Tag Archives: IKM

The Integrated University Hospital improves patient care

Blogger: Bjørn GustafssonBjørn_Gustafsson_blid_Foto_GeirMogen
Dean of Research, The Faculty of Medicine, NTNU

Last week one of our research groups, led by Professor Duan Chen, published a comprehensive scientific study showing promising results in treating gastric cancer, by blocking the tumor nerve supply. The article was published in the prestigious journal Science Translational Medicine.

From left: The Knowledge Center, Chun-Mei Zhao, Gøran T. Andersen (in the background), Duan Chen bottom right

From left: The Knowledge Center, Chun-Mei Zhao, Gøran T. Andersen (in the background), Duan Chen bottom right (Photo: Helsebygg/Geir Mogen)

The term “translational medicine” involves transferring new knowledge from basic research on for instance cell culture or animal models to practical use in patient care; also coined with the term “from bench-to-bedside”.

Continue reading

Leave a Comment

Filed under Cancer, NTNUmedicine, Opinions, Oral and Gastrointestinal, Research

CEMIR seminar in Trondheim, September 4, 2014

The Centre of Molecular Inflammation Research, CEMIR, will hold the annual scientific seminar on inflammation research on September 4, 2014.

Speakers include the renowned professors

Cemir collage seminar

Clockwise from top left: Alan Aderem, Göran Hansson, Stefanie Vogel and Douglas Golenbock

The invited speakers will relate to the inflammation research area in different ways.

The seminar is open for all and you do not need to register in avance to participate.

CEMIR was established in 2013 as a Centre of Excellence appointed by the Research Council of Norway. The vision of CEMIR is to lay the foundation for identifying new therapeutic targets and developing new diagnostic tools for inflammatory diseases through an integrated 10-year programme of research and research training in molecular innate immune responses. CEMIR is hosted by the Faculty of Medicine at the Norwegian University of Science and Technology (NTNU).

Please find the full seminar program and see the titles of the talks here: CEMIR seminar 2014 programme (pdf)

Leave a Comment

Filed under Inflammatory and Immune System, NTNUmedicine, Research

Treating cancer with botox

Gøran Andersen og Duan Chen.

Gøran Andersen and Duan Chen. (Foto: Geir Mogen)

In laboratory tests at The Faculty of medicine, NTNU, Botox proved highly effective at suppressing gastric cancer in mice.

The promising results have led to the launch of an early clinical trial involving human patients with stomach cancer in Norway and St. Olavs Hospital.

Leave a Comment

Filed under Cancer, NTNUmedicine, Research

Cortisone does not relieve cancer pain

Blogger: Ørnulf PaulsenØrnulf-Paulsen-WEB

Ørnulf Paulsen is a PhD student at European Palliative Care Research Centre, NTNU, and Senior Consultant in palliative medicine at Telemark Hospital

Until now, clinicians have assumed that corticosteroids effectively relieve pain in cancer patients. A new study shows that this is not the case.

The results from our study have recently been published in the acknowledged Journal of Clinical Oncology.

Placebo shows same effect

Corticosteroids are widely used for the most advanced cancer patients, and pain treatment is one of the indications. The pain relieving effect, however, has never been documented in research results. Our study showed that the drug had no pain relieving effect for the cancer patients who participated in the study.

Continue reading

Leave a Comment

Filed under Cancer, NTNUmedicine, Research

Ask a researcher: Is the 5:2 diet healthy for women?

Question

Is the 5:2 diet healthy for women?

 

Answer from Catia Martins Catia Martins. Photo: Geir Mogen

 

 

 

5:2 diet is a type of intermittent fasting, which involves a “feed day”, where food is consumed ad libitum over a 24-hours period, alternated with a “fast day” where food intake is completely or partially restricted over 24 hours. The fasting days usually vary between 2-4 days/week.

Continue reading

Leave a Comment

Filed under Metabolic and Endocrine, NTNUmedicine, Spør en forsker

Taking care of knowledge

Kuiper_TrondheimAstrid Lægreid. Foto: Geir MogenBloggers: Astrid Lægreid, professor, Department of Cancer Research and Molecular Medicine and Martin Kuiper professor, Department of Biology

 

 

 

It is often overlooked that after you publish your research results you have not necessarily provided your new knowledge to your colleagues in the best possible way. Today’s biomedical science is very much dependent on the use of computers, to analyse and integrate the various types of data and facts that you and your fellow scientists have produced.  And whereas a computer can do many things, it has difficulty in understanding what is so easily understood by us when we read a scientific publication.

