Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

KI News

Updated: 10 min 26 sec ago

Green leafy vegetables may prevent liver steatosis

Mon, 17/12/2018 - 21:00
A larger portion of green leafy vegetables in the diet may reduce the risk of developing liver steatosis, or fatty liver. In a study published in PNAS researchers from Karolinska Institutet in Sweden show how a larger intake of inorganic nitrate, which occurs naturally in many types of vegetable, reduces accumulation of fat in the liver. There is currently no approved treatment for the disease, which can deteriorate into life-threatening conditions such as cirrhosis and liver cancer. Liver steatosis, or fatty liver, is a common liver disease that affects approximately 25 per cent of the population. The most important causes are overweight or high alcohol consumption and there is currently no medical treatment for the disease. Researchers at Karolinska Institutet have now shown how a greater intake of inorganic nitrate can prevent the accumulation of fat in the liver. “When we supplemented with dietary nitrate to mice fed with a high-fat and sugar Western diet, we noticed a significantly lower proportion of fat in the liver,” says Mattias Carlström, Associate Professor at the Department of Physiology and Pharmacology, Karolinska Institutet. Their results were confirmed by using two different cell culture studies in human liver cells. Apart from a lower risk of steatosis, the researchers also observed reduction of blood pressure and improved insulin/glucose homeostasis in mice with type 2 diabetes. The research group’s focus is the prevention of cardiovascular diseases and type 2 diabetes through dietary changes and by other means. Previous studies have shown that dietary nitrate from vegetables enhances the efficiency of the mitochondria, the cell’s power-plant, which can improve physical endurance. It has also been shown that a higher intake of fruit and vegetables has a beneficial effect on cardiovascular function and on diabetes. “We think that these diseases are connected by similar mechanisms, where oxidative stress causes compromised nitric oxide signalling, which has a detrimental impact on cardiometabolic functions,” says Dr Carlström. “We now demonstrate an alternative way to produce nitric oxide, where more nitrate in our diet can be converted to nitric oxide and other bioactive nitrogen species in our body.” Even though many clinical studies have been done, there is still considerable debate about what properties of vegetable make them healthy. “No one has yet focused on nitrate, which we think is the key,” continues Dr Carlström. “We now want to conduct clinical studies to investigate the therapeutic value of nitrate supplementation to reduce the risk of liver steatosis. The results could lead to the development of new pharmacological and nutritional approaches.” While larger clinical studies are needed to confirm the role of nitrate, the researchers can still advise on eating more green leafy vegetables, such as regular lettuce or the more nitrate-rich spinach and rocket. “And it doesn’t take huge amounts to obtain the protective effects we have observed – only about 200 grams per day,” says Dr Carlström.“ Unfortunately, however, many people choose not to eat enough vegetables these days.” The study was financed by the Swedish Research Council, the Swedish Heart and Lung Foundation, Novo Nordisk, the European Research Council and Karolinska Institutet. Two of the authors, Jon O Lundberg and Eddie Weitzberg, are coinventors on patent applications related to the therapeutic use of inorganic nitrate. Magnus Ingelman-Sundberg is cofounder of the contract research organisation (CRO) HepaPredict AB. Publication “AMP-activated protein kinase activation and NADPH oxidase inhibition by inorganic nitrate and nitrite prevents liver steatosis”. Isabel Cordero-Herrera, Mikael Kozyra, Zhengbing Zhuge, Sarah McCann Haworth, Chiara Moretti, Maria Peleli, Mayara Caldeira-Diaz, Arghavan Jahandideh, Han Huirong, Josiane Cruz, Andrei Kleschyov, Marcelo Montenegro, Magnus Ingelman-Sundberg, Eddie Weitzberg, Jon O Lundberg and Mattias Carlström. PNAS, online 17 December 2018, doi: 10.1073/pnas.1809406115.

KI students won award for best environmental project

Wed, 12/12/2018 - 12:49
Students at Karolinska Institutet (KI) have, together with students from KTH and Konstfack, developed a method for cleaning wastewater from antibiotic and other drug residues before reaching the sea. The idea and prototype was presented in an international competition in synthetic biology, where the Stockholm team won the first prize in two categories. The Stockholm team, which is called iGEM Stockholm, participated in the annual competition in Boston, founded by MIT, in October. iGEM ​​Stockholm won gold and also became total winners in the “Best Environmental Project” and “Best integrated human practices” categories, which deals with how the project affects community needs and how to deal with aspects such as sustainability and ethics. iGEM ​​Stockholm focused on the Baltic Sea's problems with the release of antibiotics and drugs from wastewater. "We managed to show that laccase, an enzyme found naturally in yeast which breaks down wood, could break down antibiotics with well-prepared protocols and experiments. This, combined with our completed project where we went beyond the lab by integrating community and expert opinions and suggesting a product on the market, made us stand out from the rest of the teams in our track, says Els Alsema, a master student in the biomedicine program at KI. In the global scientific competition iGEM in synthetic biology, approximately 350 teams participated. The competition is being conducted during the summer with a final in Boston this fall. The student teams will solve any problem they formulate themselves, for example in therapy, diagnostics or the environment using molecular biology methods by applying their knowledge.

New method for studying ALS more effectively

Wed, 12/12/2018 - 07:00
The neurodegenerative disease ALS causes motor neuron death and paralysis. However, long before the cells die, they lose contact with the muscles as their axons atrophy. Researchers at Karolinska Institutet have now devised a new method that radically improves the ability to study axons and thus to better understand the pathological development of ALS. The method is described in the scientific journal Stem Cell Reports. All neurons have a fibre-like projection called an axon, and those of motor neurons can be extremely long – over a metre – as they have to stretch from the spinal cord to the muscles of the arms and legs. It is known that in ALS the motor neurons die “backwards” and lose functionality where the axon meets the muscle before gradually atrophying completely. By examining the presence of RNA in a cell, it is possible to discover which genes are switched on and off and thus the cell’s function and general condition. In long-axoned neurons, there is a buffer of RNA in the axon that enables them to quickly interact with their environment – e.g. muscle cells. Scientists are keenly interested in investigating the repertoir of RNAs in motor axons of healthy individuals and ALS patients to gain deeper insight into disease processes. However, this has proven to be very difficult as the amount of RNA in axons is minute. If just one single cell body gets into the axon study material, it will contaminate it with its own RNA, making it impossible to see what the axon’s RNA reservoir looks like. “We have now developed a greatly improved method for this called Axon-seq,” explains Eva Hedlund,  associate pofessor at the Department of Neuroscience, Karolinska Institutet. “It’s a relatively cheap, simple and highly sensitive method that we’ve described in detail in our study so that it can be used by other researchers interested in studying neuronal processes.” Examine motor neurons Her research group has used the method to examine motor neurons generated from mouse and human stem cells. Their results show that the axon’s reservoir of RNAs differs significantly from that of the cell body, which is a new discovery. The researchers also examined the transcriptome of ALS-diseased motor neurons and found that in neurons with the mutated version of the SOD1 gene that causes ALS, the axon’s RNA profile differed fromthat of healthy cells. “Many of the genes we found dysregulated in ALS are needed for the normal function of the axon and its contact with the muscle,” says Jik Nijssen, doctoral student and joint first-author of the study with Julio Aguila Benitez. “Many of these genes present possible targets for future therapies.” The study was financed by the Swedish Research Council, the EU Joint Programme – Neurodegenerative Disease Research (JPND), the Strategic Research Area in Neuroscience at Karolinska Institutet (StratNeuro), the Birgit Backmark endowment for ALS research at Karolinska Institutet in memory of Nils and Hans Backmark, the Åhlén Foundation, the Ulla-Carin Lindquist Foundation for ALS Research, the Magnus Bergvall Foundation, the Swedish Society for Medical Research and the Swedish Brain Fund. Publication Axon-seq decodes the motor axon transcriptome and its modulation in response to ALS  Jik Nijssen, Julio Aguila Benitez, Rein Hoogstraaten, Nigel Kee, Eva Hedlund Stem Cell Reports, online 11 December 2018, DOI: https://doi.org/10.1016/j.stemcr.2018.11.005.

