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: 1 hour 13 min ago

China first up as KI starts international alumni network

Wed, 24/01/2018 - 18:28
Karolinska Institutet is now starting organised international alumni networks for its overseas students. At its launch, the first of these, KI Alumni China, already has 50 members. “As alumni, we can provide a reliable platform for KI in the Chinese healthcare sector,” says Claire Ye, newly appointed alumni ambassador to China. Until now, Karolinska Institutet’s (KI) various departments have each dealt with their own overseas alumni in a variety of ways, but now KI is investing in an overall strategy for maintaining relationships with former students from around the world. On 22 January, a launch event was organized at Solna campus with approximately 80 participants. “Alumni are truly our most important tool for building collaboration and recruiting international students. We now have a structure in place for these contacts,” says Maria Masucci, deputy vice-chancellor for international affairs at Karolinska Institutet. She is also delighted to be able to offer students a basic professional network after graduation. Megan Osler, alumni coordinator at KI, is responsible for the practical administration of the project. She hopes that KI Alumni China will provide a working model for alumni networks in other countries. This year will see the launch of an alumni network in Vietnam, while Megan also sees a solid basis for future networks in Uganda, Columbia and Brazil. “The key is to have an ambassador in place, something we have in Vietnam,” she explains, and underlines that this is a voluntary position, even if KI can meet the costs of the organisation. It is no coincidence that China was first. Claire Ye from Shanghai completed her master’s in bioentrepreneurship at Karolinska Institutet between 2008-2010. Today, she works as senior manager of marketing, products and services at a newly opened private hospital that has gone from 20 to 500 employees in only two years. In 2012, Claire began to get in touch with KI alumni to create a network. There are currently around 50 members in various sectors of Chinese academia and business, all educated at KI. “When I returned home, I wanted to maintain contact with KI and wished that there was a network,” she says. Claire Ye sees several purposes behind KI Alumni China: For alumni, it is valuable to maintain contact with others who share the experience of studying at Karolinska Institutet in Sweden: “The experience we few share is unique once we have returned home.” It may prove even more important for current and future Chinese KI students: “They will be able to get advice from us about how they can get the most out of their time at KI, and how they should go about choosing a career once they return home,” says Claire Ye. For KI, this will be an important platform for student recruitment and collaboration with Chinese universities, hospitals and, eventually, businesses. “We want to build bridges for KI between Sweden and China, including commercial ties. This requires a little more effort but in the long-term will prove really valuable to Sweden and KI,” says Claire Ye. She believes that KI alumni can provide reliable contacts for Swedish businesses that wish to enter the Chinese life science and biotech markets. Ole Petter Ottersen, KI’s vice-chancellor and a guest at the dinner, concurs with Claire Ye’s assessment: “Karolinska Institutet has a clear ambition to maintain contacts with our Chinese students and alumni,” he says. For examples of Chinese alumni’s desire to maintain contact with KI after graduation, one need look no further than many video greetings from members of KI Alumni China played at the launch in Aula Medica. One of these was from 76-year-old Xu Qunyuan, previously a researcher and head of neuroscience at Capital Medical University and Chinese Minister of Health. Between 1981 and 1988, he was one of the first Chinese doctoral students at KI. Together with Megan Osler at KI, Claire Ye and three other KI alumni in Shanghai, Beijing and Shenzhen will now prepare an biotech markets. Ole Petter Ottersen, KI’s vice-chancellor and a guest at the dinner, concurs with Claire Ye’s assessment: “Karolinska Institutet has a clear ambition to maintain contacts with our Chinese students and alumni,” he says. For examples of Chinese alumni’s desire to maintain contact with KI after graduation, one need look no further than many video greetings from members of KI Alumni China played at the launch in Aula Medica. One of these was from 76-year-old Xu Qunyuan, previously a researcher and head of neuroscience at Capital Medical University and Chinese Minister of Health. Between 1981 and 1988, he was one of the first Chinese doctoral students at KI. Together with Megan Osler at KI, Claire Ye and three other KI alumni in Shanghai, Beijing and Shenzhen will now prepare an annual activity plan for the alumni network in China. Daily contact will mostly take place on social media, primarily on WeChat. “As a rule, we are people with fully-booked calendars, so it is a challenge to arrange meetings that sufficient numbers can attend,” says Claire Ye.  Megan Osler is delighted to see that organised collaboration is now underway: “Karolinska Institutet is a small university in a small, isolated country in a global backwater. However, because such a large proportion of our study courses are in English, we are a good choice for overseas students. And our alumni are an important channel for reaching them.” Text: Ulrika Fjällborg

Christer Betsholtz awarded the 2018 Louis-Jeantet Prize for Medicine

Tue, 23/01/2018 - 18:05
The 2018 Louis-Jeantet Prize for Medicine is awarded to Christer Betsholtz, Director of the Integrated Cardio Metabolic Centre at Karolinska Institutet, and Professor at Uppsala University. Christer Betsholtz is awarded the prize of SEK 5.8 million for his seminal discoveries in vascular biology, in particular the characterisation of specialised cells – pericytes – and their role in vascular development and permeability. The 2018 Louis-Jeantet Foundation grants the sum of CHF 700,000 for each of the two prizes, of which CHF 625,000 is for the continuation of the prize-winner's research and CHF 75,000 for their personal use.    

Silver Medal 2017 to Lars-Olof Wahlund and Eva Mattsson

Tue, 23/01/2018 - 11:57
Karolinska Institutet’s Silver Medal for 2017 is awarded to Lars-Olof Wahlund and Eva Mattsson. The medals are awarded to those who have made a special contribution to supporting KI’s activities. The vice-chancellor, in consultation with the pro-vice-chancellor, university director and the deans of research, doctoral education and higher education, awards Karolinska Institutet’s various medals based on recommendations from the Medals Committee. Extracts from the Committee’s reasons for awarding the silver medals: Lars-Olof Wahlund, senior professor in geriatrics, receives the medal for the major impact his work as a teacher, clinician and researcher has had on KI’s leading position in the field of dementia research. His scientific productivity is high, with in the region of 450 publications, and he is a leader within KI in the field of magnetic resonance-based research into dementia disorders.   Eva Mattsson, professor emerita in physiotherapy, receives the medal for her distinguished contribution to doctoral and higher education and research at Karolinska Institutet. Throughout the course of her professional life, she has been an eminent researcher who has influenced clinical praxis, as well as a forceful proponent of quality in first cycle, second cycle and doctoral education, not only in KI’s physiotherapy programme, but also within KI as a whole. The medals are being presented in conjunction with the “För nit och redlighet i rikets tjänst”, NOR, awarding ceremony, on 15 February.

