly commended, but could not attend the summit.

Miia Kivipelto and Jonas Fuxe awarded ”Best PI at KI”

Wed, 03/12/2014 - 10:10
Miia Kivipelto, professor at Ageing Research Center (ARC) and the Department of Neurobiology, Care Sciences and Society (NVS), and Jonas Fuxe, senior researcher at the Department of Medical Biochemistry and Biophysics (MBB) at Karolinska Institutet, have both received the honorable title ”Best PI at KI” 2014 by the KI Postdoc Association. The annual award was introduced this year and postdocs have nominated and voted for the best nominated PIs (Principal Investigators). Among eleven nominees, Miia Kivipelto and Jonas Fuxe received the most and an equal number of votes. In the nominations, it was mentioned that Miia Kivipelto ”has created a cooperative and stimulating work environment, in which her team is motivated, productive and successful”, while Jonas Fuxe was described as ”a great leader who has restored the postdoc's passion for science”. Both were awarded the prize on 14 November at the “Mentoring for success in science” workshop, which was co-organised by Junior Faculty and the journal Nature Genetics.

Increased infant mortality rates among children of overweight women

Wed, 03/12/2014 - 09:09
Children face a greater risk of dying during the first year of life if the mother is overweight. This is the conclusion drawn by a new study from Karolinska Institutet published in the scientific periodical BMJ. In Sweden, around 3 in 1,000 children die during their first year. In a global context, this is one of the lowest infant mortality rates, but there are still ways to reduce infant mortality further, even in Sweden.  One risk factor that should be preventable is overweight and obesity among young women. "Our research shows that risk in children increase as their mothers become increasingly overweight”, says Stefan Johansson, senior consultant at the Sachs' Children's Hospital in Stockholm, and researcher at Karolinska Institutet.  “For an individual woman, regardless of her weight, the risk of her child dying is very small. However, our results are still important from a population perspective, as overweight is common among women of a childbearing age.” Over 1 million women The study is based on data from the Swedish Medical Birth Register and encompasses over 1 million women and their 1.8 million children born in the period 1992–2010. When analysing this extensive set of data, the researchers investigated whether the mothers' body mass index (BMI) in early pregnancy was associated with the risk of the infant death.  Of all the women, 24 per cent were overweight (BMI 25.0–29.9) and 9 per cent were obese (BMI 30.0 and up). An increasing BMI was associated with an increasing rate of infant mortality; from 2.4 cases per 1,000 women of normal weight (BMI 18.5–24.9) to 5.8 cases per 1,000 women with the most pronounced obesity (BMI 40.0 and above). Relatively speaking, the increase in risk was moderate for children of overweight women (BMI 25.0–29.9) or mild obesity (BMI 30.0–34.9), at 25 and 37 per cent respectively. In women with more pronounced obesity (BMI 35.0 and up), the child's relative risk was doubled. In two previous projects, the research group have found that increasing BMI in women increases the risk of premature births and hypoxia during birth; two complications that can lead to the child's death. "However, when we looked at the causes of infant deaths, we realised that there were several different underlying problems,” says Stefan Johansson. “Other than premature birth and hypoxia, congenital abnormalities and diseases during the neonatal period also contributed to the higher mortality rate.” Promote public health The researchers hope their results do not worry women with a high BMI, as it is still rare for infants to die in Sweden. The most important message of this study, according to Stefan Johansson, is the importance of broad-based strategies to promote public health. A healthier society with a population being more normal weight would also be beneficial to the health of newborns. "Another important message relates to antenatal and neonatal care. Deliveries involving overweight women, and especially those with a significantly elevated BMI, should be considered to carry a higher risk”, says Stefan Johansson. “The health service has a responsibility to be particularly observant in these cases, to minimise risks to both mother and child.” Financial support for the study was provided by an unrestricted grant from Karolinska Institutet (Distinguished Professor Award to Professor Sven Cnattingius), and from the Swedish Research Council for Health, Working Life and Welfare. View a press release about this research Publication Maternal overweight and obesity in early pregnancy and risk of infant mortality – a population-based cohort study in Sweden Stefan Johansson, Eduardo Villamor, Maria Altman, Anna-Karin Edstedt Bonamy, Fredrik Granath, Sven Cnattingius British Medical Journal (BMJ) 2014;349:g6572, online 2 December 2014