Cured cancer patients in focus when Nobel Laureates lectured at KI

Tue, 11/12/2018 - 17:45
The Nobel Lectures held by the laureates of the 2018 Nobel Prize in Physiology or Medicine saw the Erling Persson Hall in Aula Medica at Karolinska Institutet filled to the brim. In addition to 1,000 audience members in the hall, people around the world were able to watch the live broadcast when James P. Allison and Tasuku Honjo talked about their research, the results of which have led to the ground-breaking immune checkpoint therapy for cancer treatment. The grey and drizzly December weather did not prevent expectant students and others from forming a queue that stretched down Solnavägen for a little over an hour before the Nobel Lectures in Physiology or Medicine began this year. Karolinska Institutet’s (KI) President Ole Petter Ottersen gave a welcoming speech and emphasised that tonight is a celebration of research that is about testing boundaries. He thanked the Laureates for their discoveries, after which Edvard Smith, KI Professor and member of the Nobel Committee, presented the Laureates in more depth with an introduction that provided both a personal and professional background. No biology without Darwin Smith spoke about James P. Allison, born in the United States in 1948, with an early interest in research and dissecting frogs, but with no inclination to follow in his father’s footsteps and become a physician. Allison was in jeopardy of not graduating high school after protesting his teacher’s decision not to teach evolution in class, because biology without Darwin was an impossibility. In the end, it was resolved through a correspondence course from a university, and Allison was able to proceed to higher studies and basic research within immunology. James P. Allison dedicated his lecture to all students, research colleagues, physicians and patients with whom he has worked. He spoke of how during the 1990s he had studied CTLA-4, a protein on the surface of the T cells. Early on, he had had an idea that it should be possible to deceive the body’s own immune system in order to attack tumour cells. Researchers at the time knew that CTLA-4 worked as one of the T cells’ brake pedals, and Allison developed a way to block CTLA-4 through treatment with an antibody that binds to the CTLA-4 protein. The T cells could then be released and thereby fight tumour cells. Cancer-free after receiving antibodies In 1994, Allison conducted the first experiment on mice, and in 2010 a study was published that showed good results in patients with disseminated malignant melanoma, or skin cancer. Among other things, Allison highlighted one case with a woman who was severely ill from skin cancer and who participated in a clinical study in 2001. No traditional cancer treatment had helped, and Allison shows a computed tomography image of her lungs which were full of metastases, or daughter tumours. The woman received a single antibody injection in the study. “At that point, the survival time after being diagnosed with metastatic malignant melanoma was eleven months, essentially a death sentence. In this computed tomography image ten years later we can see that all metastases in the woman’s lungs are gone. The woman is still cancer-free almost nineteen years later, it’s amazing,” says James P. Allison. The school thought his questions were too difficult Edvard Smith continued to introduce the second Nobel Laureate, Tasuku Honjo, born 1942, who grew up in Japan in difficult conditions surrounding World War II, yet still managed to educate himself. Like Allison, his time as a student at school was not without its complications. The teachers did not think that he was a good, obedient student because he often asked questions that were too difficult and found the school books to be too easy.  Tasuku Honjo likes music, museums and painting, tells Smith. He is also a devoted practitioner of tennis, baseball, basketball, table tennis and golf, with a handicap of 14. Every year he plays golf with the former Nobel Laureate from 2012, Shinya Yamanaka. To start with, Tasuku Honjo spoke about his father who was a surgeon and described his mother as his beautiful, warm-hearted guardian goddess. It was when the mother gave Honjo a biography of Hideyo Noguchi, a prominent physician and researcher in bacteriology and serology, that he decided to become a physician and then a researcher in immunology. “It’s a stroke of luck that people are fortunate enough to have an immune system with acquired immunity. Otherwise, cancer immunotherapy would have been an impossibility,” says Tasuku Honjo. Discovery of a protein with the same type of brake pedal In parallel with James P. Allison, Tasuku Honjo discovered that another protein, PD-1, which is also found on the surface of T cells, also acted as a brake pedal for the immune system. Animal experiments showed that blocking PD-1 was another possible strategy for cancer therapy.  The strategy proved to be very effective during clinical trials in 2012 and can be used to treat, for example, lung cancer, renal cancer, lymphoma and skin cancer. Additionally, a combination of blocking both PD-1 and CTLA-4 in skin cancer has been shown to have an even greater effect. As with Allison, Honjo referred to several cases where patients who had been close to death due to severe cancer had been cured using antibody therapy. Chart after chart depicts the levelling out of curves with increasing long-term survival. Paradigm shift within cancer therapy Tasuku Honjo described the arduous journey undertaken to understand the function of PD-1 and how the knowledge can be used. He compared the mechanisms of being able to brake and accelerate the immune system with the same functions in a car. At the same time, it is a tightrope act that must be performed when treating cancer with this method. “If you accelerate too much during cancer treatment, there is a risk that the body will have an autoimmune reaction and begin attacking itself,” says Tasuku Honjo. He proceeds to talk about the paradigm shift now taking place within cancer therapy. In addition to surgery, radiotherapy and chemotherapy, immunotherapy has been established as a fourth cornerstone in cancer treatment. The benefits, among other things, are that normal cells are not affected by the method, it is effective for many types of cancer (and more than 1,000 clinical trials are ongoing around the world) and the effect is lasting even after the treatment of patients has been discontinued. “Cancer will not completely disappear, but it can be controlled using immunotherapy, and it may become one of the many other chronic diseases that you can live with,” says Tasuku Honjo, who finished by humbly thanking all he had collaborated with through the years. Text: Helena Mayer  

His doctoral thesis covers the discontinued biobank initiative

Tue, 11/12/2018 - 14:30
Doctoral student Anthony Larsson will defend his doctoral thesis on 12 December at Karolinska Institutet.  The thesis covers the fate of biobank initiative BBMRI.se, which was ultimately discontinued by the Swedish Research Council following an investigation. In his thesis, Anthony Larsson describes why the initiative failed. However, his work began on completely different premises. Anthony Larsson was recruited to Karolinska Institutet, KI, in august 2011 and was employed as a doctoral student at KI in January 2012, to analyse the process of building a biobank infrastructure. But as time progressed, a lingering discontent was directed towards KI, which served as the host university for the biobank initiative, BBMRI.se. Some of the six other member universities that also participated in the initiative felt that KI gave itself undue favours. “I hope this thesis will provide a scientific contribution to something that is new and unchartered, such as this complex type of infrastructure that is spread across several geographic areas and buildings, but it may also be seen as a form of “cautionary tale” regarding what could happen if you fail to respond to warning signals in time,” says Anthony Larsson, doctoral student at the Department of Learning, Informatics, Management and Ethics (LIME) at Karolinska Institutet. A biobank stores human tissue samples and blood samples etc. for research purposes. When BBMRI.se (BioBanking and Molecular Resource Infrastructure of Sweden) was launched in 2009, it was the hitherto largest investment ever made in a medical infrastructure by the Swedish Research Council (VR) and was part of the EU-initiated umbrella organisation BBMRI.eu. Different interpretations about funding distribution BBMRI.se had a rather distinct structure with eight work packages, containing for example molecular analytics resources, ethics and law, biobanks informatics, physical biobanks, etc. “Reports were submitted to KI in a yearly basis, which in turn reported to VR. This meant that the organisation was very segmented and created some friction with the BBMRI.se management at KI because there were different interpretations as to how the funds were to be distributed,” says Anthony Larsson. Apart from literature studies, the core of his thesis is comprised by qualitative interviews with the organisation’s leading researchers, which allowed Anthony Larsson to follow the development. Further funding was halted After KI found itself on the receiving end of criticism, VR decided in 2016, following an internal and external investigation, to halt further funding and discontinue the venture. The critics alleged that KI did not adhere to the stipulations made by the consortium agreement as originally agreed upon. Already in VR’s first evaluation from 2012, it was indicated that there were unclear structures, particularly in relation to the host university, KI, and the other actors. As the discontent escalated, the premises for Anthony Larsson’s thesis were altered. From the outset there had been a common vision within BBMRI.se, but this dissipated in time. One of the articles in the thesis discusses what happens when actors in an organisation have different perceptions of the mission statement and act according to their own convictions. “When there’s no insight into what’s being done on an overarching level or in the other work packages, it leads to uncertainty, whereby actors  start pulling in different directions while only focussing on their own affairs, which leads to fragmentation in the organisation,” says Anthony Larsson. A problematic vertical-oriented organisation The thesis shows that a large part of the problem was that BBMRI.se had a vertical-oriented organisation without intermediate level feedback. “The organisation had needed more checks and balances during the different projects to ensure that it was progressing in the right direction. KI also reacted much too late to the criticism and much could have been resolved through talks,” says Anthony Larsson. The thesis work has not been without its challenges, especially after the VR decision to cancel further funding to BBMRI.se. “I’ve had to revise some my articles to get them to reflect the reality since the outcome was something altogether different, but this also made it more interesting and powerful,” says Anthony Larsson. New national organisation for biobanks in 2018 In 2018, BBMRI.se became part of a new national organisation for biobanks, Biobank Sweden, this time with Uppsala University as the host university. “Upon defending my thesis, I shall look forward to having an opportunity to discuss my dissertation and its outcome,” says Anthony Larsson. After obtaining his Ph.D., Anthony Larsson will continue his research on digitalisation  at the Stockholm School of Economics. He will also participate in a two-year research project, which seeks to understand how artificial intelligence may be used to affect the decision-making process for corporate boards in the future. Text: Helena Mayer