Reduced dental anxiety among children with internet-based CBT

Tue, 23/01/2018 - 11:35
Researchers at Karolinska Institutet have developed an accessible therapy for children and adolescents suffering from dental phobia. The study, published in the Journal of Medical Internet Research, shows that guided internet-based CBT is highly effective in reducing anxiety and increasing the ability to deal with dental treatment. One year later, half of the children were completely free of their phobia. Dental anxiety often begins in childhood or adolescence, and can develop into a phobia with avoidance, strong negative feelings and thoughts aimed at dental care. Avoidance of dental care often leads to poor oral health, untreated caries or other dental problems. Cognitive behavioural therapy (CBT) is an effective treatment for most forms of specific phobia. However, with regard to children and adolescents with dental phobia, there are organisational, financial and geographic obstacles to providing such therapy. Researchers in this study have therefore developed an internet-based CBT treatment that they have tested in an open, uncontrolled study of 18 patients between the ages of 8 and 15. Treatment continued for 12 weeks During the study, participants used an internet platform to obtain weekly online guidance from a psychologist via a chat system. Treatment continued for 12 weeks and included texts, animations and dental-related video clips. The treatment also included an exercise package with a dental mirror, probe, local anaesthetic and cannula delivered to the home of the child/parent(s) with detailed instructions for the exercises. Through therapy and guidance from the psychologist, the home-based exercises were linked to real exposure and training visits to dental clinics around Sweden. The results show a statistically and clinically-significant increase in the children’s ability to manage dental treatment. The internet-based CBT also increased children’s and parents’ self-efficacy, led to fewer negative thoughts and reduced anxiety aimed at dental treatment. At a one-year follow up, 53 per cent of the children were completely free of their dental phobia. Surprisingly strong effects “Even though we expected positive effects from the therapy, it was still surprising to see the scope of improvement and the strong effects of the therapy among the patients, given that they did not have a single physical meeting with the psychologist,” explains Shervin Shahnavaz at Karolinska Institutet’s Department of Dental Medicine who is the researcher behind the development of the therapy. The researchers now hope to be able to repeat the results in an ongoing randomised controlled trial. “Internet-based CBT for dental phobia in children and adolescents may be an efficient form of therapy with the potential to increase access to effective treatment,” says Dr Shahnavaz. The study is the result of a collaboration with Stockholm County Council’s unit for internet psychiatry. The research project was supported with grants from SOF; board of dental research at Karolinska Institutet and Stockholm County Council and the Mayflower Charity Foundation for children. Publication Shahnavaz S, Hedman-Lagerlöf E, Hasselblad T, Reuterskiöld L, Kaldo V, Dahllöf G ”Internet-Based Cognitive Behavioral Therapy for Children and Adolescents With Dental Anxiety: Open Trial” J Med Internet Res 2018;20(1):e12, online 22 January 2018, doi:10.2196/jmir.7803

Two KI researchers accepted Wallenberg Clinical Fellows

Mon, 22/01/2018 - 13:57
Researchers Petter Brodin and Carl Sellgren Majkowitz at Karolinska Institutet have been accepted into the Wallenberg Clinical Fellows research programme, meaning a three-year appropriation financed by the Marianne and Marcus Wallenberg Foundation. Petter Brodin is an assistant professor at Karolinska Institutet’s Department of Medicine, Solna and Science for Life Laboratory, as well as a resident in paediatrics at the Karolinska University Hospital. His research deals with how the immune systems of infants are formed by environmental factors such as bacteria, viruses and nutritional components. Together with his research group, he has developed a completely unique experimental method based on a new sampling method. Carl Sellgren Majkowitz is a senior researcher at KI’s Department of Physiology and Pharmacology, as well as an attending physician at Karolinska University Hospital. Carl Sellgren Majkowitz and his research group are attempting to develop a new treatment for those suffering from schizophrenia and bipolar disorder that will cause fewer side effects than existing treatments. The purpose of the Wallenberg Clinical Fellows research programme is to stimulate clinical research among Swedish physicians and to identify the leading researchers of tomorrow in a clinical environment. The programme is primarily aimed at younger doctors. The initiative is the work of the Marianne and Marcus Wallenberg Foundation with scientific support from the Royal Swedish Academy of Sciences.

Demonstration for Ahmadreza Djalali

Fri, 19/01/2018 - 10:28
On Thursday, Amnesty International’s Swedish section and Karolinska Institutet held a joint demonstration in support of the physician and researcher Ahmadreza Djalali, currently facing a death sentence in Iran. The demonstration in support of Ahmadreza Djalali, who has been imprisoned in Iran since April 2016, was held at Campus Solna. Ahmadreza Djalali’s wife, Vida Mehrannia, also attended the demonstration. Ahmadreza Djalali was sentenced to death in October 2017 for alleged espionage on behalf of the Israeli government. Although Djalali is an Iranian citizen, he has a permanent residence permit in Sweden and was previously a researcher in disaster medicine at Karolinska Institutet, where he also defended his thesis in 2012. Amnesty International considers Ahmadreza Djalali to be a prisoner of conscience who has been arbitrarily imprisoned and is demanding that the Iranian authorities quash the sentence and release him. Ole Petter Ottersen, Vice-Chancellor of Karolinska Institutet, participated in the demonstration. Among other things, he spoke of the human right to a free and just trial, the fact that the death penalty conflicts with human dignity, human rights and international standards, as well as every value for which Karolinska Institutet stands. “As academics, we have a great responsibility towards the fight to abolish the death penalty and to maintain academic freedom, so let us make ourselves heard,” declared Ole Petter Ottersen. In 2014, during his time as vice-chancellor of the University of Oslo, Ole Petter Ottersen was instrumental in starting the Universities Against the Death Penalty network. During the demonstration, Anna Lindenfors, Director at Amnesty International Sweden, explained that, as the Supreme Court of Iran confirmed the death penalty in December, the only remaining possibility is a judicial review of the entire case that may change the verdict. “This is a very serious situation. Ahmadreza Djalali must be immediately and unconditionally released so that he can be reunited with his wife and children in Sweden and continue his research,” said Anna Lindenfors. Lisa Kurland, previously Djalali’s supervisor and professor in emergency care at Örebro University, contributed a more personal picture of her friend and colleague. “Ahmadreza Djalali travelled to Iran, the land of his birth and a country he loved, in order to pass on his knowledge. It pains me that he is imprisoned, and it is beyond comprehension that he is sentenced to death,” she said.   Text: Helena Mayer