Continue reading

Leave a Comment

Filed under NTNUmedicine, Research

How plague bacteria kill immune cells

PNAS cover

The article has the cover image for the current issue of PNAS. (May 20, 2014)

Many bacteria kill considerable numbers of host cells upon infection. However, the mechanisms behind the cell death are in many cases unclear. A recent article in PNAS by the the CEMIR-affiliated researcher professor Egil Lien,  describes how the bacteria Yersinia pestis, the causative agent of plague, kills key immune cells called macrophages by apoptosis mediated by kinase RIP1 and caspase-8 together with RIP3.

Apoptosis is often considered to be a “silent” type of cell death. However, we found that the death was accompanied by inflammatory processes via IL-18 and IL-1b generating inflammasomes and transcription factor NF-kB, also via RIP kinases and caspase-8. Importantly, mice deficient in caspase-8 and RIP3 were highly susceptible to bacterial infection, suggesting a key pathway for anti-bacterial defenses.

The article made it to the cover in the current issue of PNAS. Learn more about the image here.

Egil Lien. Foto: NTNU

Professor Egil Lien. Foto: NTNU

Reference

Wenga, D. , Marty-Roixa, R., Ganesana, S., Proulxb, M.K., Vladimera, G.I., Kaiserc, W.J., Mocarskic, E.S., Pouliota, K., Chand, F.K., Mellihere, M.A., Harrisf, P.A., Bertinf, J.,  Goughf, P. J., Shayakhmetovg, D.M., Goguenb, J.D., Fitzgeralda, K.A., Silvermana, N., Lien, E. Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death. PNAS (published online).

 

 

Leave a Comment

Filed under Infection, NTNUmedicine, Research

A new mechanism explaining the anti-inflammatory effect of HDL is revealed

 

espevik_fotografGeirMogen-(Nathalie_Niz_fotograGeirMog

Bloggers: Nathalie Niyonzima and Eivind Samstad

 

 

 

Atherosclerosis is a progressive disease that was once believed to be a disease of cholesterol storage. Today, it is well acknowledged that atherosclerosis is an inflammatory disease, and that cells and signalling molecules from the innate immune system shape the course of the disease in various ways. The defence of the normal artery depends on innate immune responses provided by endothelial cells. When challenged by inflammation, macrophages and other cells of the immune responses are recruited to the artery wall. The macrophage is an integral component to the pathogenesis of atherosclerosis, functioning at the intersection of inflammation and cholesterol homeostasis. Atherosclerotic plaque formation is driven by the persistence of lipid-laden macrophages in the artery wall. The mechanisms by which these cells become trapped, and thereby establishing chronic inflammation, remain unknown (Peter Libby, Nature 2011).

Atherosclerosis

Atherosclerosis. Illustration: iStock

There has long been a focus on finding therapeutic methods to reduce the levels of cholesterol in the arterial wall. Studies have shown that high HDL levels are associated with reduced cardiovascular risk. This is mainly due to HDL’s ability to transport excess cholesterol in arterial macrophages to the liver for excretion (i.e., reverse cholesterol transport). Despite considerable understanding of HDL and its metabolism, therapies that aim to increase HDL levels have not been successful. Because of the heterogeneity in HDL particles, just increasing HDL levels has not been beneficial, reflecting the qualitative changes in the particles. HDL has also been shown to have other functions beyond cholesterol transport – several studies have shown that HDL is anti-inflammatory, but the mechanisms behind this are not well understood (Xuewei Zhu, Ann.Rev.Nutr 2012).

In a recent study published in the prestigious journal Nature Immunology, our research partners have taken a closer look at the anti-inflammatory effects of HDL (De Nardo, et.al, Nature 2013). They identified that HDL’s anti-inflammatory effects are mediated through the induction of ATF3. ATF3 is a key transcriptional regulator of innate immune response genes, which is induced by TLR stimulation and other stimuli, and acts as negative regulator of proinflammatory cytokines (Elisabeth S.Gold, JEM 2012).