HPV type 16 or 18 in young women predicts risk of cervical cancer

Mon, 10/12/2018 - 06:01
The human papilloma virus (HPV) can cause cervical cancer. According to new guidelines in Sweden, women over thirty therefore undergo initial screening for the virus rather than a smear test. But younger women also have a much higher risk of pre-cancerous lesions if they carry HPV 16 or 18, a study from Karolinska Institutet in Sweden published in the scientific journal Cancer shows. Four out of five women of fertile age are infected at some time in their lives with HPV. Most of these infections clear on their own, but for some five per cent of the women, the infection turns chronic. Chronic HPV infection can cause pre-cancerous lesions and cancer of the cervix. HPV types 16 and 18 cause some 70 per cent of all cases of cervical cancer and the majority of high-grade pre-cancerous lesions. There are also several other high-risk HPV types that can cause pre-cancerous lesions and cervical cancer. So that doctors can catch pre-cancerous lesions in time, women in Sweden between the ages of 23 and 64 are screened using ectocervical smear tests. If the smear test is abnormal, the sample is tested for HPV. According to new guidelines, screening from the age of 32 is to take the form, in the first instance, of an HPV test instead. If the woman tests HPV positive, a cell sample is then taken that, if aberrant, occasions further gynaecological investigation. However, in the event of a normal cell test but a positive HPV test, the woman is invited only routinely to screening after three to seven years, depending on age. Normal smear tests are no guarantee “This is odd when we know that HPV is associated with cervical cancer,” says Sonia Andersson, professor of gynaecology at the Department of Women’s and Children’s Health, Karolinska Institutet. “So we wanted to examine the cervical cancer risk for patients with normal smear results.” The study included over 9,000 normal smear tests from women between the ages of 20 and 60 who took their tests under the Swedish screening programme from 2005 to 2007. During the follow-up period ending 2014, almost 100 of these women developed high-grade pre-cancerous lesions or in a few cases actual cervical cancer. These patients’ cell samples were then tested for HPV and compared individually with samples from healthy women. The researchers found that women over the age of 30 who were carriers of high-risk HPV had, regardless of HPV type, an eight times higher risk of developing high-grade pre-cancerous lesions or cancer than women with negative HPV findings. “Normal cell tests are therefore no guarantee that a woman won’t develop precancerous changes that can lead to cervical cancer,” says Professor Andersson. “So we need to follow up women with positive HPV findings more frequently.” Should test for HPV type Women below the age of 30 who tested positive for HPV types 16 and 18 had a much higher risk of developing high-grade pre-cancerous lesions or cervical cancer compared to women with negative HPV findings. The HPV tests used in screening programmes today do not show which type of HPV a woman is carrying, only that she has a high-risk type of the virus. “This should be changed. If we test for HPV type, we can screen low-risk individuals less often and instead follow up younger carriers of HPV 16 or 18 and older HPV-positive women more often. In the USA, they’re called in for a new HPV test within the year.” “It should be remembered that most HPV infections clear on their own, including HPV 16/18,” explains Professor Andersson. “But HPV is the most common risk factor for developing cervical cancer and should be followed up methodically. In this way, more pre-cancerous lesions can be treated on time and more cases of cancer prevented.” The study was conducted in association with the University of Ljubljana, Slovenia, and the Scientific Institute of Public Health in Brussels, Belgium and financed with grants from the Swedish Cancer Society, Karolinska Institutet, Stockholm County Council and the King Gustaf V Jubilee Foundation. Publication “The impact of HPV status on development of high-grade cervical intraepithelial neoplasia in women negative for intraepithelial lesions or malignancy at baseline: 9‐year Swedish nested case control follow‐up study” Maria Fröberg, Ellinor Östensson, Karen Belkić, Anja Oštrbenk, Mario Poljak, Miriam Mints, Marc Arbyn, Sonia Andersson. Cancer, online 10 December 2018, doi: 10.1002/cncr.31788.

Online CBT helps children with stomach pains

Fri, 07/12/2018 - 10:27
Cognitive behavioural therapy (CBT) online can be useful in treating gastrointestinal disorders in children when no physical cause can be found. This is the viewpoint of researchers at Karolinska Institutet in Sweden that is described in a new study published in the journal Clinical Gastroenterology and Hepatology.  About 13 per cent of all children suffer from FAPD (functional abdominal pain disorders), which means that they experience pain and other stomach symptoms without any clear physical cause. Many children with FAPD have a reduced quality of life and their families often seek medical care, resulting in large costs for society. So far there is no scientific evidence that medication or changes to their diet help children with these problems. Researchers at Karolinska Institutet have previously shown that online CBT can be effective for teenagers with irritable bowel syndrome (IBS), which is one of the diagnoses included in FAPD. Ninety children with FAPD from the whole of Sweden in the age group 8-12 took part in the new study, together with their parents. All the children were examined by a doctor and a psychologist before they participated in the study to check that they specifically had FAPD. The children were randomly assigned to either ten weeks of exposure-based online CBT or standard medical care. Several positive effects The results show that the children who accessed online CBT had an improved quality of life, fewer stomach problems and a reduced fear of symptoms, as well as avoiding fewer situations compared with children who received standard medical care. "Online CBT can be offered to patients regardless of where they live, and does not require them or their families to take time off school or work to undergo treatment," says Maria Lalouni, psychologist and researcher at the Department of Clinical Neuroscience at Karolinska Institutet, who carried out the study for her doctoral thesis. Children in the online CBT group were exposed to symptoms, i.e. they practised accepting the symptoms and coping with situations that they would normally prefer to avoid. Examples of exposure exercises were to eat food that produced symptoms (such as pizza or ice cream) or to go to school despite having a stomach ache. The parents were given the task of paying less attention to their children's symptoms and giving more attention to other things, such as participation in recreational activities. Families had the treatment in their homes and were able to contact a psychologist using text messages on an internet platform. Big cost savings Online CBT led to large savings in costs compared with standard medical care: on average SEK 9,500 for every child who participated in the online treatment over a ten-week period. These savings are partly from reduced healthcare consumption and partly from reduced indirect costs such as children’s absence from school and parents’ absence from work. "We show that online CBT can increase the accessibility of evidence-based healthcare for a large group of children with considerable suffering, at the same time as reducing costs for society,” says Ola Olén, consultant and researcher at the Department of Medicine, Solna, Karolinska Institutet, who led the study. The study was funded by the Jane and Dan Olsson Foundation, the Swedish Research Council, the Kempe-Carlgrenska Foundation, the Ruth and Richard Julins Foundation, Majblomman, ìShizu Matsumuraîs Donation, the Bengt Ihre Research Fellowship, the Swedish Society of Medicine, Forte, the Centre for Psychiatric Research, and ALF funds. Publication “Clinical and Cost Effectiveness of Online Cognitive Behavioral Therapy in Children with Functional Abdominal Pain Disorders” Maria Lalouni, Brjánn Ljótsson, Marianne Bonnert, Richard Ssegonja, Marc Benninga, Johan Bjureberg, Jens Högström, Hanna Sahlin, Magnus Simrén, Inna Feldman, Erik Hedman-Lagerlöf, Eva Serlachius and Ola Olén. Clinical Gastroenterology and Hepatology, online 28 November 2018, doi:  10.1016/j.cgh.2018.11.043

KI researchers to receive a third of the Swedish Research Council’s funding for clinical research