Factor that doubles the risk of death from breast cancer identified

Fri, 19/01/2018 - 08:00
Researchers at Karolinska Institutet have discovered that the risk of death from breast cancer is twice as high for patients with high heterogeneity of the oestrogen receptor within the same tumour as compared to patients with low heterogeneity. The study, which is published in The Journal of the National Cancer Institute, also shows that the higher risk of death over a span of 25 years is independent of other known tumour markers and also holds true for Luminal A breast cancer, a subtype with a generally good prognosis. The most common form of breast cancer is oestrogen-receptor-positive, so called hormone-sensitive breast cancer. This means that the tumour needs the female hormone oestrogen to grow. Women who develop this kind of breast cancer have a remaining long-term risk of dying of the disease. It is also known that the oestrogen receptor can change when a breast cancer tumour spreads, which affects survival. Why this is the case, however, is not known, but a possible explanation is that there are tumour cells in one and the same tumour with varying degrees of expression of the oestrogen receptor. This is known as intra-tumour heterogeneity. In the present study, Swedish and American researchers sought to discover if breast cancer patients with high heterogeneity of the oestrogen receptor in their breast cancer tumour have a higher long-term risk of dying. To this end, they studied the fates of 593 patients in a clinical study, who had been either treated with tamoxifen or not treated with systemic therapy after surgery. All women had been diagnosed with post-menopausal oestrogen-receptor-positive breast cancer between 1976 and 1990. Independent of other known tumour markers “Our study shows that patients with high intra-tumour heterogeneity of the oestrogen receptor were twice as likely to die up to 25-years after their diagnoses as compared to patients with low heterogeneity,” says Linda Lindström, researcher at the Department of Biosciences and Nutrition, Karolinska Institutet. “And this was independent of whether or not they’d received tamoxifen and of other known tumour markers.” The researchers also discovered that the greater risk of death for patients with high intra-tumour heterogeneity also applied to patients with Luminal A breast cancer, a subtype of oestrogen-receptor-positive breast cancer that is considered to have a good prognosis. “Patients with Luminal A breast cancer and high intra-tumour heterogeneity of the oestrogen receptor were also twice as likely to die from the disease,” continues Dr Lindström. “This is interesting given that patients with Luminal A breast cancer subtype are generally thought to have a good prognosis. We believe that if validated, these new findings should be useable within the near future.” The study was financed by the Swedish Research Council, the Cancer Society in Stockholm, the Gösta Milton Donation Fund and the California Breast Cancer Research Program BCRP award. Co-author Laura J. van’t Veer, is a founder, shareholder and part-time employee of Agendia. Publication ”Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer” Linda S. Lindström, Christina Yau, Kamila Czene, Carlie K. Thompson, Katherine A. Hoadley, Laura J. van’t Veer, Ron Balassanian, John W. Bishop, Philip M. Carpenter, Yunn-Yi Chen, Brian Datnow, Farnaz Hasteh, Gregor Krings, Fritz Lin, Yanhong Zhang, Bo Nordenskjöld, Olle Stål, Christopher C. Benz, Tommy Fornander, Alexander D. Borowsky, Laura J. Esserman Journal of The National Cancer Institute, online 19 January 2018, doi: 10.1093/jnci/djx270

Flying membrane protein aids cancer drug design

Thu, 18/01/2018 - 18:00
Researchers at Karolinska Institutet, Uppsala University and the University of Oxford, have used a new strategy to understand how specific enzymes can be shut down to stop cells from dividing. The method, published in Cell Chemical Biology, allows scientists to better target an enzyme to fight cancer. Turning off enzymes that are important for the survival of growing cells is a promising strategy to fight cancer. But to be able to shut down only one specific enzyme out of thousands in the body, drugs have to be tailored to exactly fit their target. This is particularly difficult for membrane proteins, since they only function when incorporated into the cell lipid envelope, and often cannot be studied in isolation. In a study published in Cell Chemical Biology this week, researchers from Karolinska Institutet, KTH, Uppsala University, and the University of Oxford, used a new strategy to find out how anticancer drugs bind to the membrane protein dehydroorotate dehydrogenase (DHODH), a new cancer target. The groups of Sir David Lane and Sonia Lain at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet used native mass spectometry, a technique where a protein is gently removed from its normal environment and accelerated into a vacuum chamber. By measuring the time it takes for the protein to fly through the chamber, it is possible to determine its exact weight, which can, in turn, indicate whether the protein has bonded to another molecule and if so, what kind. The researchers used this highly accurate ”molecule scale” to see how drugs and lipids, the building blocks of the cell membrane, bind to DHODH. "We saw that one of the drugs seemed to bind better to the enzyme when lipid-like molecules were present", says assistant professor Michael Landreh. The team also found that DHODH binds a particular kind of lipid present in the cell’s power plant, the mitochondrial respiratory chain complex. "This means the enzyme might use special lipids to find its correct place on the membrane", Michael Landreh explains. To understand how lipids can help a drug recognize its target, the researchers worked with Dr Erik Marklund, group leader at the Department of Chemistry, Uppsala University, to build and compare computational models of free as well as membrane-bound DHODH. "The study helps to explain why some drugs bind differently to isolated proteins and proteins that are inside cells. By studying the native structures and mechanisms for cancer targets, it may become possible to exploit their most distinct features to design new, more selective therapeutics", says Sir David Lane, professor at the Department of Microbiology, Tumor and Cell Biology. The research was financed by: The Swedish Research Council, The Foundation for Strategic Research, the European Research Council, and Karolinska Institutet. Publication "Lipids shape the electron acceptor-binding site of the peripheral membrane protein dihydroorotate dehydrogenase," Costeira-Paulo J, Gault J, Popova G, Ladds M.J.G.W., van Leeuwen IMM, Sarr M, Olsson A, Lane DP, Laín S, Marklund EG, and Landreh M Cell Chemical Biology, online 18 January 2018 doi: 10.1016/j.chembiol.2017.12.012