Causal link between antibiotics and childhood asthma dismissed

Mon, 01/12/2014 - 09:09
In a new register study in the scientific journal BMJ, researchers at Karolinska Institutet are able to dismiss previous claims that there is a link between the increased use of antibiotics in society and a coinciding rise in childhood asthma. The study includes half a million children and shows that exposure to antibiotics during pregnancy or early in life does not appear to increase the risk of asthma. Several previous studies have shown that if the mother is given antibiotics during pregnancy or if a small child is given antibiotics in early life, the child has an increased risk of developing asthma. These studies have led to a widespread belief of a causal link. However, according to the researchers at Karolinska Institutet, there is reason to question the results of these studies. It may be difficult to diagnose asthma in small children since newly presented symptoms of asthma can be misinterpreted as a respiratory infection. The children may then have received antibiotics for the supposed infection – which actually is asthma – and the antibiotic treatment is then suspected to have caused the asthma that is later discovered. Another explanation is that respiratory infections themselves increase the risk of asthma, regardless of whether or not they are treated with antibiotics. A third explanation is that previous studies have not given sufficient consideration to other factors shared within families that may increase the risk of asthma, such as genetics, home environment and lifestyle. Exposed to antibiotics "Thanks to the Swedish population based registers we have been able to conduct a study designed to include factors that were previously not included. Our results show that there does not appear to be a causal link between early exposure to antibiotics and asthma, which is also valuable from an international perspective," says Anne Örtqvist, physician and doctoral student at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet.   The study includes almost 500,000 children born in Sweden between January 2006 and December 2010. As a first step, the researchers studied the children that had been exposed to antibiotics in fetal life, when their mothers were treated during pregnancy, and found that the risk for asthma in the child was increased by 28%. The researchers then included other risk factors such as genetics, home environment or lifestyle by performing comparative analyses within families with several children, and found that the relationship between antibiotics during pregnancy and asthma disappeared. In brief, there were a large number of children in the study where one sibling had asthma and where another had been exposed to antibiotics early in life without developing asthma. The number of such families was large enough to rule out a causal link between antibiotics during pregnancy and asthma in the child, according to the study. Conducted sibling analyses In the next step, children who had received antibiotics early in life were studied. The researchers compared if the risk of developing asthma after treatment with antibiotics was equally high if the child had been treated for a skin-, urinary tract- or respiratory infection. They found that this was not the case. The risk was instead much higher after being treated for a respiratory infection, which indicates that the link was due to newly presented asthma being misinterpreted as a respiratory infection and treated with antibiotics, or that the respiratory infection in itself increases the risk of asthma, regardless of whether or not it is treated with antibiotics.  When the researchers conducted sibling analyses divided by skin-, urinary tract- and respiratory infection, the link between antibiotics treatment and asthma disappeared. "Our results indicate that there is no causal link between antibiotics treatment and childhood asthma. But it is still important to use antibiotics very carefully, considering the threat of antibiotic resistance. We also want to emphasise the importance of correctly diagnosing children with airway symptoms, where suspected symptoms of asthma should be separated from respiratory infection," says Catarina Almqvist Malmros, Pediatrician and Professor at the Department of Medical Epidemiology and Biostatistics, who led the study. The study is financed by project grants from the Swedish Research Council and SIMSAM, grants provided by the Stockholm County Council (ALF project), the Strategic Research Programme in Epidemiology at Karolinska Institutet and the Swedish Heart-Lung Foundation. View a press release about this research Publication Antibiotics in fetal and early life and subsequent childhood asthma: nationwide population based study with sibling analysis Anne K Örtqvist, Cecilia Lundholm, Helle Kieler, Jonas F Ludvigsson, Tove Fall, Weimin Ye, and Catarina Almqvist British Medical Journal, online 28 November 2014, BMJ 2014;349:g6979

Another of this year’s Nobel prizes linked to KI

Mon, 01/12/2014 - 08:08
This year’s Nobel Prize in Chemistry also has strong links to life sciences and to KI. Super-resolution has revolutionised light microscopy and given scientists new tools for studying events at a molecular level in living cells. The limit of light microscopy was calculated back in the 1800s: approximately 0.2 micrometers. Resolution any higher than this was considered a physical impossibility. However, in the past decade this limit has been elegantly circumvented with lasers and fluorescent markers, enabling biologists to study processes in living cells at a much higher resolution than ever before. It is an innovation that has earned Stefan Hell, Eric Betzig and W.E. Moerner the 2014 Nobel Prize in Chemistry. Sweden’s centre for super-resolution microscopy is Advanced Light Microscopy (ALM) at SciLifeLab in Solna. ALM is a national research infrastructure resource that is open to scientists from around the country. “Super-resolution gives us unprecedented access to molecular mechanisms,” says ALM director Hjalmar Brismar, whose research group at the Department of Women’s and Children’s Health uses the technique. “We don’t only see the presence of a protein, but also where it is and how it moves.” The earliest adopters of the new tool have been neuroscientists and microbiologists.   Text: Anders Nilsson   View a news clip from SVT on the Nobel-winning discovery. (In Swedish.)  

Secretagogin triggers stress process in the brain

Thu, 27/11/2014 - 12:12
Researchers at Karolinska Institutet and MedUni Vienna in Austria have identified a new molecular mechanism to regulate stress. In a study published in the EMBO Journal, they show that the protein secretagogin plays an important role as a trigger in the release of the stress hormone CRH, which only then enables stress processes in the brain to be transmitted to the pituitary gland and onwards to the body. "If, however, the presence of secretagogin, a calcium-binding protein, is suppressed, then the Corticotropin Releasing Hormone, CRH, might not be released in the hypothalamus of the brain thus preventing the triggering of hormonal responses to stress in the body," says Tibor Harkany, a Professor of Neurobiology at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, and affiliated to the MedUni Vienna. The hypothalamus requires the assistance of CRH to stimulate the production and release of the hormone ACTH from cells in the pituitary gland into the blood stream. Thus, ACTH reaches the adrenal cortex and once there stimulates the production and release of further hormones, including the vital stress hormone cortisol. Upon stress, the hypothalamus responds by releasing CRH and thus produces the critical signal orchestrating also ACTH and cortisol secretion. However, if this cycle is interrupted, it is not possible for acute, and even chronic, stress to arise. Extended understanding Secretagogin was discovered 15 years ago by researchers at the MedUni Vienna, in connection with research on the pancreas. The researchers behind the current study now hope that their findings will provide an extended understanding of how hormonal responses to stress are generated. "This could result in a further development, where secretagogin is deployed as a tool to treat stress, perhaps in people suffering from mental illness such as depression, burn out or posttraumatic stress disorder, but also in cases of chronic stress brought on by pain”, says Tomas Hökfelt, MD, Senior Professor at the Department of Neuroscience, Karolinska Institutet. The study has been funded by the Swedish Research Council, The Swedish Brain Foundation, Petrus and Augusta Hedlund’s Foundation, Novo Nordisk Foundation, Karolinska Institutet, MedUni Vienna, the French National Research Agency, the European Commission, and the Wellcome Trust. Learn more in a press release from MedUni Vienna Publication A secretagogin locus of the mammalian hypothalamus controls stress hormone release Roman A Romanov, Alán Alpár, Ming-Dong Zhang, Amit Zeisel, André Calas, Marc Landry, Matthew Fuszard, Sally L Shirran, Robert Schnell, Árpád Dobolyi, Márk Oláh, Lauren Spence, Jan Mulder, Henrik Martens, Miklós Palkovits, Mathias Uhlén, Harald H Sitte, Catherine H Botting, Ludwig Wagner, Sten Linnarsson, Tomas Hökfelt & Tibor Harkany EMBO Journal, online first 27th November 2014, doi: 10.15252/embj.201488977