Thu, 06/12/2018 - 14:15
Researchers at KI are to be awarded over 37 percent of the Swedish Research Council’s funds granted for clinical treatment research in 2018. Of the 200 million kronor for the period 2019‑2021, no less than 75 million kronor is going to research at KI. The Council also granted funds for research into children’s and young people’s mental health. Out of a total of 137.4 million kronor in grants for the period 2018‑2023, almost 50 million kronor is going to KI researchers. The project grants went to the following researchers at KI: Jonas Bergh of the Department of Oncology-Pathology was awarded a total of 13.5 million kronor for the fine-adjustment of pre-operative system therapy and repeated therapy assessment; crossover-design in a prospective, randomised, phase II study for HER2-positive breast cancer. Annika Bergquist of the Department of Medicine, Huddinge, was awarded a total of 18.9 million kronor for her research into treatment with atorvastatin for primary sclerosing cholangitis (PSC) – a randomised controlled study.  Cecilia Ekeus of the Department of Women’s and Children’s Health was awarded a total of 300 thousand kronor for her research into neurological morbidity in children affected by cerebral haemorrhage in connection with suction cap delivery. Bo Göran Ericzon of the Department of Clinical Science, Intervention and technology was awarded a total of 18 million kronor for his research into immunotherapy with organ transplantation in order to minimise the need for immunosuppression.  Christina Dalman of the Department of Public Health Sciences was awarded a total of 24.9 million kronor for her research into early interventions in mental illness – How can barriers to care be overcome for newly-admitted children and young people?  David Mataix-Cols of the Department of Clinical Neuroscience was awarded a total of 4.7 million kronor for his research into clinical and cost-effectiveness of internet-mediated behavioural therapy for children and young people with Tourette’s syndrome. Ellenor Mittendorfer-Rutz of the Department of Clinical Neuroscience was awarded a total of 24.9 million kronor for her research into mental illness and social integration among immigrant children - causes, prognosis, prevention and treatment. Anna Norhammar of the Department of Medicine, Solna, was awarded a total of 19.5 million kronor for her research into myocardial infarction and starting metformin (MIMET) – a register-randomised controlled study.

Diabetes drug liraglutide linked to lower risk of cardiovascular events

Thu, 06/12/2018 - 07:00
Real world data from a large Nordic study shows that use of liraglutide, a drug for type 2 diabetes, is associated with a lower risk of myocardial infarction, stroke or cardiovascular death. The study, led by researchers from Karolinska Institutet in Sweden, is published in The Lancet Diabetes & Endocrinology. The number of patients with type 2 diabetes is increasing rapidly in the world. Cardiovascular disease is a serious complication of diabetes and represents a major cause of mortality in this patient group. Liraglutide, a diabetes medication, became available for clinical use in 2009. This drug is a glucagon-like peptide 1 receptor agonist that lowers blood sugar and reduces body weight. A large clinical trial published previously showed that liraglutide reduced the risk of major cardiovascular events among patients with diabetes who had established cardiovascular disease or were at high cardiovascular risk. It has been unclear if these findings also translate to cardiovascular benefit in the broad patient population seen in routine clinical practice. 46.000 patients included in the Nordic study The current study was a collaborative project between researchers at Karolinska Institutet in Sweden, Statens Serum Institut in Denmark, NTNU in Norway and the Swedish National Diabetes Register. The researchers used several nationwide registers with information on prescription drugs, diseases and other data from more than 46.000 patients in Sweden and Denmark, 2010–2016. Around 23.000 patients initiating treatment with liraglutide were compared with the same number of patients initiating treatment with another diabetes drug, DPP4 inhibitors. The main outcome in the study was major cardiovascular events, defined as myocardial infarction, stroke, or cardiovascular death. The rate of major cardiovascular events was 14.0 per 1000 person-years among patients using liraglutide and 15.4 per 1000 among patients using DPP4 inhibitors, a statistically significant difference. This corresponded to 5 fewer major cardiovascular events per 1000 patients followed up for 3 years. Reduced risk of cardiovascular death and any cause of death Use of liraglutide was also associated with reduced risk of cardiovascular death and any cause of death. In a subgroup analysis, patients with a history of major cardiovascular disease appeared to benefit most from treatment with liraglutide, although this was not a statistically significant difference compared with patients without such history. “Our study provides support for the cardiovascular effectiveness of liraglutide among a broader unselected group of patients, providing important confirmatory evidence from routine clinical practice. We believe it may be of interest to drug regulators, clinical guidelines, physicians, and patients,” says last author Björn Pasternak, senior researcher at the Department of Medicine, Solna, Karolinska Institutet, and affiliated with Statens Serum Institut. In addition to Björn Pasternak, the study was also led by Henrik Svanström, senior statistician, and Peter Ueda, postdoctoral researcher, both at the Department of Medicine, Solna, Karolinska Institutet. The study was conducted with support from the Heart and Lung Foundation, Novo Nordisk Foundation, Swedish Society for Medical Research, and the strategic research area in epidemiology at Karolinska Institutet. Publication "Use of liraglutide and risk of major cardiovascular events: a register-based cohort study in Denmark and Sweden" Henrik Svanström, Peter Ueda, Mads Melbye, Björn Eliasson, Ann-Marie Svensson, Stefan Franzén, Soffia Gudbjörnsdottir, Kristian Hveem, Christian Jonasson, Björn Pasternak. The Lancet Diabetes & Endocrinology, online 5 December 2018, doi: 10.1016/S2213-8587(18)30320-6   For more information, please contact: Björn Pasternak, senior researcher Department of Medicine, Solna, Karolinska Insitutet E-mail: bjorn.pasternak@ki.se Tel: 08-524 860 77 (contact through the press office)

New possible target for treating major common diseases

Tue, 04/12/2018 - 20:00
There is a large, untapped potential for developing drugs against cancer, fibrosis and cardiovascular diseases by targeting a family of receptors known as Frizzleds, researchers at Karolinska Institutet in Sweden believe. In a new study published in Science Signaling, they identify how these receptors are activated in the cell membrane and the processes that are then triggered within the cell. G protein-coupled receptors are one of the largest families of proteins, with some 800 representatives in humans of importance to a wide range of physiological functions. The receptors sit in the cell membrane and are activated by messenger molecules such as adrenalin, dopamine, histamine and endorphin, which trigger a cascade of processes within the cell. G protein-coupled receptors are involved in the progress of many diseases and are very common targets for drugs. Examples of drugs include beta blockers, antihistamines, morphine and L-DOPA. Many attractive targets “Since this is a large family of receptors, there are still many attractive but still unexploited targets for the future treatment of cancer, cardiovascular disease, diabetes, fibrosis and neurodegenerative diseases,” says Professor Gunnar Schulte at the Department of Physiology and Pharmacology at Karolinska Institutet. He is researching a group of G protein-coupled receptors called Frizzleds, which are important for numerous processes, including fetal development. Signaling via these receptors has also been linked to a large number of diseases, including different forms of tumour. There are currently no drug molecules in the clinics that affect Frizzled receptors, even though, structurally, they resemble the receptors that are effective targets for drug therapy. New screening method The new study shows that one of the receptors in the Frizzled family, Frizzled 5, could be targeted by drugs in the same way as histamine, adrenaline or dopamine receptors. Professor Schulte has led the research, which has been conducted in collaboration with Uppsala University and SciLifeLab in Sweden and research teams in Germany and Canada. The researchers also present a new method that can be used for screening substance libraries in the search for new drug molecules. “This opens up completely new opportunities and concepts for developing drugs for cancer, fibrosis and cardiovascular diseases based on targeting Frizzled proteins,” says Shane Wright, first author of the study and doctoral student in Professor Schulte’s research group at Karolinska Institutet. Better understanding of receptors Work on G protein-coupled receptors was recognized by the Nobel Committee in 2012 awarding the Nobel Prize in Chemistry to Brian Kobilka and Robert Lefkowitz. Recent technological developments have given scientists a better understanding of how G protein-coupled receptors and other receptors on the cell surface are activated and which processes are then triggered within the cell. Such information can prove vital to the development of new drugs.  “The reason there are no drug molecules that target Frizzled receptors is that these mechanisms are not fully understood, a situation that we hope to change,” says Professor Schulte. The study was financed by Karolinska Institutet, the Swedish Research Council, the Swedish Cancer Society, the Novo Nordisk Foundation, the Knut & Alice Wallenberg Foundation, the Engkvist Foundations, Marie Curie ITN WntsApp, the Swedish Society for Medical Research, the Science for Life Laboratory, Deutsche Forschungsgemeinschaft and the Canadian Institute for Health Research. Publication “FZD5 is a Gαq-coupled receptor that exhibits the functional hallmarks of prototypical GPCRs” Shane C. Wright, Maria Consuelo Alonso Cañizal, Tobias Benkel, Katharina Simon, Christian Le Gouill, Pierre Matricon, Yoon Namkung, Viktoria Lukasheva, Gabriele M. König, Stéphane A. Laporte, Jens Carlsson, Evi Kostenis, Michel Bouvier, Gunnar Schulte and Carsten Hoffmann Science Signaling, online 4 December 2018