Iceland’s president visits Karolinska Institutet

Thu, 18/01/2018 - 14:00
Icelandic President Guðni Thorlacius Jóhannesson and his wife Eliza Reid visited Karolinska Institutet on 18 January together with the Swedish King and Queen. KI and Iceland have enjoyed many years of collaboration, both in research and student exchanges. The visit to Karolinska Institutet (KI) took place as part of a three-day state visit to Sweden and, in addition to the royal couple, the President and First Lady were also accompanied by Karin Röding, State Secretary to the Minister for Higher Education and Research and former university director of KI. During a seminar at Nobel Forum, KI’s vice-chancellor Ole Petter Ottersen began by presenting KI and the university’s cooperation with Iceland. Around two percent of KI’s publications are the result of collaboration with researchers at Icelandic institutions, a notably high figure in relation to Iceland’s population. KI also has a number of student-exchange agreements with the University of Iceland. After a speech by Professor Anna Wedell, Chair of the Nobel Committee for Physiology or Medicine, presentations were made of research collaborations. Among the speakers was Unnur Valdimarsdottir, visiting professor at KI’s Department of Medical Epidemiology and Biostatistics, who presented her StressGene research programme, dealing with understanding the role played by genetic factors in the risk of serious illness and death resulting from psychological stress and difficult life events. Inga Dóra Sigfúsdóttir, visiting professor at the Department of Public Health Sciences, presented her research on risk and protective factors for health among young people, and also spoke about Iceland’s successful efforts to reduce smoking, drinking and drug use among young people. Frieder Braunschweig, associate professor in cardiology at the Department of Medicine, Solna, explained that many Icelandic physicians complete their doctoral education at Karolinska University Hospital and that, together with Karolinska University Hospital, KI researchers also collaborate closely in the field of cardiology with Landspitali - The National University Hospital of Iceland, both with regard to research, education and clinical care. Text: Helena Mayer

“Start cells” in the midbrain control whether we walk or run

Wed, 17/01/2018 - 19:00
A study by researchers at Karolinska Institutet and the University of Copenhagen published in Nature provides new and important knowledge about how the brain controls locomotion. In research on mice, scientists have discovered that specific start cells in various locations in the brainstem control whether the mouse walks or runs. This research may lead to new treatments for diseases and injuries that adversely affect locomotion. Locomotion, or the ability to move from one place to another is a fundamental and necessary function for the survival of both people and animals. Locomotor behaviour is episodic in character, meaning that we move as and when we want or need to, and that we are able to easily interrupt ongoing movements. At the same time, locomotion is executed at different speeds to regulate how fast we travel from one place to another depending on the context or purpose that drives us e.g. slowly exploring the neighborhood in a new city or fast escaping an oncoming threat.  The precise coordination of locomotion is controlled by neural circuits in the spinal cord, but it is the brainstem that sends signals to the spinal cord to initiate, stop and modulate these movements. Still, how is the start and speed control executed? By which command pathways? And can these command pathways be recruited to support different types of locomotion dependent on the behavioural context? Part of a larger neural network In the present study, the researchers Vittorio Caggiano, Roberto Leiras, Haizea Goñi-Erro, Debora Masini, and colleagues together with Professor Ole Kiehn who led the study, address these questions. They have identified specific “start cells” that are important for initiation, speed and context dependent selection of locomotion in mice. These ‘start cells’ are part of a larger neural network located in two different areas of the midbrain, the pedunculopontine nucleus (PPN) and the cuneiform nucleus (CnF).  “By identifying the midbrain ‘start neurons’ we complement a previous study in which we discovered specific ‘stop cells’ in the brainstem that perform the opposite task of making the mouse stop. Together, these cell types appear to be crucial to the episodic control of locomotive behaviour,” explains Professor Ole Kiehn, who works both at Karolinska Institutet’s Department of Neuroscience and at the Department of Neuroscience at the University of Copenhagen. Used light and designer drugs The researchers have utilised a number of advanced techniques, including optogenetics, to study which types of neurons are involved and the location of the neural networks. By using light and designer drugs, they have been able to activate or inactivate selected groups of nerve cells and then study how this affects the locomotor output in mice. They found that, in contrast to what has previously been thought, excitatory projection neurons in both PPN and CnF can start locomotion and contribute to the maintenance and speed regulation of slower locomotion. However, only CnF is able to elicit high-speed escape locomotor activity. In contrast, activity in PPN neurons favours explorative locomotion. “We have demonstrated that both brain regions collaborate and work independently of one another to select the gait and speed of locomotion,” says Ole Kiehn. Could be similar mechanisms in humans The researchers believe that similar mechanisms are at work in the selection of locomotion and speed in humans. The results of the study can therefore be important in developing treatments for spinal cord injuries and certain diseases that adversely affect locomotion. Parkinson’s Disease, where gait disturbances and freezing of gait are very pronounced, affects an area of the brain that sends signals to the PPN. By implanting fine electrodes in the brain – a technique called deep brain stimulation which is already used to treat some symptoms in Parkinson’s disease – circuits in either CnF or PPN might now be targeted with new precision and used to increase the locomotor capabilities. Similar approaches may also be used after damage to the spinal cord, where initiation of locomotion is strongly affected. The research was funded by the European Research Council (LocomotorIntegration), the US National Institute of Neurological Disorders and Stroke, The Swedish Research Council, StratNeuro and the Novo Nordisk Foundation- Laureate Award. Publication “Midbrain circuits that set locomotor speed and gait selection” Caggiano V, Leiras R, Goñi-Erro H, Masini D, Bellardita C, Bouvier J, Caldeira V, Fisone G & Kiehn O Nature, online 17 January 2018, doi: 10.1038/nature25448