Professor Bob Harris – with an award and a sword

Thu, 27/11/2014 - 11:11
Getting the perfect hit on an opponent with a bamboo sword has much in common with medical research – at least if you ask Professor Bob Harris, who has been a competitor and instructor in the Japanese martial art of kendo for many years. One of this year’s two recipients of the KI pedagogy prize, he is the first to receive it for his contributions to doctoral education. “When doing kendo, you have to study your opponent during combat and look for weaknesses. It’s the same with research. It’s all about probing your way ahead and constantly striving to do things better.” His willingness to develop has also driven his passion for doctoral education. On being one of the two winners of this year’s pedagogy prize at KI along with teacher and researcher Lars Henningsohn at Clintec, he was acclaimed for having “been a driving force behind bringing an educational perspective into doctoral education.” “I’m happiest for the sake of doctoral education, and that the prize shows that the educational side of things is important there,” he says. His box of pedagogical tricks and activities contains webinars, lectures and seminars that students can stream from the net. He was also an early user of audience response systems, which enable his students to answer a question by pressing buttons and give immediate feedback on the compiled results. Robert Harris, or Bob as everyone calls him, is an advocate of interactivity in teaching and hopes to make that kind of technology more accessible, as he feels it is woefully underused at present. However, it is, he says, his commitment to changing views on doctoral education that won him the prize. “I’m fairly headstrong and not afraid of conflict,” he says. “I see myself as innovative, in terms of both research and doctoral education, and have high expectations, as I want to see wholesale improvements.” Bob Harris feels that there has been far too much emphasis on the results of the students’ research, and that the Swedish word for doctoral education, forskarutbildning (literally “researcher education”), is itself a problem. “Is it research or is it education? Many people think that research is what you do in the lab and education is what you do when you go away on a course. We want to move away from the idea that they’re two separate things.” When a doctoral student defends his or her thesis, it is up to the examination board to judge if he or she has attained the relevant intended learning outcomes. In recent years, the Board of Doctoral Education, on which Bob Harris sits, has been trying to raise awareness of these objectives amongst the students and their supervisors. By checking a student’s progress along the way, a supervisor, and the student, will both be able to judge if the objectives have been achieved and if a doctor’s hat is within reach. “Now, seven years on, we can see that the intended learning outcomes are an increasingly common feature of a defence,” says Bob Harris. “Doctoral education is about the training as well, not just the results presented in the published articles.” Doctoral education is a special kind of education, since it revolves so much around the collaboration of student and supervisor. The environments in which students work can be very different, and this depends in large part on their supervisors. And as for what makes a good supervisor, Bob Harris’s answer is simple: “They have time, that’s the main thing. The time and interest to see someone grow. And in return you get back some solid research.” He has attended many supervisor courses over the years, and admits that it can be something of a challenge for teachers who hold the same course year in year out to remain inspired when the same topics crop up again and again. “The secret is to see every group as a fresh opportunity. Each group is different and you have to be flexible enough to be able to adapt to them. So even if the subject’s the same, the way you teach it is different every time, and that’s what makes it enjoyable.” Back to kendo. Whether he’s teaching kendo or supervising doctoral students, there’s one thing that matters to Bob Harris, and that’s that each individual develops according to his or her abilities. “If all I can do is teach the stuff I know myself, I’d be a pretty rubbish teacher. I want them to be better researchers and better supervisors than I am. I’m happy to get whacked by my kendo students. I’m a tough trainer and a tough director of studies, because I expect a great deal from my students. But I’m a nice person too.”   Text: Karin Söderlund Leifler Photo: Gustav Mårtensson

Two studies identify pre-cancerous state in the blood

Thu, 27/11/2014 - 11:11
Researchers from Karolinska Institutet together with American colleagues have uncovered an easily detectable, “pre-malignant” state in the blood that significantly increases the likelihood to develop blood cancer. The discovery, which was made independently by two research teams, opens new avenues for research aimed at early detection and prevention of blood cancer. The findings are being published in the New England Journal of Medicine. Most research on blood cancer to date has focused on studying the genomes of advanced cancers, to identify the genes that are mutated in various cancer types. These two new studies instead looked at somatic mutations – mutations that cells acquire over time as they replicate and regenerate within the body – in DNA samples collected from the blood of individuals not known to have cancer or blood disorders.  Taking two very different approaches, the teams found that a surprising percentage of those sampled had acquired a subset – some but not all – of the somatic mutations that are present in blood cancers. These individuals were more than ten times more likely to go on to develop blood cancer in subsequent years than those in whom such mutations were not detected. The pre-malignant state identified by the studies becomes more common with age, and appears with in more than 10% of those over the age of 70. Carriers of the mutations are at an overall 5% risk of developing some form of blood cancer within five years. Limited clinical use Pre-malignant stage can be detected simply by sequencing DNA from blood. However, researchers point out that the findings at the moment are of limited clinical use at the moment, since there are no working therapies for cancer mutations in healthy people. The two studies were headed from Broad Institute of MIT and Harvard, and Harvard Medical School in Boston, USA. The work with collecting and analyzing data at Karolinska Institutet was led by Christina Hultman, a Professor at the Department of Medical Epidemiology and Biostatistics, in collaboration with Dr. Anna Kähler, Dr. Johan Lindberg, and Professor Henrik Grönberg. Funding bodies has been the Stanley Foundation, the National Institute of Health, the Swedish Research Council, the Swedish Cancer Society, StratCan and Strat Neuro at Karolinska Institutet, among others. Learn more in a press release from Broad Institute Publications ‘Age-related clonal hematopoiesis associated with adverse outcomes’, Jaiswal, S et al., New England Journal of Medicine, Online First November 26, 2014. DOI: 10.1056/NEJMoa1408617 ‘Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence’, Genovese, G et al., New England Journal of Medicine, Online First November 26, 2014, DOI: 10.1056/NEJMoa1409405. 