ERC grants for research on MS, schizophrenia, and spider-silk fibers

Thu, 29/11/2018 - 14:24
Three researchers at Karolinska Institutet are being awarded prestigious grants from the European Research Council (ERC). Jens Hjerling Leffler, Anna Rising and Maja Jagodic each receive the ERC Consolidator Grant 2018 for research on, respectively, brain cell type-specific interactions in schizophrenia; the generation of artificial spider-silk super fibers; and epigenetics in multiple sclerosis. This funding programme awards up to EUR 2 million per project over a five year period, and is aimed at mid-career researchers who have recently started their own group and strive to strengthen their role as research leaders. Awarded researchers and projects at KI in 2018:   Principal investigator: Dr. Jens Hjerling Leffler, Department of Medical Biochemistry and Biophysics Project: Brain cell type-specific interactions and schizophrenia Summary: Schizophrenia is a devastating psychiatric disorder that is caused by many minor disturbances or variations in the regulation of hundreds of genes. This makes it difficult to understand where in the brain the most important errors occur, and if malfunctions in one type of cells can also cause pathological changes in adjacent cells. In the project now funded by the ERC, Dr. Jens Hjerling Leffler and his colleagues will investigate a new way of measuring the overall impact of the many minor genetic variations in specific cells, in both mice and humans. The researchers will then recreate this overall impact in only one type of brain cell in an otherwise healthy mouse, in order to be able to systematically investigate how disease-related changes in one cell can affect the function of nearby cells. Increased knowledge on how, when and where genetic changes lead to schizophrenia could hopefully contribute to the development of new therapies that can be used earlier in the disease process – or perhaps even before disease onset. More about Jens Hjerling Leffler’s research More about schizophrenia   Principal Investigator: Dr. Anna Rising, Department of Neurobiology, Care Sciences and Society. Project: Novel approaches to the generation of artificial spider-silk super fibers Summary: Spider silk is nature’s high performance material and has the potential to be used as a biomaterial for medical applications. However, production and spinning of artificial spider silk fibers are very challenging, and current methods to produce silk fibers include conditions which prevent the silk proteins from assembling into fibers in the same complex way that native silk proteins do. Recently, Dr. Anna Rising and her colleagues succeeded in spinning biomimetic spider silk using the same mild conditions as the spider does. In the project now funded by the ERC, the researchers will build further on these technical leaps – aiming to generate artificial silk fibers that are equal or superior to native spider silk in terms of toughness and tensile strength. To reach this goal, they will use genetic information and protein engineering to design new silk proteins, and decipher the relationships between protein structure and mechanical properties of the fibers. This information will be important not only for the generation of strong fibers, but also for the basic understanding of protein fibrillation in, for example, Alzheimer’s disease. More about Anna Rising’s research   Principal investigator: Dr. Maja Jagodic, Department of Clinical Neuroscience Project: Epi4MS – targeting the epigenome for a better understanding of disease pathogenesis and novel therapeutic strategies in Multiple Sclerosis  Summary: Multiple Sclerosis (MS) is a leading cause of incurable progressive disability in young adults. The Epi4MS project aims to identify epigenetic causes of MS and to develop novel therapeutic strategies based on inducing self-sustained reversal of aberrant epigenetic states. Dr. Maja Jagodic and her colleagues will utilize unique MS biomaterial combined with cutting-edge methodologies to capture relevant cells and measure their functional states. The impact of MS-associated changes will be evaluated using innovative in vitro epigenome screens. We will then utilize animal models to dissect the molecular mechanisms of MS-associated changes in vivo and test the therapeutic potential of targeted epigenome-editing. Epi4MS aims at a paradigm-shift in studying and treating complex inflammatory diseases. More about Maja Jagodic’s research About epigenetics at Wikipedia

A new KI Engagement Grant awarded to eight projects

Wed, 28/11/2018 - 10:19
Eight projects at Karolinska Institutet have been awarded the recently established KI Engagement Grants, which aim to help KI researchers get started along a path to societal impact. These grants are part of an internal ‘impact and outreach’ effort approved by KI President Ole Petter Ottersen. Research is increasingly being judged — by funding agencies and governments alike — not only on its scientific merit but also on its potential to have a tangible impact on society. And while it’s a given that academic research benefits society by creating new knowledge, using this new knowledge to directly benefit society at large, or co-creating new knowledge in a way that is most relevant to societal needs, requires that researchers actively engage with actors outside of academia. To promote such engagement activities, Grants Office set up the KI Engagement Grant, which is financed through government funds distributed to Swedish universities to promote the impact of research and education. The eight winners of the KI Engagement Grants 2018 were selected during the summer 2018 and have received up to SEK 200 000 for a period of up to one year (total budget for the call was SEK 1.2 million). A follow-up call within the framework of promoting KI’s impact will be announced next year. More about the KI Engagement Grant Awarded researchers and their projects:   Researcher: Pernilla Lagergren, Department of Molecular Medicine and Surgery Project: An oesophageal cancer day for stakeholders Summary: The KI Engagement Grant will be used to arrange a day with seminars, presentations and discussions for all patients who have been treated for oesophageal cancer, their relatives and clinical personnel working with these patients, as well as researchers in the field. This Oesophageal Cancer Day will be organised in Stockholm in spring 2019. Together with a patient collaborative group, the researchers will create an agenda with the most important subjects, to promote a better exchange of information and increase contact, networking and collaboration between the stakeholders.   Researcher: Ulrica von Thiele Schwarz, Department of Learning, Informatics, Management and Ethics Project: A structured approach to managing use of evidence-based methods in practice: co-creating a toolkit Summary: There is a substantial gap between what is known from research and what is done in practice. It is often challenging for healthcare professionals to translate research evidence such that it is useful in their context. To support professionals in this process, the researchers behind this project have written a book titled Användbar evidens (Useful evidence). Together with health- and social-care professionals, they will now create a hands-on, practical toolkit to facilitate a more structured decision process for the use of evidence-based interventions in health and social care. In this way, the material produced will contribute to making research more accessible and applicable.   Researcher: Zarina Nahar Kabir, Department of Neurobiology, Care Sciences and Society Project: Engaging family caregivers of persons with dementia and nurses in the development of a stress alleviating mobile application Summary: The study aims to assess feasibility of a mobile application — Stress Alleviating Mobile Application for Caregivers (SAMAC) — by collecting the views of dementia nurses and of caregivers of persons with dementia (PWD) on its use to alleviate caregivers’ stress and depressive symptoms. Dementia nurses and family caregivers of PWD will be engaged in developing the mobile application in terms of its content and features, and any other expectations of how it should function.   Researcher: Christoph Nowak, Department of Neurobiology, Care Sciences and Society Project: Engaging young people in diabetes epidemiology through popular social media influencers Summary: Research on the epidemiology of common cardiovascular and metabolic diseases, such as heart attack or diabetes, aims to identify risk factors for the disease as well as ways to prevent it. Getting young people to actively engage in these issues is crucial for many reasons; for example, for raising awareness of the risk factors and securing public support for future research. Whereas traditional media often does not engage young people, social-media profiles reach vast audiences among under-30-year-olds in Sweden. In this project, KI researcher Christoph Nowak aims to produce several videos together with at least one established social-media profile — a so-called influencer — to illustrate in an easy-to-understand way what his own research is all about, why it matters for young people, and how one can become a scientist. He will also engage with the audience through chat and website comments.   Researcher: Max Kleijberg, Department of Learning, Informatics, Management and Ethics Project: Studio DöBra toolbox Summary: DöBra Studio is an initiative with the goal of creating intergenerational meeting places and stimulating conversations between children and elderly people about dying, death, and loss. Various forms of art are used as tools to support these conversations. The initiative was developed as part of the DöBra research program in collaboration with community-based stakeholders, such as artistic organizations, activity centers for elderly people, and organizations for children. With support from the KI Engagement Grant, the stakeholders involved in DöBra Studio will work together to develop “DöBra Studio Toolbox” — a toolbox enabling others to develop similar initiatives as well as allowing stakeholders to disseminate the knowledge developed through this collaboration.   Researcher: Lena Wettergren, Department of Women’s and Children’s Health Project: Building partnership with stakeholders in the project Fex-Can; fertility and sexuality following cancer Summary: The Fex-Can research program has a co-creative track including an established long-term collaboration with a group of patient research partners. Researchers and patients have met regularly during the last four years to discuss the development of a web-based psycho-educational intervention that now is being tested in a randomized controlled trial. The KI Engagement Grant will fund an evaluation of this ongoing collaboration, through interviews with researchers and patient research partners, aiming to identify how to best sustain long-term engagement. The project group will also develop ways to engage a new group of stakeholders in a long-term collaboration: nurses and physicians working in cancer care.   Researcher: Anders Sönnerborg, Department of Medicine, Huddinge Project: Elements of an integrated and patient-centred approach to long-term care of people living with HIV Summary: Sweden is the first country in the world to reach the UNAIDS/WHO goal of HIV care, the so-called 90-90-90 goal. The KI Engagement Grant will support the dissemination of Sweden’s best practices in HIV care, with the aim of informing and inspiring the development and adoption of analogous approaches in the European arena. Specifically, a working group — comprising physicians and nurses with longstanding experience of HIV clinical care, academic HIV researchers, as well as representatives from the patient organisation HIV Sweden — will compile a report that analyses how these diverse actors have jointly achieved success in HIV care and how they will extend their research to address new challenges. The resulting report will be presented for the EU parliament at a special session on the 27th of November 2018.   Researchers: Agneta Richter Dahlfors and Ferdinand Choong, Department of Neuroscience Project: Art and gastronomy brings science to society Summary: Through the medium of art and gastronomy, Agneta Richter-Dahlfors and Ferdinand Choong at the Swedish Medical Nanoscience Center, Department of Neuroscience aim to establish a platform for two-way exchange between scientists and the public. They have developed a novel imaging technique (optotracing) that reveals the carbohydrates in plant tissues in striking, colourful images. The goal of this engagement project is ultimately to showcase this research by co-creating a public “Molecular Gastronomy Art Exhibition”, in which researchers present optotracing images of the carbohydrates in edible plants while well-known chefs give talks about ‘The New Conscious Kitchen’, a trending concept of sustainable, plant-based eating. The KI Engagement Grant will allow the researchers to prepare the ground: they will produce an image portfolio and initiate workshops with members of select communications channels to discuss image selection and refinement, as well as the next steps for making the exhibition a reality.