Using mouse model and human bone marrow dendritic cells (BMDMs) treated with native HDL or reconstituted HDL prior to TLR stimuli; they showed that HDL regulates inflammation in macrophages by inhibiting transcription of proinflammatory genes such as IL-1β, IL-6 and IL-12.

In order to confirm that the anti-inflammatory effects of HDL were mediated through an inflammatory repressor, they performed microarray analysis on resting BMDMs and HDL-pretreated BMDMs subsequently stimulated with TLR ligand. ATF3 was the most induced transcription factor in the presence of HDL, and it was shown to bind to the promoters of several proinflammatory genes, thereby regulating inflammation.

They demonstrated the relevance of these findings by using Apoe-deficient mice fed a high-fat diet and injected with HDL. They observed that mice treated with HDL had lesser inflammation than the untreated ones, and that the induction of ATF3 correlated with the downregulation of proinflammatory cytokines.

Besides promoting cholesterol efflux from macrophages, HDL has been shown to protect endothelial integrity by promoting endothelial repair mechanisms. Using a model of vascular repair, they showed that the protective effects of HDL on endothelial repair are for the most part driven by ATF3.

These results provide us a link between HDL and its anti-inflammatory properties that has been a puzzle over long time. The fact that ATF3 is required for the anti-inflammatory effects of HDL shows that ATF3 is a key point for endothelial damage and inflammation. The current study has laid the foundation for understanding the regulatory mechanisms that control inflammation in atherosclerosis and other chronic inflammatory diseases.

Leave a Comment

Filed under Inflammatory and Immune System, NTNUmedicine, Research

CEMIR recruits more researchers

Kari HålandBlogger: Kari Håland

 

 

 

 

Centre of Molecular Inflammation Research (CEMIR) keeps growing and is entering its second year with plans for increased research activity and more positions.

CEMIR was established on 1. January 2013 as part of the Research Council of Norway’s third round of Centres of Excellence (SFFs). CEMIR’s vision is to find out how sensors in the immune system initiates and regulates inflammatory responses. This new knowledge will be used in disease models to identify new therapeutic targets and diagnostic tools for inflammatory diseases.

Celleforskning. Foto: Geir Mogen

Trude Helen Flo with colleague Jane Awuh. (Photo: Geir Mogen)

This spring, CEMIR is recruiting for several research positions: 3 Post Docs, 2 PhD positions and 1 Staff Engineer. The Post Doc positions have now been announced.

“When CEMIR announced similar positions in 2013, we saw 220 applications,” says Director Terje Espevik. “This gives us a great opportunity to choose the best researchers and to find the most promising research talents.”

CEMIR moved into the new Kunnskapssenteret at Øya Campus in Trondheim in 2013. “We have excellent premises with plenty of room for our employees. The colocation of the centre gives us an excellent basis for establishing a unified milieu, and for cooperation and the exchange of ideas across the research groups,” Espevik says. “At the same time we remain close to the Department (the Department of Cancer Research and Molecular Medicine) in the neighbouring Gastrosenteret, which makes it easy to cooperate both organisationally and translationally.”

As part of becoming a centre, CEMIR has introduced several fixed meeting points bringing together the researchers at the centre. This includes weekly seminars and an article club where the aim is the share knowledge and to get feedback in terms of potential improvements or new research ideas from other colleagues at the centre. The SFF consist of research groups from various related subject fields, and there is no doubt that such close cooperation and exchange of ideas is beneficial.

“We look forward to having even more talented people that will contribute to the knowledge in our field. We constantly discover new research questions that we would like to explore further,” Espevik says.

A central question to CEMIR’s research is how inflammation can be so closely connected to many seemingly different chronic diseases. CEMIR’s research programme has a hypothesis that the key to new therapeutic targets for chronic inflammatory diseases can be found in the early stages of the inflammatory response where sensors in the innate immune system are activated.