KI researcher receives AFA Insurance work environment and health grant

Wed, 17/01/2018 - 15:55
Elisabeth Björk Brämberg, Assistant Professor at Karolinska Institutet’s Institute of Environmental Medicine, has been awarded a grant of approximately SEK 1.75 million for work environment and health-related research. Elisabeth Björk Brämberg’s research project: Enabling and constraining factors and ethical aspects related to cooperation aimed at increased return-to-work among people suffering from mental disorders. In this project, Elisabeth Björk Brämberg will, through interviews with employees, employers and representatives of healthcare centres, OHS providers and the Swedish Social Insurance Agency, collect and analyse experiences gained in collaborations connected with mental illness. The project includes the analyses of ethical issues linked to areas such as the health, personal rights and freedoms of those on extended sick leave and their ability to influence activities. One goal is the development of strategies to promote cooperation as a rehabilitation method. In the current round of grants, AFA Insurance has committed almost SEK 22 million to 10 new research projects in Sweden, aimed at contributing to a reduction in work-related injuries and long-term sick leave.

New way to target the growth of breast cancer cells

Wed, 17/01/2018 - 13:48
An international team of researchers led from Karolinska Institutet and Science for Life Laboratory have found a new way of halting the growth of breast cancer cells. In their study, which is published in Nature Communications, the researchers explore a new way to starve cancer cells from their molecular energy source. They hope that their discoveries can be further developed into a new way of treating breast cancer, and possibly other types of cancer. Breast and prostate cancer are the most common forms of cancer in Sweden, and the number of cases is increasing yearly. Often, these tumours use hormones, such as oestrogen or testosterone, to drive their growth, and thus normal treatments aim to block the activity of these hormones. While modern treatments are often successful, cancers can also become resistant to these treatments and develop new ways of propagating. In the current study, the researchers confirmed that hormone-driven breast cancer cells use a newly discovered protein, NUDT5, to produce energy in the cell nucleus. This nuclear energy source provides energy for the expression of genes that drive cancer growth. In the next stage of their research, they developed a molecule able to block NUDT5 activity and thus deprive the cancer cells of their means of nuclear energy production. They demonstrated that this new molecule can stop the growth of breast cancer cells in isolated laboratory experiments. Can hopefully help improve treatment options The original purpose of the project was to understand the biological function of NUDT5, but this has now shifted and the aim is to progress NUDT5 inhibitors towards clinical testing where these molecules can hopefully help improve treatment options for cancer patients. “They’re exciting findings, but the path ahead is long since we still know very little about how NUDT5 operates,” says Professor Thomas Helleday at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet. The study was led by researchers at Karolinska Institutet and SciLifeLab in association with colleagues from Stockholm and Uppsala universities and a team of Spanish researchers. Its main sources of funding were the Torsten Söderberg and Ragnar Söderberg foundations and the Knut and Alice Wallenberg Foundation. Publication “Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells” Page BDG, Valerie NCK, Wright RHG, Wallner O, Isaksson R, Carter M, Rudd SG, Loseva O, Jemth A-S, Almlöf I, Font-Mateu J, Llona-Minguez S, Baranczewski P, Jeppsson F, Homan E, Almqvist H, Axelsson H, Regmi S, Gustavsson A-L, Lundbäck T, Scobie M, Strömberg K, Stenmark P, Beato M, Helleday T Nature Communications, online 17 January 2018, doi: 10.1038/s41467-017-02293-7

Oxysterols guide gut immune cells and are involved in inflammatory bowel disease

Tue, 16/01/2018 - 15:32
Researchers at Karolinska Institutet report that cholesterol metabolites cause specific immune cells in the large intestine to move, which lies behind the formation of the immune system's important lymphoid tissue in the intestine. The study, published in the journal Immunity, paves the way for a new possible treatment for patients with inflammatory bowel disease. Inflammatory bowel disease is a common and severe disease that has no cure. Normally, the immune cells of the gut accumulate and communicate with each other in the lymphoid tissue. But, for those who have autoimmune inflammatory bowel disease, such as ulcerative colitis, the lymphoid tissue can react to the body's own cells and cause chronic inflammation. Hitherto, it has not been known which signals control the formation of the lymphoid tissue in the large intestine. But, now scientists at Karolinska Institutet have discovered that cholesterol metabolites, called oxysterols, stimulate specific immune cells in the large intestine, called innate lymphoid cells (ILCs), to form lymphoid tissue in both health and in disease. “We have discovered that ILCs use a surface protein called GPR183 to sense the oxysterols, which attracts ILCs to specific sites in the large intestine where lymphoid tissue is formed,” says Tim Willinger, researcher at Karolinska Institutet’s Department of Medicine in Huddinge, who has led the study. “Our findings are relevant to humans because inflammatory lymphoid tissue contributes to tissue damage in inflammatory bowel disease. We have discovered that patients with ulcerative colitis have higher levels of oxysterol-producing enzymes than healthy controls. The results indicate that oxysterols and GPR183 are involved in ulcerative colitis,” he says. One way to treat inflammatory bowel disease could, therefore, be to attempt to inhibit GPR183 or oxysterol production. “This treatment option is attractive, because GPR183 belongs to a group of molecules that are excellent targets for drug treatment,” says Dr Willinger. The study was financed by a Junior Investigator Research Grant from the Center for Innovative Medicine (CIMED) from Karolinska Institutet/Stockholm County Council. Publication ”Oxysterol sensing through the receptor GPR183 promotes the lymphoid tissue-inducing function of innate lymphoid cells and colonic inflammation”. Johanna Emgård, Hana Kammoun, Bethania García-Cassani, Julie Chesné, Sara M. Parigi, Jean-Marie Jacob, Hung-Wei Cheng, Elza Evren, Srustidhar Das, Paulo Czarnewski, Natalie Sleiers, Felipe Melo-Gonzalez, Egle Kvedaraite, Mattias Svensson, Elke Scandella, Matthew R. Hepworth, Samuel Huber, Burkhard Ludewig, Lucie Peduto, Eduardo J. Villablanca, Henrique Veiga-Fernandes, João P. Pereira, Richard A. Flavell, Tim Willinger. Immunity, online 16 January 2018.