A new KI Engagement Grant awarded to eight projects

Tue, 27/11/2018 - 14:59
Eight projects at Karolinska Institutet have been awarded the recently established KI Engagement Grants, which aim to help KI researchers get started along a path to societal impact. These grants are part of an internal ‘impact and outreach’ effort approved by KI President Ole Petter Ottersen. Research is increasingly being judged — by funding agencies and governments alike — not only on its scientific merit but also on its potential to have a tangible impact on society. And while it’s a given that academic research benefits society by creating new knowledge, using this new knowledge to directly benefit society at large, or co-creating new knowledge in a way that is most relevant to societal needs, requires that researchers actively engage with actors outside of academia. To promote such engagement activities, Grants Office set up the KI Engagement Grant, which is financed through government funds distributed to Swedish universities to promote the impact of research and education. The eight winners of the KI Engagement Grants 2018 were selected during the summer 2018 and have received up to SEK 200 000 for a period of up to one year (total budget for the call was SEK 1.2 million). A follow-up call within the framework of promoting KI’s impact will be announced next year. More about the KI Engagement Grant Awarded researchers and their projects:   Researcher: Pernilla Lagergren, Department of Molecular Medicine and Surgery Project: An oesophageal cancer day for stakeholders Summary: The KI Engagement Grant will be used to arrange a day with seminars, presentations and discussions for all patients who have been treated for oesophageal cancer, their relatives and clinical personnel working with these patients, as well as researchers in the field. This Oesophageal Cancer Day will be organised in Stockholm in spring 2019. Together with a patient collaborative group, the researchers will create an agenda with the most important subjects, to promote a better exchange of information and increase contact, networking and collaboration between the stakeholders.   Researcher: Ulrica von Thiele Schwarz, Department of Learning, Informatics, Management and Ethics Project: A structured approach to managing use of evidence-based methods in practice: co-creating a toolkit Summary: There is a substantial gap between what is known from research and what is done in practice. It is often challenging for healthcare professionals to translate research evidence such that it is useful in their context. To support professionals in this process, the researchers behind this project have written a book titled Användbar evidens (Useful evidence). Together with health- and social-care professionals, they will now create a hands-on, practical toolkit to facilitate a more structured decision process for the use of evidence-based interventions in health and social care. In this way, the material produced will contribute to making research more accessible and applicable.   Researcher: Zarina Nahar Kabir, Department of Neurobiology, Care Sciences and Society Project: Engaging family caregivers of persons with dementia and nurses in the development of a stress alleviating mobile application Summary: The study aims to assess feasibility of a mobile application — Stress Alleviating Mobile Application for Caregivers (SAMAC) — by collecting the views of dementia nurses and of caregivers of persons with dementia (PWD) on its use to alleviate caregivers’ stress and depressive symptoms. Dementia nurses and family caregivers of PWD will be engaged in developing the mobile application in terms of its content and features, and any other expectations of how it should function.   Researcher: Christoph Nowak, Department of Neurobiology, Care Sciences and Society Project: Engaging young people in diabetes epidemiology through popular social media influencers Summary: Research on the epidemiology of common cardiovascular and metabolic diseases, such as heart attack or diabetes, aims to identify risk factors for the disease as well as ways to prevent it. Getting young people to actively engage in these issues is crucial for many reasons; for example, for raising awareness of the risk factors and securing public support for future research. Whereas traditional media often does not engage young people, social-media profiles reach vast audiences among under-30-year-olds in Sweden. In this project, KI researcher Christoph Nowak aims to produce several videos together with at least one established social-media profile — a so-called influencer — to illustrate in an easy-to-understand way what his own research is all about, why it matters for young people, and how one can become a scientist. He will also engage with the audience through chat and website comments.   Researcher: Max Kleijberg, Department of Learning, Informatics, Management and Ethics Project: Studio DöBra toolbox Summary: DöBra Studio is an initiative with the goal of creating intergenerational meeting places and stimulating conversations between children and elderly people about dying, death, and loss. Various forms of art are used as tools to support these conversations. The initiative was developed as part of the DöBra research program in collaboration with community-based stakeholders, such as artistic organizations, activity centers for elderly people, and organizations for children. With support from the KI Engagement Grant, the stakeholders involved in DöBra Studio will work together to develop “DöBra Studio Toolbox” — a toolbox enabling others to develop similar initiatives as well as allowing stakeholders to disseminate the knowledge developed through this collaboration.   Researcher: Lena Wettergren, Department of Women’s and Children’s Health Project: Building partnership with stakeholders in the project Fex-Can; fertility and sexuality following cancer Summary: The Fex-Can research program has a co-creative track including an established long-term collaboration with a group of patient research partners. Researchers and patients have met regularly during the last four years to discuss the development of a web-based psycho-educational intervention that now is being tested in a randomized controlled trial. The KI Engagement Grant will fund an evaluation of this ongoing collaboration, through interviews with researchers and patient research partners, aiming to identify how to best sustain long-term engagement. The project group will also develop ways to engage a new group of stakeholders in a long-term collaboration: nurses and physicians working in cancer care.   Researcher: Anders Sönnerborg, Deartment of Medicine, Huddinge Project: Elements of an integrated and patient-centred approach to long-term care of people living with HIV Summary: Sweden is the first country in the world to reach the UNAIDS/WHO goal of HIV care, the so-called 90-90-90 goal. The KI Engagement Grant will support the dissemination of Sweden’s best practices in HIV care, with the aim of informing and inspiring the development and adoption of analogous approaches in the European arena. Specifically, a working group — comprising physicians and nurses with longstanding experience of HIV clinical care, academic HIV researchers, as well as representatives from the patient organisation HIV Sweden — will compile a report that analyses how these diverse actors have jointly achieved success in HIV care and how they will extend their research to address new challenges. The resulting report will be presented for the EU parliament at a special session on the 27th of November 2018.   Researchers: Agneta Richter Dahlfors and Ferdinand Choong, Department of Neuroscience Project: Art and gastronomy brings science to society Summary: Through the medium of art and gastronomy, Agneta Richter-Dahlfors and Ferdinand Choong at the Swedish Medical Nanoscience Center, Department of Neuroscience aim to establish a platform for two-way exchange between scientists and the public. They have developed a novel imaging technique (optotracing) that reveals the carbohydrates in plant tissues in striking, colourful images. The goal of this engagement project is ultimately to showcase this research by co-creating a public “Molecular Gastronomy Art Exhibition”, in which researchers present optotracing images of the carbohydrates in edible plants while well-known chefs give talks about ‘The New Conscious Kitchen’, a trending concept of sustainable, plant-based eating. The KI Engagement Grant will allow the researchers to prepare the ground: they will produce an image portfolio and initiate workshops with members of select communications channels to discuss image selection and refinement, as well as the next steps for making the exhibition a reality.