2014 Nobel prize winners: “It was a wonderful moment“

Thu, 27/11/2014 - 11:11
Fantastic! A shock! One of the best things that’s ever happened to me! When John O’Keefe, May-Britt Moser and Edvard Moser are asked how it felt to win this year’s Nobel Prize in Physiology or Medicine, they all gush with joy and surprise. “It’s the most prestigious award a scientist can receive,” says John O’Keefe, professor of cognitive neuroscience at University College London, UK, who discovered the positioning cells that earned him the 2014 Nobel Prize in Physiology or Medicine. By registering neuronal activity in the brains of free-roaming rats, he found that certain cells of the hippocampus were activated when the rat was in a particular location. “It was a wonderful moment when I saw the correlation,” he says. “A vast amount of literature, written over thousands of years, has tried to come to grips with the problem of understanding the connection between the space we experience and the physical world.” John O’Keefe was one of the first scientists to register the activity of individual nerve cells in free-roaming animals, and says that new techniques that reveal new things are behind many important scientific breakthroughs, and that he would like to see more such research in the future. “We must get better at giving researchers, particularly junior ones, the freedom to explore using new techniques and new ideas, and sometimes to make mistakes without feeling the pressure of having to publish articles in respected journals,” he says. He adds that breakthroughs can also only occur when the scientist understands that he or she has discovered something important. His fellow laureates, May-Britt and Edvard Moser, both professors of neuroscience at Norway’s Teknisk‐Naturvitenskapelige Universitet in Trondheim, agree: Focusing is crucial “John O’Keefe and we made our discoveries in similar ways: we saw something that we hadn’t been expecting, and continued to study it, and in both cases it was a combination of luck and a readiness to handle the unexpected,” says Professor Edvard Moser, adding that courage, patience, creativity and the ability to focus on the right questions are also crucial to scientific success. He and May-Britt Moser discovered the so-called grid cells in the entorhinal cortex, a part of the brain close to the hippocampus, after observing that these cells not only were activated when a rat passed by a certain point in its environment but also that they gave off a signal when it was at nearby locations. “At first we suspected a regular pattern, but when the rats were allowed to roam over a larger area, a hexagonal grid emerged,” says Professor May-Britt Moser. “A special neuron was activated when a rat passed one of the points of a hexagon. What’s fascinating is that nothing in the rat’s environment had this shape. The pattern is one of a very few known to be created by the brain itself.” The grid cells, the place cells and other cells that indicate head orientation, speed of movement and nearby obstacles are part of a system that probably exists in all mammals and that functions as an internal GPS. The system also plays an important part in how we create memories. John O’Keefe first met May-Britt and Edvard Moser when they were doctoral students at Oslo University in Norway. “I could tell right away that these two would become stars in the world of science, and was happy when they then asked to come to my lab to learn our techniques,” he says. “They turned out to be two of fastest learners I’ve ever supervised. Today, we’re not just colleagues interested in the same part of the brain, but very good friends too.”  O'Keefe a mentor May-Britt and Edvard Moser describe John O’Keefe as a mentor, who taught them, amongst many other things, about the importance of maintaining a high level of quality in their research to ensure that it is reliable and replicable. “Excellent research must be excellent every step of the way, and this takes efficient research teams and healthy, happy laboratory animals,” says May-Britt Moser. When asked how their research will benefit humankind, all three laureates mention Alzheimer’s disease. “The disease onsets with lesions in the part of the brain where these cells are fond, and some of the first symptoms are an impaired positional sense and an impaired memory,” says Edvard Moser. “Since the disease develops very slowly, it might be possible to stop it if we can find out what’s going wrong. But first, we have to understand how the normal brain works.” He and May-Britt Moser are now focusing on finding out how all cell types in the advanced positional system interact, and on trying to understand how the grid pattern arises. “The brain is complex but conservative, and often uses the same trick again and again,” says Edvard Moser. “Maybe we can learn something about completely different cognitive functions as well.” They are also, he continues, both interested in understanding how the positional system integrates with motor cells. Lot to learn from KI “I should think there’s a lot here to learn from Karolinska Institutet, where a lot of research is going on about how the brain controls movement and takes us from A to B.” John O’Keefe plans to continue his work on the hippocampus, but has also started to take an interest in the amygdala, part of the brain that belongs to the limbic system. “I’m driven in my research by curiosity, and go to the lab every day in the hope of finding something new and, ideally, important,” he says. “As I mentioned before, new technologies can pave the way for new discoveries, and right now we’re planning to develop methods for registering electric signals from thousands of nerve cells at once.” All three agree that the Nobel Prize is a hallmark of quality. While May-Britt Moser hopes that the prize will also boost the recruitment of top researchers to her and her husband’s groups, John O’Keefe is more sceptical about the effect. “Maybe it’ll be easier to get research grants, but then again it could also be harder,” he says with a laugh.   Text: Lisa Reimegård   John O’Keefe was born in 1939 in New York City, USA, and is both a US and British citizen. After earning his PhD in physiological psychology in 1967 at McGill University in Montreal, Canada, he moved to England to research at University College London, where he was appointed professor of cognitive neuroscience in 1987. John O’Keefe is currently head of the Sainsbury Wellcome Centre for Neural Circuits and Behaviour at the same university. May‐Britt and Edvard Moser were both born in Norway, she in 1963 and he in 1962. They studied psychology at Oslo University and took their PhDs in neurophysiology in 1995, after which they did their postdoc research at the University of Edinburgh and with John O’Keefe at University College London. In 1996 they returned to Norway and established a research laboratory at the Teknisk‐Naturvitenskapelige Universitet in Trondheim. Edvard Moser was made professor of neuroscience in 1998, and May‐Britt Moser in 2000. May-Britt Moser is currently director of the university’s Centre for Neural Computation and Edvard Moser of the Kavli Institute for Systems Neuroscience in Trondheim. Nobel Lectures in Physiology or Medicine 2014, December 7 at Karolinska Institutet