The announced Post Docs are in the following areas:

  • Inflammation and Bone Disease. Project leader: Therese Standal, therese.standal@ntnu.no
  • Inflammation in Pregnancy. Project leader: Ann-Charlotte Iversen, ann-charlotte.iversen@ntnu.no
  • Host-pathogen Interactions in Mycobacterial Infection. Project leader: Trude Helen Flo, trude.flo@ntnu.no

Full job descriptions and more information can be found at the recruitment site Jobbnorge:

Leave a Comment

Filed under Inflammatory and Immune System, NTNUmedicine, Research

Looking for the perfect immune response

 

Blogger:Trude Helen Flo, co-director CEMIRtrude_helen_flo_FotografGei

The Research Council of Norway has recently awarded grants under the funding scheme Independent Basic Research Projects – Medicine, Health Sciences and Biology (FRIMEDBIO). There is tough competition for this funding nationally, and only the best projects get through. The Faculty of Medicine, NTNU, has been awarded funding for three talented young researchers, three research projects and two post docs. You can read about all these projects on the blog over the coming weeks. Trude Helen Flo and her colleagues at CEMIR were awarded funding to their research project: New Principles of mycobacterial killing in host macrophages (MycoHosPath).

Mycobacterial infections are a global health problem. Tuberculosis (TB) is caused by a bacterium known as Mycobacterium tuberculosis (Mtb) and kills more than 1.4 million people worldwide each year. Environmental mycobacteria like Mycobacterium avium can cause disease in immunocompromised people like HIV/AIDS patients who are not on anti-retroviral treatment. Mycobacterial infections require long treatment with antibiotics and drug resistance is emerging. Thus we need new drugs and vaccines in order to reach the UN millennium goal of eradication of tuberculosis.

To discover new therapeutic targets we need to learn more about the mycobacterium and how it interacts with its human host.

Tuberculosis

Mycobacterium tuberculosis (Mtb) and kills more than 1.4 million people worldwide each year

To discover new therapeutic targets we need to learn more about the mycobacterium and how it interacts with its human host.

Some major scientific and technological advances during the last decade have contributed significantly to progress in the field: studying the genetic makeup of mycobacteria provides clues about how the bacteria may infect and survive in the host. On the other hand, studying genetic variations in humans also provides insights in to how humans may become susceptible to mycobacterial infections.

Major breakthroughs in how our first line of defense, the innate immune response, can discriminate between different pathogens and shape the following second line of defense, the adaptive immune response, was awarded the 2011 Nobel Prize in Medicine. The adaptive immune response is crucial for the development of immunological memory. Despite these major advances, we still lack a complete understanding of mycobacterial immunity.

TB incidence rates and multidrug-resistant TB cases (click to enlarge image)

TBTB2

The primary research goal of the MycoHosPath project is to identify new principles of mycobacterial killing during acute and chronic infection. We will approach this by studying the interplay between three cellular pathways that are central for killing and intracellular survival of mycobacteria: Phagocytosis, Inflammatory signaling and Autophagy.

Untitled-1Phagocytosis is the process by which bacteria are taken up by innate immune cells like macrophages and dendritic cells. Normally this leads to destruction, but pathogenic mycobacteria have found ways to avoid it.

Autophagy is a similar process used by cells to detect and degrade garbage in their interior, including intracellular pathogens. Understanding how mycobacteria avoid these killing mechanisms and survive within macrophages may aid in discovery of new drug targets.

Inflammatory signaling is the macrophage response to infection. Infected macrophages produce potent molecules to alarm and recruit other immune cells to help clear the infection. Some of these molecules also help the infected cell to directly kill the invading micobes. However, since pathogenic mycobacteria can live in our body for a lifetime, this does not work perfectly. If we can improve our understanding on how a perfect immune response to mycobacteria should look like we could contribute to new vaccine strategies.

The combined processes of phagocytosis, autophagy and inflammatory signaling in host macrophages, and strategies used by the mycobacterium to manipulate them to its own advantage, will influence activation of mycobacterium-specific immune cells that we need to clear the infection and create immunity to further infection.

Our research group studies several of these aspects in the bacterium, in cells isolated from healthy and HIV-infected individuals, and in mouse model systems. As part of SFF-CEMIR we have access to national and international expertise on inflammation research and advanced imaging, state-of-the-art methodologies and new labs in Kunnskapssenteret.

We have also engaged strong national and US collaborators on autophagy and mycobacterial research who will contribute in what we hope will be a successful project. We are looking forward to realizing MycoHosPath next year.

Leave a Comment

Filed under Inflammatory and Immune System, Research