Michel Sadelain lecture at Karolinska Institutet

Mon, 26/11/2018 - 11:46
In November 2018, Karolinska Institutet was visited by Michel Sadelain, a pioneer in the field of cancer immunotherapy called ”CAR T-cell therapy”. He visited KI for a symposium celebrating the ten year anniversary of Dr Åke Olsson's foundation for haematology research. Michel Sadelain is also director of the Center for Cell Engineering at the Memorial Sloan Kettering Cancer Center in New York. Here he tells us about his field of research.    

Genetic risk score for autism associated with outcome in CBT

Mon, 26/11/2018 - 09:59
Depression is a common disorder for which cognitive behavioural therapy (CBT) is the recommended treatment for most patients. Researchers at Karolinska Institutet have now studied how genetic factors relate to differences in outcome of CBT in 894 people with depression, and show for the first time how genetic risk scores is associated with CBT outcome. “Understanding how genetic variation effects the outcome of psychological treatment can help us understand why some people don’t respond to it,” says study-leader Christian Rück, psychiatrist and senior lecturer at the Department of Clinical Neuroscience, Karolinska Institutet. “Ultimately this can lead to improved treatment options.” All 894 participants in the study, which was published recently in the scientific journal Molecular Psychiatry, had been diagnosed with depression and had undergone a 12-week course of online CBT. Before the treatment, the researchers extracted their DNA from blood samples in order to analyze how outcomes correlated with genetic variation. This they did by comparing genetic variations in the participants with genetic risk scores for 6 different psychiatric conditions, education level and IQ. Risk score for autism A genetic risk score indicates how many genetic risk variants an individual has for a particular condition. Doing this, the researchers found that a higher genetic risk score for autism was associated with a poorer outcome after CBT for depression. This is the first time that genetic variation has been linked to outcomes of psychological treatment in a so-called genome-wide analysis – i.e. a study that analyses genetic variation across the entire genome.  The researchers are now aiming to substantiate their finding with new, larger studies. The study was conducted with the support of the internet psychiatry clinic of the Stockholm County Council, and the Swedish Research Council. Publication Genetics of response to cognitive behaviour therapy in adults with major depression: a preliminary report Evelyn Andersson, James J. Crowley, Nils Lindefors,  Brjánn Ljótsson, Erik Hedman-Lagerlöf, Julia Boberg, Samir El Alaoui,  Robert Karlsson, Yi Lu, Manuel Mattheisen, Anna K Kähler, Cecilia Svanborg,  David Mataix-Cols, Simon Mattsson, Erik Forsell, Viktor Kaldo, Martin Schalling, Catharina Lavebratt, Patrick F. Sullivan, Christian Rück Molecular Psychiatry, online 8 November 2018

Researchers hope to be able to replace dysfunctional brain cells

Mon, 19/11/2018 - 15:23
A new study by researchers at Karolinska Institutet supports the theory that replacement of dysfunctional immune cells in the brain has therapeutic potential for neurodegenerative diseases like ALS and Alzheimer’s disease. The study, which involved repopulating the brain with new immune cells in an experimental disease model, is published in Nature Communications. Macrophages are immune cells present throughout the body, and are specialised according to the organ in which they operate; in the brain they are known as microglia. In a healthy brain, microglia are involved in many caretaking functions that support the activities and health of nerve cells. In diseases like ALS and Alzheimer’s disease, microglia instead function to harm nerve cells. New model of microglia depletion The researchers behind the current study believe that replacement of the dysfunctional microglia with healthy cells will potentially be of therapeutic benefit in such neurodegenerative diseases. Therefore they have developed a new disease model in which the animal’s own microglia are removed from the central nervous system (CNS). This leads to a rapid influx of monocytes, precursors of macrophages, into the brain and spinal cord, giving rise to new microglia-like cells. Microglia in the brain, however, have a different embryonic origin to blood-borne monocytes. “We knew that blood monocytes would infiltrate the CNS in our experimental mouse model, but we did not know to what degree they would adapt to the new microenvironment,” says first author Harald Lund, a recently graduated doctoral student at the Department of Clinical Neuroscience, Karolinska Institutet. “So we dissected the process of repopulation and fully characterised what happened to these cells with time.” Nurture trumps nature The infiltrating cells adapted to the ‘empty’ tissue but did not fully differentiate into microglia. However, the monocytes started to express many genes characteristic of microglia, adopted their morphology and exhibited similar functions to microglia. A meta-analysis of several recent studies of microglia repopulation further confirmed the gene signatures as being specific to infiltrating monocytes adapting to the CNS microenvironment, which goes against their nature. The apparent dominance of the tissue microenvironment in dictating cell functionality could be exploited therapeutically, the researchers believe. The study provides support for the researchers’ current projects aiming to develop novel immunotherapies for neurodegenerative diseases. “There are several incurable neurodegenerative diseases in humans, but a complete lack of efficient immunotherapies,” says Professor Bob Harris at the Center for Molecular Medicine, Karolinska University Hospital and the Department of Clinical Neuroscience, Karolinska Institutet. “We believe that efficient replacement of dysfunctional microglia has the potential to be an effective therapy, so understanding the molecular events and consequences of repopulation of a microglia-depleted CNS are critical in working towards this goal.” The study was financed by the Swedish Alzheimer’s Foundation, the Swedish Research Council, the Margaretha af Ugglas Foundation, the Swedish Brain Foundation and Alltid Litt Sterkere. Publication “Competitive repopulation of an empty microglial niche yields functionally distinct subsets of microglia-like cells” Harald Lund, Melanie Pieber, Roham Parsa, Jinming Han, David Grommisch, Ewoud Ewing, Lara Kular, Maria Needhamsen, Alexander Espinosa, Emma Nilsson, Anna K. Överby, Oleg Butovsky, Maja Jagodic, Xing-Mei Zhang & Robert A. Harris Nature Communications, online 19 November 2018, doi: 10.1038/s41467-018-07295-7

Katarina Bjelke appointed new University Director at Karolinska Institutet

Fri, 16/11/2018 - 10:30
Katarina Bjelke is Karolinska Institutet’s new university director from May 2019. She is currently the university director at Uppsala University. “We’re delighted that Katarina wants to return to Karolinska Institutet, where she once began her career,” says Karolinska Institutet’s president Ole Petter Ottersen. “She has great experience from the academic sector and the Ministry of Education and Research. She also has many years’ experience of management, which makes her well-suited to lead the University Administration and develop the support it provides to our core activities research and education.”  Katarina Bjelke was formally the deputy director-general of the research policy unit at the Ministry of Education and Research. Before that she was head of the Division of Research and Doctoral Education, the International Unit and the Grants Office at Karolinska Institutet. She took her degree in dentistry in 1989 and earned her PhD in neuroanatomy from Karolinska Institutet in 1997. "I look forward to my new assignment and to come to Karolinska Institutet," says Katarina Bjelke. Katarina Bjelke takes up office in May 2019, replacing university director Per Bengtsson, who is due to retire.

Flaws in industry-funded pesticide evaluation

Fri, 16/11/2018 - 06:00
Academic researchers have examined raw data from a company-funded safety evaluation of the pesticide chlorpyrifos. They discovered an effect on the brain architecture of the exposed laboratory animals at all tested doses, which was not included in the reported conclusions. Karolinska Institutet in Sweden led this independent study, which is published in the scientific journal Environmental Health. All pesticides must be evaluated in terms of their safety and potential risks for human health before they can officially be approved. Normally the companies that manufacture the products cover the cost of such evaluations and commission test laboratories to perform the necessary animal tests. Assistant professor Axel Mie at Karolinska Institutet, Christina Rudén at Stockholm University and Philippe Grandjean at Harvard School of Public Health have examined a case in which independent research and company-funded tests deviated, at least in terms of the conclusions drawn in the industry-funded study. The company-funded animal test was performed to ascertain how neural development is affected by the pesticide chlorpyrifos, which is used on a wide variety of crops around the world, including some 20 EU countries (not, however, Sweden). The test laboratory concluded that there was no such effect, even at high doses. Several weak points “We have looked at the study design and raw data from the manufacturer-funded study and found several weak points,” says Axel Mie, assistant professor at Karolinska Institutet’s Department of Clinical Science and Education at the Stockholm South General (Söder) Hospital. “For instance, we observed a clear effect on the height of the cerebellum in young rats that were exposed to the substance while still at the fetal stage, even at the lowest tested dose. This was reported neither in the study’s summary nor in its conclusion.” Extensive independent research has also previously indicated that chlorpyrifos adversely affects brain development, including childhood IQ, even at the low doses that consumers are generally exposed to through food. “One conclusion we draw is that there is a risk that the results of industry-funded toxicity tests are not reported correctly,” says Dr Mie. “This makes it difficult for the authorities to evaluate the pesticides in a safe and valid way. We also conclude that independent academic research should be given a higher status in the evaluation of the safety of chemicals.” The researchers did not receive any external funding for the study. Publication “Safety of Safety Evaluation of Pesticides: Developmental neurotoxicity of chlorpyrifos and chlorpyrifos-methyl” Axel Mie, Christina Rudén and Philippe Grandjean Environmental Health, online 16 November 2018, doi: 10.1186/s12940-018-0421-y