Students eat pizza with Vice-Chancellor

Wed, 26/11/2014 - 09:09
The mood was free, as were the pizzas. KI students assembled last Monday to ply Vice-Chancellor Anders Hamsten with questions. “It’s easy for a vice-chancellor to become invisible, so every opportunity to come and talk to the students is good,” said Professor Hamsten. The students were enticed into the Huddinge campus university library with free pizza, and as they munched their capricciosa and veggie slices, they listened to the Vice-Chancellor answer questions about KI’s new strategy, Strategy 2018. “I came for the combination of a free lunch and an interesting Q&A session,” said medical student Magdalena Lublin. The questions concerned contact with business, a smoking ban, a gym, computer support and much more besides. When it came to IT support, Professor Hamsten didn’t mince his words: “KI slaps its brow, you could say. This is a huge problem right now. Our own IT platform is sub-standard and security is poor. But we’re aware of this and are working on it. But then the county council’s own network must also work properly, but that’s up to them, not us.” Medical student Michael Plattén raised the paradox that while it’s KI’s mission to promote health, there’s no smoking ban outdoors or a gym. “We really should lead by example, and show that we take our own health seriously too,” he said. There’ll be a gym, but not for another two or three years, promised the Vice-Chancellor, who also said that it would be impossible to ban smoking outdoors. Biomedicine Master’s student Peter Solsjö, the moderator for the afternoon, wanted to see closer contacts with the business community – ideally some kind of corporate fair – to give KI students a better view of the entire labour market. “Yes, that’s a good idea,” agreed Professor Hamsten. “In fact, a committee has been set up with the pro-Vice-Chancellor to look at things like how doctors and engineers in Huddinge can come together to learn from each other. Maybe we need some kind of common student union building.” Afterwards, a dozen or so people remained behind to ask further questions.   The free pizza and Q&A session will be repeated on the Solna campus on 3 December, this time exclusively in English.   Photo: Erik Cronberg

Gut microbiota influences blood-brain barrier permeability

Thu, 20/11/2014 - 08:08
A new study in mice, conducted by researchers at Sweden’s Karolinska Institutet together with colleagues in Singapore and the United States, shows that our natural gut-residing microbes can influence the integrity of the blood-brain barrier, which protects the brain from harmful substances in the blood. According to the authors, the findings provide experimental evidence that our indigenous microbes contribute to the mechanism that closes the blood-brain barrier before birth. The results also support previous observations that gut microbiota can impact brain development and function. The blood-brain barrier is a highly selective barrier that prevents unwanted molecules and cells from entering the brain from the bloodstream. In the current study, being published in the journal Science Translational Medicine, the international interdisciplinary research team demonstrates that the transport of molecules across the blood-brain barrier can be modulated by gut microbes – which therefore play an important role in the protection of the brain.  The investigators reached this conclusion by comparing the integrity and development of the blood-brain barrier between two groups of mice: the first group was raised in an environment where they were exposed to normal bacteria, and the second (called germ-free mice) was kept in a sterile environment without any bacteria. “We showed that the presence of the maternal gut microbiota during late pregnancy blocked the passage of labeled antibodies from the circulation into the brain parenchyma of the growing fetus”, says first author Dr. Viorica Braniste at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet. ”In contrast, in age-matched fetuses from germ-free mothers, these labeled antibodies easily crossed the blood-brain barrier and was detected within the brain parenchyma.” Maintained into adulthood The team also showed that the increased ‘leakiness’ of the blood-brain barrier, observed in germ-free mice from early life, was maintained into adulthood. Interestingly, this ‘leakiness’ could be abrogated if the mice were exposed to fecal transplantation of normal gut microbes. The precise molecular mechanisms remain to be identified. However, the team was able to show that so-called tight junction proteins, which are known to be important for the blood-brain barrier permeability, did undergo structural changes and had altered levels of expression in the absence of bacteria. According to the researchers, the findings provide experimental evidence that alterations of our indigenous microbiota may have far-reaching consequences for the blood-brain barrier function throughout life. “These findings further underscore the importance of the maternal microbes during early life and that our bacteria are an integrated component of our body physiology”, says Professor Sven Pettersson, the principal investigator at the Department of Microbiology, Tumor and Cell Biology. “Given that the microbiome composition and diversity change over time, it is tempting to speculate that the blood-brain barrier integrity also may fluctuate depending on the microbiome. This knowledge may be used to develop new ways for opening the blood-brain-barrier to increase the efficacy of the brain cancer drugs and for the design of treatment regimes that strengthens the integrity of the blood-brain barrier”. The study was funded with grants from the Swedish Research Council, the Swedish Brain Foundation, the research consortium TORNADO within the EU’s Seventh Framework Programme, Merieux Foundation, Wenner-Gren Foundation, Singapore Millenium foundation, and the Nanyang Technological University in Singapore. Professor Sven Pettersson is also affiliated to the Lee Kong Chian School of Medicine, The National Cancer Centre in Singapore and the Singapore Centre on Environmental Life Sciences Engineering at the Nanyang Technological University. View a press release about these findings Publication The gut microbiota influences the blood brain barrier permeability in mice Viorica Braniste, Maha Al-Asmakh, Czeslawa Kowa, Farhana Anuar, Afrouz Abbaspour, Miklos Toth, Agata Korecka, Nadja Bakocevic, Ng Lai Guan, Parag Kundu, Balazs Gulyas, Christer Halldin, Kjell Hultenby, Harriet Nilsson, Hans Hebert, Bruce T. Volpe, Betty Diamond, Sven Pettersson Science Translational Medicine, online 19th November 2014,  DOI: 10.1126/scitranslmed.3009759