Genetic analysis can improve depression therapy

Fri, 12/01/2018 - 08:11
The failure of drugs such as SSRIs, used to treat depression, can be a result of genetic variations in patients. Variations within the gene that encodes the CYP2C19 enzyme results in extreme differences in the levels of escitalopram achieved in patients, according to a new study published in The American Journal of Psychiatry. Prescribing the dose of escitalopram based on a patient’s specific genetic constitution would greatly improve therapeutic outcomes. The study was conducted at Karolinska Institutet in association with researchers at Diakonhjemmet Hospital in Oslo. Pharmaceutical treatment of depression commonly makes use of selective serotonin reuptake inhibitors (SSRIs) of which escitalopram is the most frequently administered clinically. However, escitalopram therapy is currently limited by the fact that some patients do not respond well to the drug, while others develop adverse reactions requiring discontinuation of treatment. In order to individualise drug therapy, researchers are attempting to establish genetic biomarkers that can predict an individual’s response to drugs. In a recent study, it was discovered that variation in the gene encoding the enzyme responsible for escitalopram metabolism (CYP2C19) is very important in this respect. Individuals with a variant of the gene promoting increased enzyme expression had blood levels of escitalopram too low to impact the depression symptoms, whereas patients with a defective CYP2C19 gene reached drug levels which were too high. Overall, one third of the 2,087 study participants achieved escitalopram blood levels that were either too high or too low. Many patients switched to other drugs Interestingly, the researchers found that 30 per cent of the patients carrying gene variants causing excessive or inadequate enzyme levels switched to other drugs within one year, in contrast with only 10 to 12 per cent of patients carrying the common gene. “Our study shows that genotyping of CYP2C19 could be of considerable clinical value in individualising doses of escitalopram so that a better all-round antidepressive effect could be achieved for the patients,” says Professor Magnus Ingelman-Sundberg at Karolinska Institutet’s Department of Physiology and Pharmacology who led the study together with Professor Espen Molden. “Because CYP2C19 is involved in the metabolism of many different SSRIs, the finding is also applicable to other types of antidepressants.” The study was financed with grants from the Swedish Brain Fund, the Swedish Research Council and Horizon 2020 (the EU framework programme for research and innovation). Co-author Espen Molden has declared a fee from the company Lundbeck for running psychopharmacology courses for doctors; the other authors have reported no commercial interests. Publication “Impact of CYP2C19 Genotype on Escitalopram Exposure and Therapeutic Failure: A Retrospective Study Based on 2,087 Patients” Marin M. Jukic, Tore Haslemo, Espen Molden, Magnus Ingelman-Sundberg The American Journal of Psychiatry, online 12 January 2018, doi: 10.1176/appi.ajp.2017.17050550

Proteomics analyses could present new opportunities to diagnose and treat dementias

Tue, 09/01/2018 - 09:00
One of the most intriguing properties of the brain is its means to undergo synaptic plasticity which represents the basis for learning and memory, abilities that severely decline in the case of a dementia. New research, published on 9 January in the scientific journal Brain, suggests that particular proteins important in the communication between neurons could be targets for early interventions in patients with different types of dementias. In the nervous system, a synapse is the place where signals are passed from neuron to neuron. The recently published paper focuses on synaptic dysfunction and its impact on dementia severity and cognition in the elderly with various dementia diagnoses. In addition to Alzheimer`s disease, the Lewy body dementias are the most common forms of neurodegenerative dementias with a very severe prognosis.  “Our findings suggest that particular pre- and postsynaptic proteins have an important predictive and discriminative molecular fingerprint in neurodegenerative diseases and represent potential targets for early disease intervention, such as synaptic regeneration,” Erika Bereczki says, first author of the publication and researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet. A new and broad perspective across dementias Synaptic loss, a prominent feature in Alzheimer`s disease is strongly correlated with dementia severity. Much less is known regarding synaptic loss in Lewy body dementias.  The study is the first in-depth quantitative proteome studies on pre-frontal post-mortem brain tissues where beside the whole proteome comparison, the researchers also profiled the entire synaptic proteome of Alzheimer`s disease, Parkinson`s disease with dementia and dementia with Lewy bodies patients and compared them to control cases. Taking benefit of the technological advance of proteomics analyses (a technique for large-scale studies of proteins) Erika Bereczki and her colleagues have identified key synaptic proteins underlying synaptic dysfunction which were associated with the degree of cognitive decline across dementias.  “Our results suggest shared mechanisms, with major implications for prognostic and diagnostic marker development as well as advancing future therapeutic interventions for improving the disease course. This places synaptic dysfunction and repair approaches in the spotlight of attention, especially since the therapeutic intervention window for synaptic repair and regeneration is longer than the recent toxin-clearance approaches”, Erika Bereczki says. Funding The study involved collaborators from Sweden, Norway, Hungary and the UK and was supported by grants from Alzheimerfonden, Parkinsonfonden, Demensfonden, Karolinska Institutet geriatric funds and UK Brains for Dementia Research among others. Publication Synaptic markers of cognitive decline in neurodegenerative diseases: a proteomic approach Brain, Published: 09 January 2018. Erika Bereczki, Rui M Branca, Paul T Francis, Joana B Pereira, Jean-Ha Baek, Tibor Hortobágyi, Bengt Winblad, Clive Ballard, Janne Lehtiö, Dag Aarsland