New inflammation inhibitor discovered

Thu, 15/11/2018 - 20:00
A multidisciplinary team of researchers led from Karolinska Institutet in Sweden have developed an anti-inflammatory drug molecule with a new mechanism of action. By inhibiting a certain protein, the researchers were able to reduce the signals that trigger an inflammation. The study is published in Science and was done in collaboration with the University of Texas Medical Branch, Uppsala University and Stockholm University. “We’ve developed a new drug molecule that inhibits inflammation,” says Professor Thomas Helleday, at the Department of Oncology-Pathology, Karolinska Institutet, Sweden, who co-led the study with Dr Torkild Visnes and Dr Armando Cázares-Körner. “It acts on a protein that we believe is a general mechanism for how inflammation arises in cells.” The discovery is the result of many years of research by Thomas Helleday’s group on how DNA is repaired by the body. One of the objectives has been to fight cancer by targeting damage to the tumour cells’ DNA. Several breakthroughs have already been reported, which have led, amongst other things, to a new treatment for congenital breast and ovarian cancer using so-called PARP inhibitors, which has been available for some years.  Trials on mice It was when developing a new molecule for inhibiting the enzyme that repairs oxygen damage to DNA that the researchers found, to their surprise, that it also dampened inflammation. It turned out that the enzyme OGG1, apart from repairing DNA, also triggers inflammation.  The inhibitor blocks the release of inflammatory proteins, such as TNF alpha. In trials on mice with acute pulmonary disease, the researchers succeeded in dampening the inflammation. “This discovery could give rise to a new treatment for a very serious condition,” says Professor Helleday. “We’ll now be developing our OGG1 inhibitor and examining whether it can lead to new treatments for inflammatory diseases in order to cure or relieve diseases such as sepsis, COPD and severe asthma.” The discovery was made in collaboration with Professor Istvan Boldogh from the University of Texas Medical Branch, USA. The repair pathway on which OGG1 operates was discovered by Tomas Lindahl at Karolinska Institutet in the 1970s, an achievement that earned him the Nobel Prize in Chemistry in 2015. Collaboration between several universities The study was a collaboration between Karolinska Institutet, Uppsala University and Stockholm University in Sweden and the University of Texas Medical Branch, USA. It was financed by grants from Vinnova, the Knut and Alice Wallenberg Foundation, the Swedish Foundation for Strategic Research, the Swedish Research Council, the Swedish Cancer Society, the Swedish Childhood Cancer Foundation, the Swedish Pain Relief Foundation, the Torsten Söderberg Foundation, the National Institute of Allergic and Infectious Diseases (USA), the faculty of medicine and healthcare science at the Norwegian University of Science and Technology (NTNU), the Central Norway Regional Health Authority and the Svanhild and Arne Must Fund for Medical Research (Norway). Some of the authors, including Thomas Helleday, are listed as inventors on a US patent application for OGG1 inhibitors. The patent is owned by the Helleday Foundation, of which Thomas Helleday and co-author and KI researcher Ulrika Warpman Berglund are board members and through which they are involved in the development of OGG1 inhibitors for clinical application. Publication ”Small-molecule inhibitor of OGG1 suppresses pro-inflammatory gene expression and inflammation” Torkild Visnes, Armando Cázares-Körner, Wenjing Hao, Olov Wallner, Geoffrey Masuyer, Olga Loseva, Oliver Mortusewicz, Elisée Wiita, Antonio Sarno, Aleksandr Manoilov, Juan Astorga-Wells, Ann-Sofie Jemth, Lang Pan3, Kumar Sanjiv, Stella Karsten, Camilla Gokturk, Maurice Grube, Evert J. Homan, Bishoy M.F. Hanna, Cynthia B. J. Paulin, Therese Pham, Azita Rasti, Ulrika Warpman Berglund, Catharina von Nicolai, Carlos Benitez-Buelga, Tobias Koolmeister, Dag Ivanic, Petar Iliev, Martin Scobie, Hans E. Krokan, Pawel Baranczewski, Per Artursson, Mikael Altun, Annika Jenmalm Jensen, Christina Kalderén, Xueqing Ba, Roman A. Zubarev, Pål Stenmark, Istvan Boldogh and Thomas Helleday. Science, online 15 November 2018.

No link between hypoallergenic dogs and lower risk of childhood asthma

Thu, 15/11/2018 - 11:00
Growing up with dogs is linked to a lower risk of asthma, especially if the dogs are female, a new study from Karolinska Institutet and Uppsala University in Sweden shows. However, the researchers found no relation between ‘allergy friendly’ breeds and a lower risk of asthma. The study is published in the journal Scientific Reports. Earlier studies have demonstrated a link between growing up with dogs and a lower risk of childhood asthma, but it has not been known whether this association is modified by dog characteristics. In this new study, the researchers have interrogated how variables such as sex, breed, number of dogs or size of dog are associated with the risk of asthma and allergy amongst children raised in a home with a dog during their first year of life. “The sex of the dog can affect the amount of allergens released, and we know that uncastrated male dogs express more of a particular allergen than castrated dogs and female dogs,” says Tove Fall, Senior Lecturer at the Department of Medical Sciences – Molecular Epidemiology at Uppsala University, who led the study with Professor Catarina Almqvist Malmros at Karolinska Institutet. “Moreover, some breeds are described anecdotally as ‘hypoallergenic’ or ‘allergy friendly’ and are said to be more suitable for people with allergies, but there is no scientific evidence for this.” Classified by different traits The study included all children born in Sweden from 1 January 2001 to 31 December 2004 who had a dog in their home for the first year of life (23,600 individuals). Data from the Swedish population and health data registries were linked anonymously to two dog-owner registries from the Swedish Board of Agriculture and the Swedish Kennel Club. The dogs were classified by sex, breed, number, size and alleged ‘hypoallergenicity’. The researchers then studied the relationship between the dogs’ characteristics and the risk of asthma and allergy diagnosis or the prescription of asthma or allergy drugs at the age of six. The statistical analyses controlled for all known confounders that could affect the risk of developing asthma or allergies, such as parental asthma/allergy, geographical location and number of siblings. Their results showed that the prevalence of asthma at age six was 5.4 per cent. Children with only female dogs at home had a 16 per cent lower risk of asthma than those raised with male dogs. However, living with a male dog did not correlate with a higher risk than living with no dog at all. Children living with two or more dogs had a 21 per cent lower risk of asthma than those who only lived with one dog. Hypoallergenic dogs linked to higher risk of allergy Children of parents with asthma/allergies more often had breeds described as ‘hypoallergenic’ than children of parents without asthma/allergies – 11.7 per cent versus 7.6 per cent. Exposure to these breeds was associated with a 27 per cent higher risk of allergy but no increased risk of asthma. “The likely explanation for this higher risk is that families with a history of allergy to furred pets more often choose these dogs, and also that ‘allergy friendly’ dogs do not in fact release less allergens,” says Catarina Almqvist Malmros, Professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet and Consultant at Astrid Lindgren Children’s Hospital. “The finding should be treated with caution as we can say nothing about any actual causality,” she continues. “More studies are needed to monitor differences over time, measure the risk of allergies using biomarkers, and take account of the microflora.” The study was financed with grants from the Swedish Research Council, the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM), Agria, Forte, the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas), the Swedish Heart and Lung Foundation, Stockholm County Council (ALF funding) and the Strategic Research Programme in Epidemiology (SFO-epi) at Karolinska Institutet. Publication “Dog characteristics and future risk of asthma in children growing up with dogs” Tove Fall, Sara Ekberg, Cecilia Lundholm, Fang Fang and Catarina Almqvist Scientific Reports, online 15 November 2018, doi: 10.1038/s41598-018-35245-2.

Pages

1 2 3 4 5 6 7 8 9 next › last »