Medium amount of physical activity can lower risk of Parkinson’s

Wed, 19/11/2014 - 08:08
A new study by researchers at Karolinska Institutet shows that a medium amount of physical activity in daily life lowers the risk of Parkinson’s disease, compared to a very low level physical activity. The study, which is being published online in the journal Brain, followed 43,368 individuals in Sweden during a 12 year period. The research team used the Swedish National March Cohort to analyse comprehensive information on physical activity of all kinds. They assessed household and commuting activity, occupational activity, leisure time exercise, and total daily physical activity according to data provided by 27,863 females and 15,505 males, as part of an extensive questionnaire. For the purpose of this study, physical activity was quantified into metabolic equivalent (MET) hours per day, based on estimated oxygen consumption associated with those activities. All participants were free of Parkinson’s disease in October 1997, the start of the follow-up period. Study participants were followed from this baseline until date of diagnosis with Parkinson’s disease, date of death, date of emigration, or the end of the follow-up period in December 2010, whichever came first. In that time 286 cases of Parkinson’s disease were identified. More than six hours per week In the study’s multivariable-adjusted model, compared with participants who spent less than two hours per week on household and commuting activity, those who spent more than six hours per week on the same types of activities had a 43% lower risk of developing Parkinson’s disease. Compared with a low level of total physical activity, a medium level of total physical activity (a mean of 39.1 MET hours per day) was associated with a 45% lower Parkinson’s disease risk in males. In women the results were not as consistent, but the protective effect of physical activity in this group was supported when researchers summarized all available evidence from published prospective cohort studies. Leisure time exercise was not associated with Parkinson’s disease risk when analysed alone. “One of many strengths of this study is that all information on physical activity and daily energy output was assessed before the disease occurrence, making recall bias and reverse causation less likely. The results show that a few hours spent at the gym do not have the protective effect that one would wish, but it is the physical activity in daily life that is of greater importance”, says Karin Wirdefeldt, researcher at Karolinska Institutet’s Department of Medical Epidemiology and Biostatistics, and Department of  Clinical Neuroscience, who headed the study.“ First study-author is Fei Yang, doctoral student at the Department of Medical Epidemiology and Biostatistics. The work was funded by the Swedish Research Council, the Swedish Cancer Association, ICA Sweden, Ericsson, Karolinska Institutet and the Stockholm County Council. Find a press release from Oxford University Press about this study Publication Physical activity and risk of Parkinson’s disease in the Swedish National March Cohort Fei Yang, Ylva Trolle Lagerros, Rino Bellocco, Hans-Olov Adami, Fang Fang, Nancy L. Pedersen, Karin Wirdefeldt Brain, online 19th 2014, DOI: 10.1093/brain/awu323

Two researchers share the Karolinska Stroke Award

Tue, 18/11/2014 - 10:10
Professor Vladimir Hachinski, London, Ontario, and Professor Bo Norrving, Lund is jointly awarded the Karolinska Stroke Award for Excellence in Stroke Research 2014. Professors Hachinski and Norrving received the award from Vice Chancellor Anders Hamsten, Karolinska Institutet, in connection with the ongoing ESO Karolinska Stroke Update meeting in Stockholm. The award is 100,000 Swedish kronor and is shared between the awardees, for “their leading role in clinical stroke research, in particular the understanding of stroke syndromes, pathophysiological mechanisms of stroke and cerebrovascular diseases, and the organisation of stroke services.” Among professor Hachinski most important discoveries are the key role of the insula of the brain for sudden death and, together with other researchers, the ischaemia-amyloid – inflammation link between Alzheimer disease and stroke, paving the way for novel therapeutic approaches. Professor Norrving was corresponding author of the Swedish Aspirin Low Dose Trial (SALT), a landmark publication in the Lancet in 1991, later included in Vintage Papers from Lancet of the most important papers from 1823 to 2005. His main research activities have been focused on stroke epidemiology, stroke syndromes, small vessel disease, ultrasound, neuroimaging, clinical genetics, clinical trials and organisation of stroke services. Read more avout Stroke Update 2014.

Young vessels rejuvenate aged insulin-producing beta cells

Tue, 18/11/2014 - 08:08
A recent study published in the journal PNAS shows that young capillary vessels rejuvenate aged pancreatic islets. The finding challenges prevailing views on the causes of age-dependent impaired glucose balance regulation, a condition that often develops into diabetes type 2. The international research team behind the study now suggests that targeting inflammation and fibrosis in the small blood vessels of the pancreatic islets may offer a new way of treatment for age-dependent dysregulation of blood glucose levels. “This is an unexpected but highly important finding, which we expect will have a significant impact on diabetes research in the future. The results indicate that beta cell function does not decline with age, and instead suggest that islet function is threatened by an age-dependent impairment of vessels that support them with oxygen and nutrients”, says Per-Olof Berggren at the Rolf Luft Research Center for Diabetes and Endocrinology at Karolinska Institutet, who led the study together with Alejandro Caicedo at University of Miami Miller School of Medicine and Hong Gil Nam at DGIST in Republic of Korea. Beta cells are located in the pancreatic islets and secrete the hormone insulin, that play a key role in regulating blood glucose levels. Ageing may lead to a progressive decline in glucose regulation which may contribute to diabetes development. Generally, it has been assumed that this is due to reduced capacity of the beta cell to secrete insulin or multiply. “In the study we challenged the view that the age-dependent impairment in glucose homeostasis is solely due to intrinsic, dysfunction of islet cells, and hypothesized that it is instead affected by systemic aging factors”,  says first author Joana Almaça at the Diabetes Research Institute, University of Miami.  Replacing the islet vasculature  In marked contrast to the widely held notion that the insulin-producing pancreatic beta cell loses function with wear and tear, the researchers now show that mouse and human beta cells are fully functional at advanced age. When replacing the islet vasculature in aged islet grafts with young capillaries, the investigators found that the islets were rejuvenated and glucose homeostasis fully restored.  “While expanding beta cell mass may still be desirable for future diabetes therapy, improving the local environment of the otherwise healthy aged beta cell could prevent age-associated deterioration in glucose homeostasis and thereby promote healthy ageing, which is conceptually novel and highly exciting”, says Per-Olof Berggren. The work conducted at Karolinska Institutet was mainly funded by the Swedish Research Council, the Swedish Diabetes Association, the Novo Nordisk Foundation, the Knut and Alice Wallenberg Foundation, the Family Erling-Persson Foundation and European Research Council. View a press release about these findings Publication Young Capillary Vessels Rejuvenate Aged Pancreatic Islets Joana Almaça, Judith Molina, Rafael Arrojo, Rafael Arrojo e Drigo, Midhat H. Abdulreda, Won Bae Jeon, Per-Olof Berggren, Alejandro Caicedo, and Hong Gil Nam PNAS, Online Early Edition the week of Nov 17-Nov 21, 2014, doi: 10.1073/pnas.1414053111