Mechanism that converts white fat to brown identified

Fri, 05/01/2018 - 16:01
An international team of researchers led from Karolinska Institutet have, in experiments on mice, pinpointed a mechanism for the conversion of energy-storing white fat into energy-expending brown fat. The study is published in the Journal of Experimental Medicine. Obesity is a major global health issue, affecting all age groups. Obesity increases the risk of several serious human diseases, including cardiovascular disease, type 2 diabetes and cancer. Despite this knowledge, effective drugs for the treatment of obesity and related metabolic disease are lacking. ​Scientists differentiate between white adipose tissue, which constitutes most human fat and which stores surplus energy, and brown adipose tissue, which generates heat by consuming energy. One possible way of tackling potential obesity, suggest researchers, is to stimulate the conversion of parts of the white fat into brown. Stimulating the formation of blood vessels in white adipose tissue In a new study conducted on obese mice, a research team led by Professor Yihai Cao Karolinska Institutet and their colleagues at the University of Connecticut and Qingdao University stimulated the formation of blood vessels in white adipose tissue by blocking the receptor molecule for a growth factor known as VEGFR1, an effect that was achieved in one group of mice by means of a drug, and on another through genetic modification. The result was an increase in the conversion of white fat to brown, as well as a reduction in obesity and improved sensitivity to insulin. “Our discoveries can hopefully help us to develop new drugs for the treatment of obesity and diabetes,” says Yihai Cao, professor in vascular biology at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet. Professor Cao´s research was financed by: The European Research Council, the Swedish Research Council, the Swedish Cancer Foundation, the Karolinska Institute Foundation, the Karolinska Institute distinguished professor award, the Torsten Soderberg Foundation, the Maud and Birger Gustavsson Foundation, the NOVO Nordisk Foundation and the Knut and Alice Wallenberg Foundation. Publication  Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning Seki T, Hosaka K, Fischer C, Lim S, Andersson P, Abe M, Iwamoto H, Gao Y, Wang X, Fong GH, Cao Y.  Journal of Experimental Medicine, online 5th of January 2018, doi:10.1084/jem.20171012.  

Research groups’ move to Bioclinicum delayed

Fri, 22/12/2017 - 11:11
According to the previous plan, research groups from Karolinska Institutet and Karolinska University Hospital were due to move into the new Bioclinicum research building on the hospital site in Solna in mid-January 2018. The NKS Programme Office, together with hospital management, have now decided to postpone the move due to the risk of the network in the research building interfering with the network in the already commissioned buildings, and thereby negatively impacting patient safety. Approximately 900 researchers will be affected by the delay. “Yesterday, we informed heads of departments whose researchers are specifically affected. This delay will affect a great many projects and will naturally be a cause of disappointment to many members of staff. We are maintaining an ongoing dialogue and will be announcing a new timetable for occupancy as soon as possible,” says Ole Petter Ottersen, Vice-Chancellor at Karolinska Institutet. Programme management at NKS is now reviewing the various factors affecting the delay and will then set a new date for occupancy. This announcement will be made after the coming weekend at the earliest. “It is extremely unfortunate that we are unable to carry out the relocation of research groups in January. A great many people have worked hard to prepare for the commissioning of the building, the move and the various projects that will be started once the move is complete. That said, patient safety must always come first, and this is the criteria by which we are evaluating the planning of the move. If we are unable to guarantee patient safety, we will not be able to take occupancy. Our task now is to identify the necessary measures as soon as possible and put in place a revised timetable for researchers to move into the new building,” says Stanley Holsteiner, director of the Programme Office. Network interference experienced during November made the problem apparent and resulted in both a review of the network as a whole, and a decision by hospital management to revisit the timetable. This review is currently underway under the leadership of the IT directors of Stockholm County Council and Karolinska University Hospital.

Salamander genome gives clues about unique regenerative ability

Fri, 22/12/2017 - 11:00
Researchers at Karolinska Institutet have managed to sequence the giant genome of a salamander, the Iberian ribbed newt, which is a full six times greater than the human genome. Amongst the early findings is a family of genes that can provide clues to the unique ability of salamanders to rebuild complex tissue, even body parts. The study is published in Nature Communications. This is the first time that an entire newt genome has been sequenced, an achievement that can give rise to new discoveries on the amphibian’s ability to recreate brain neurons as well as entire body parts. Amongst the first findings are a multitude of copies of a certain microRNA group, which in mammals is mainly found in embryonic stem cells, but also in tumour cells. Resistant to tumour formation “It will be exciting to figure out how regeneration in the adult organism re-activates embryonic genes,” says study leader Professor András Simon at Karolinska Institutet’s Department of Cell and Molecular Biology. “What’s needed now are functional studies of these microRNA molecules to understand their function in regeneration. The link to cancer cells is also very interesting, especially bearing in mind newts’ marked resistance to tumour formation.” Even though the abundance of stem cell microRNA genes is quite surprising, it alone cannot explain how salamanders regenerate so well. Professor Simon predicts that the explanation lies in a combination of genes unique to salamanders and how other more common genes orchestrate and control the actual regeneration process. Technical and methodological challenge One of the reasons why salamander genomes have not been sequenced before is its sheer size – six times bigger than the human genome in the case of the Iberian newt, which has posed an enormous technical and methodological challenge. “It’s only now that the technology is available to handle such a large genome,” says Professor Simon. “The sequencing per se doesn’t take that long – it’s recreating the genome from the sequences that’s so time consuming.” “We all realised how challenging it was going to be,” recounts first author Ahmed Elewa, postdoctoral fellow at the same department. “But the very fact that it was such a challenge made it all the more exciting.” Can recreate cells that die in Parkinson’s disease The group at Karolinska Institutet is now engaging with other researchers to discover what can be learned from the newt genome and test new hypotheses through systematic comparisons with mammals. “We showed ten years ago that salamanders can recreate all the cells that die in Parkinson’s disease in the space of four weeks,” says Professor Simon. “We can now delve deeply into the molecular processes underlying this ability. Although we’re doing basic research, our findings can hopefully lead to the development of new regenerative strategies for humans.” The sequencing project was conducted in collaboration with SciLifeLab and Uppsala University and was largely financed with grants from the Swedish Research Council, the National Institutes of Health (USA), the European Research Council, the Swedish Cancer Society and the Wenner-Gren Foundation. Publication “Reading and editing the Pleurodeles waltl genome reveals novel features of tetrapod regeneration” Ahmed Elewa, Heng Wang, Carlos Talavera-López, Alberto Joven, Gonçalo Brito, Anoop Kumar, L Shahul Hameed, May Penrad-Mobayed, Zeyu Yao, Neda Zamani, Yamen Abbas, Ilgar Abdullayev, Rickard Sandberg, Manfred Grabherr, Björn Andersson, András Simon Nature Communications, online 22 December 2017, doi: 10.1038/s41467-017-01964-9