Hats on for Karolinska Institutet’s new doctors

Mon, 17/11/2014 - 13:13
Karolinska Institutet’s new doctors of medicine, all of whom held their public defences in the spring, officially received their degrees last Friday (14 November). Tribute was also paid at the ceremony to the year’s jubilee doctors and KI awarded its Gold Medal for the first time since the bicentenary in 2010 – to university chancellor Harriet Wallberg, KI’s former president (vice-chancellor). In the November gloom of Stockholm’s City Hall, lit only by candles that spread a warm light along the balustrade, the spotlight trained on the new doctors seemed even stronger. All 117 new doctors received their doctoral hat and diploma from Dean of Doctoral Education Anders Gustafsson, as cannon fired a salute from the City Hall waterfront to mark the end of up-to five year’s work as doctoral students and its culminating in academic theses.  “It’s all about hard work and trying to solve problems,” said Professor Gustafsson, who quoted Nobel literature laureate Samuel Beckett’s words on never giving up: “Try again. Fail again. Fail better.” Fourteen jubilee doctors, who received their degrees from Karolinska Institutet 50 years ago, were also celebrated, amongst them anti-doping specialist Professor Arne Ljungqvist, to whom the government recently decided to award a medal in recognition of his work. Vice-Chancellor Anders Hamsten expressed his sincere thanks to the jubilee doctors for their contributions to science and for having prepared the way for new generations. Professor Hamsten also awarded Karolinska Institutet’s Gold Medal to Professor Harriet Wallberg for her “exceptional contributions” to the university. Of particular note in this regard was the fundraising campaign that she initiated during her university presidency (2004–2012) and that generated proceeds of a billion kronor for research and for Aula Medica, which opened in 2013. Photo credit: Ulf Sirborn and Stefan Zimmerman

Childhood central nervous system cancer affects identity in adulthood

Mon, 17/11/2014 - 08:08
Patients who have been treated for cancer of the central nervous system (brain tumours) in childhood or adolescence can show affected self-perception and self-identity in adulthood. This is concluded in a recent study from Karolinska Institutet in Sweden which is being published in the scientific journal Neuro-Oncology. Undesirable persistent late-effects affect a considerable number of adults who survived childhood central nervous system (CNS) cancer. The study followed 700 adult survivors diagnosed 1992-2001 with a childhood CNS tumour. The study group covered all adult brain tumour survivors in Sweden at the time of start of study. Patients were compared with a control group selected from the general population. In addition to health and function, researchers also studied how the illness, the brain tumour treatment and the aftermath affected patients’ psychological identity, i.e. their self-perception and self-esteem in contexts where these play a significant role, such as family, friends, work and sports. Physical body image and an overall self-esteem index were also covered. In addition to specific medical and treatment information collected from medical registers, late-effects status and self-perception factors were addressed using a standardised self-report questionnaire. The results demonstrate that the late-effects of CNS cancer of childhood are not restricted to health and physical and neuro-psychological function. The illness experience as a whole, with the increased risk for tumour/treatment-related damage intrudes upon on self-perception and contribute to shaping of psychological identity. Compared with the general  population, survivors had less favourable outcomes in several of studied aspects. Negative self-perception A negative instead of positive self-perception was more common among survivors. In the contexts of work and friends, for example, 22%and 30% of patients had a negative self-perception compared with 8% and 17% in the control group. In context of family, though, self-perception parcelled that of the general population. Earlier radiation treatment towards the brain and permanent physical scars increased the risk for an adverse effect on self-perception in adulthood. “The study confirms that these patients are in the risk zone for a wide spectrum of late-effects”, says Krister K. Boman, principal investigator at the Department of Women’s and Children’s Heath at Karolinska Institutet. In addition to health-related, neuro-cognitive and function problems they also engage personality factors linked to identity, mental health and psychological well-being. The results bear witness of the width of the psychological consequence of brain tumour illness in childhood, and of the necessity of adequate support, and of psychosocial rehabilitation resources. These findings allow for specifying the need for early and continued preventative measures for these patients.” Researchers point to that the findings verify the importance of intensified preventative measures in health care, and a follow-up plan extended into adulthood that meets the specific needs of adult patients who survived paediatric brain cancer. In addition to measures against earlier known problems, medical health care has to attend to that CNS diseases and treatment intrudes upon long-term personality development. The study was conducted with funding from Swedish Childhood Cancer Foundation and Karolinska Institutet research grants. View a press release about the study Publication Altered self-perception in adult survivors treated for a CNS tumor in childhood or adolescence: population-based outcomes compared with the general population Hörnquist L, Rickardsson J, Lannering B, Gustafsson G, Boman KK Neuro-Oncology, early online 20 October  2014; doi:10.1093/neuonc/nou289

Beta blockers could benefit patients with HFPEF

Sun, 16/11/2014 - 17:17
A novel registry study from Karolinska Institutet in Sweden suggests that beta blockers may benefit also patients suffering from a relatively unknown form of heart failure called HFPEF, which today lacks well-established treatment. HFPEF involves an impaired ability of the heart to fill with blood, and affects nearly 2 per cent of the population. These new findings are being published in the scientific periodical JAMA. Heart failure was for a long time defined as reduced ability to contract the heart and pump oxygenated blood out to the rest of the body. This condition is often caused by long-standing high blood pressure or a previous heart attack. Men are affected more often than women, and there are several treatments improving symptoms and survival. However, in recent years it has become clear that a new type of heart failure is equally common and serious. This type of heart failure, called HFPEF or heart failure with preserved ejection fraction, involves a reduced ability in the heart to relax and fill with blood. HFPEF is more common at old age and affects women more often than men. Until recently, there was no treatment against this disorder. In the current study, a Swedish team comprising researchers from Karolinska Institutet, Linköping University, Stockholm South General Hospital, Danderyd Hospital and Karolinska University Hospital analysed data from 42,000 patients from the nation-wide Swedish Heart Failure Registry. According to the findings, patients with HFPEF who were treated with beta blockers had better survival than untreated patients. The difference persisted after adjustment for a large number of other factors, such as patient age, general health, socioeconomic and other factors, and the final decrease in mortality was 7 per cent in the group treated with beta blockers. Damage the heart in the long-term In heart failure, stress hormones such as adrenaline are secreted and damage the heart in the long-term. Beta blockers protects against this damaging effect. In randomized trials in patients with reduced ability to contract the heart, beta blockers have been shown to reduce mortality. However, this is the first comprehensive study regarding the effect of beta blockers in patients with HFPEF. In a previous study, the Swedish team also reported that HFPEF patients could benefit from other similar heart drugs, such as ACE-inhibitors and angiotensin receptor blockers. Researchers now plan to proceed with randomized clinical trials. "This study was large and rigorous, but still cannot prove that beta blockers are beneficial in HFPEF”, says Principal Investigator Lars H. Lund, Docent at Karolinska Institutet. “However, it provides a rationale for performing large-scale randomized trials with this inexpensive category of drugs, which we now plan to go through with. Sweden has unique capabilities to implement such randomized studies in the context of the major Swedish quality registries.” The work was financed by the Swedish Research Council, The Swedish Heart-Lung Foundation, the Stockholm County Council and the Swedish Association of Local Authorities and Regions. View a press release about this study Publication Association between Use of Beta-Blockers and Mortality in Patients with Heart Failure and Preserved Ejection Fraction Lars H. Lund, Lina Benson, Ulf Dahlström, Magnus Edner, Leif Friberg JAMA. 2014;312(19):2008-2018. doi:10.1001/jama.2014.15241

New immunological findings provide possible therapy for cardiovascular disease

Fri, 14/11/2014 - 08:08
A new immunological mechanism in atherosclerosis and cardiovascular disease has been presented in a study from Karolinska Institutet in Sweden. The study is being published in the journal Arteriosclerosis, Thrombosis, and Vascular Biology, and also indicates a possible treatment method for these diseases. Atherosclerosis is an inflammatory process where lipidsin the form of LDL cholesterol (‘bad cholesterol’) are stored in the artery walls. The activation of the immune system in the form of T-cells, among others, plays a vital role, particularly for rupturing the atherosclerotic plaques which, the primary cause of myocardial infarction and stroke. LDL is only taken up in the artery wall after modification, a process where oxidation is one probable underlying cause. Enzymes in the artery walls can also modify LDL making it inflammatory. Most basic scientific studies in the field are based mouse models with genetic changes as mice cannot develop arteriosclerosis or cardiovascular disease. Plaque cells and blood Together with his research team, Dr. Johan Frostegård, Professor of Medicine at the Institute of Environmental Medicine at Karolinska Institutet, has studied inflammatory and immune defence reactions in atherosclerosis and cardiovascular disease using plaque cells and blood from patients with cardiovascular disease. The researchers have observed that the lipids (phospholipids) in modified LDL appear to be one of the primary causes. The research team has shown that LDL that is modified by enzymes in the artery walls can activate dendritic cells, which in turn play a key role in activating the T-cells. Non-modified, regular LDL on the other hand had no effect on these cells in the study. The research also indicates the possible existence of a mechanism, namely that stress proteins (also called heat shock proteins) are expressed, which is decisive when modified LDL activates the dendritic cells and T-cells. The study shows that a plasma protein Annexin A5 decreases inflammation and modulates immune reactions to modified LDL, which creates a protective effect. “Studying the inflammatory process and immune reactions directly in cells from people with cardiovascular disease is a unique opportunity to discover the causes and new mechanisms behind the disease's progression. We have shown that modified LDL can play a key role and that stress proteins have a major significance to immune defence reaction,” says Johan Frostegård. Fighting inflammatory process With the new results, Dr. Frostegård and his team hope to find a strategy for fighting the inflammatory process. “We have shown that Annexin 5 is a possible new therapy for fighting inflammation and supports the immune defence system is a positive way. We hope to develop this protein into a new type of anti-inflammatory treatment for atherosclerotic disease,” he says. The study was funded with grants from the Torsten Söderberg Foundation, Vinnova, the EU, and RMR. Johan Frostegård is also specialist consultant at the Emergency Clinic at Karolinska University Hospital, Huddinge in Stockholm County. The researchers and their European partners have applied for a larger EU grant to fund the continuing basic research studies and also treatment studies on patients with cardiovascular disease, which is backed by several patents. View a press release about the findings Publication Induction of dendritic cell-mediated T cell activation by modified but not native LDL in humans and inhibition by Annexin A5: involvement of heat shock proteins Liu A, Ming J, Fiskesund R, Ninio E, Karabina S, Bergmark C, Frostegård AG, Frostegård J Arteriosclerosis, Thrombosis, and Vascular Biology, published online before print November 13, 2014,doi: 10.1161/ATVBAHA.114.304342