KI Innovations and Karolinska Institutet make joint investment in increased utility

Fri, 15/12/2017 - 15:24
Karolinska Institutet is now taking the initiative to coordinate, develop and streamline support to researchers and students with regard to the utilisation and commercialisation of research results. This will take place through KI Innovations, in addition to its existing activities, taking on the task of running KI’s Innovation Office. Previously, KI Innovation’s organisation has focused on business consultancy, marketing and patent issues and commercial development. Agreement has now been reached to expand these activities to include the management of KI’s Innovation Office. This important assignment will require increased communication with KI’s organisation, focusing on inspiration, consultancy and guidance to researchers, students and other staff engaged in developing ideas and dealing with innovation issues. The purpose is to increase awareness of these opportunities, and to publicise the results among both staff and students at KI. In addition, this year KI Innovations qualified for Vinnova’s incubator excellence programme, making it possible to offer development support to startups in the life science sector. Together, these three roles will be integrated to contribute to a more efficient innovation programme, with the goal of achieving increased utility and commercialisation of both research results and other ideas generated by staff and students. In order to clarify the importance of an innovation system that is clearly integrated with KI’s organisation, as of 2018 these activities will be run from new premises at Berzelius väg 3, in the heart of the campus. About KI Innovations Karolinska Instsitutet Innovations AB is a wholly-owned subsidiary of Karolinska Institutet’s holding company. KI Innovations assists in the commercialisation of research results in the field of life science. Karolinska Institutet’s innovation support includes consultancy, training, guidance, professional networking, financing, expertise in entrepreneurship and business development and incubation opportunities for projects and companies in the life science sector.

Karolinska Institutet receives three new Wallenberg Academy Fellows

Thu, 14/12/2017 - 10:11
Three researchers at Karolinska Institutet have been appointed Wallenberg Academy Fellows 2017. The three researchers are Emanuela Santini, Carmen Gerlach and Joanna Rorbach, all in the field of medicine. In total this year, 24 young researchers receive this prestigious award and funding by Knut and Alice Wallenberg Foundation. The purpose of the Wallenberg Academy Fellowship programme is to boost Sweden as a research nation by retaining the greatest talents in the country and by recruiting young international researchers to Swedish universities. Via an integral mentor program, they also have an opportunity to strengthen their scientific leadership and better utilize their research results. The program has been established in partnership with the royal academies and 16 Swedish universities. The investment provides the best young researchers with long-term resources so that they can concentrate on their research. “It is particularly pleasing that there are as many women as men among this year’s Academy Fellows. Those who are appointed to be Wallenberg Academy Fellows go through a thorough evaluation process. First, the university nominates candidates; they are then reviewed by evaluation panels in each subject, which are led by the five royal academies,” says Peter Wallenberg Jr, Chairman of the Knut and Alice Wallenberg Foundation in a press release. Emanuela Santini Repetitive behaviours in autism. Emanuela Santini is today working at Columbia University in New York, but as Wallenberg Academy Fellow she will move her research to Karolinska Institutet. With the long-term goal of finding a treatment that subdues repetitive behaviors shown by some people with autism spectrum diagnoses, Emanuela Santini will investigate how they arise at a molecular level. Some people with autism repeat specific sounds, words or sentences, others bite their nails or spin around – behaviors that have a negative effect on quality of life, both for the sufferer and their relatives. Previous studies indicate that mutations in the eIF4E gene may be responsible; when Emanuela Santini overexpressed the equivalent gene in mice, they developed behaviors that were reminiscent of the repetitive symptoms of autism spectrum disorders. Her hypothesis is therefore that the change in eIF4E affects the signals between the nerve cells in the striatum, an area of the brain that controls how we move, among other things. More about Emanuela Santini's research Carmen Gerlach More effective vaccines and therapies against cancer. Carmen Gerlach, moving her research from Harvard Medical School to Karolinska Institutet, studies how the body’s immune system protects us from infections and combats cancer cells. As Wallenberg Academy Fellow she will investigate specific groups of immune cells, CD8 T cells, to better understand how they work. Current vaccines primarily activate cells that produce antibodies, and Carmen Gerlach will try to develop knowledge that can be used to design vaccines that also make the right types of CD8 T cells. The hope is, among other things, that such vaccines could provide protection from diseases for which current vaccines do no work. More about Carmen Gerlach's research Joanna Rorbach Mitochondrial ribosomes to be mapped in atomic detail. Joanna Rorbach is a principl investigator at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics. As Wallenberg Academy Fellow she will investigate the large molecular machinery in the mitochondria, the cell’s power plant that puts together the proteins used in cellular respiration. These molecular protein factories are called mitochondrial ribosomes and are central to our survival. However, despite their importance there is limited knowledge of how the mitochondrial ribosomes are built together and function. In her work, Joanna Rorbach will use the latest advancements in genetics and proteomics together with cryo-electron microscopy.  Beyond describing the workings of the cell nucleus in atomic detail, in-depth knowledge of mitochondrial ribosomes may contribute to further understanding of the mechanisms behind aging, cancer and many inherited and neurodegenerative diseases. More about Joanna Rorbach's research

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