Aarhus Universitetshospital

Århus, Denmark

Aarhus Universitetshospital

Århus, Denmark
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Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.2.1.2-1 | Award Amount: 16.62M | Year: 2011

Colorectal cancer (CRC) is one of the most common cancers in both males and females, and it is perhaps the best understood of all epithelial tumors in terms of its molecular origin. Yet, despite large amount of work that has concentrated on understanding of colon tumorigenesis, we still do not know the full complement of molecular lesions that are individually necessary and together sufficient to cause colorectal cancer. Neither do we understand why some specific mutations that are relatively rare in other tumors (e.g. loss of the APC tumor suppressor) are extremely common in colorectal cancer. We propose here to use the tools of systems biology to develop a quantitative and comprehensive model of colorectal tumorigenesis. The model will include a wiring diagram that identifies cell-type specific and oncogenic pathways that contribute to colon tumorigenesis, and explains in molecular detail how a genotype of an individual CRC leads to activation of downstream genes that drive uncontrolled cell growth. This model will subsequently be used to find novel therapeutic targets, to guide genetic screening to identify individuals with elevated risk for developing CRC, and to classify patients into molecular subgroups to select the treatment combination which is optimal for each patient (personalized medicine). The specific objectives of the SYSCOL project are: 1. Identify genetic markers for individual risk using genotyping and sequencing of germline DNA from sporadic and familial CRC cases and controls 2. Identify genes and regulatory elements that contribute to colorectal cancer cell growth 3. Use data from Aims 1-2 to develop a quantitative model for colorectal tumorigenesis 4. Apply the model for identification of high-risk individuals, for molecular classification of the disease, and for identification of novel molecular treatment targets


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: KBBE.2013.2.2-03 | Award Amount: 7.95M | Year: 2013

Vitamin D deficiency has significant implications for human health and impacts on healthy growth and development and successful aging. Fundamental knowledge gaps are barriers to implementing a safe and effective public health strategy to prevent vitamin D deficiency and optimize status. ODIN will provide the evidence to prevent vitamin D deficiency in Europe and improve nutrition and public health through food. By establishing an internationally standardized analytical platform for 25OHD, ODIN will measure the distribution of circulating 25OHD and describe the prevalence of vitamin D deficiency in Europe. Using available biobanks and databases from National nutrition surveys ODIN will delineate the relative contributions of sun and dietary sources of vitamin D to circulating 25OHD. In support of planned EFSA revisions of vitamin D recommendations, ODIN will carry out three RCT in pregnant women, children and teenagers and a fourth RCT in ethnic immigrant groups to provide experimental data to specify vitamin D intake requirements. Using dietary modeling, innovative food-based solutions to increase vitamin D in the food supply through a combination of bio-fortification of meats, fish, eggs, mushrooms and yeast will be developed and ODIN will test the efficacy and safety of these products in food-based RCT varying in scale from small product-specific trials to a large total diet study in vulnerable indigenous and immigrant sub-groups. ODIN has assembled the largest critical mass of prospective adult, pregnancy and birth cohort studies to date and will conduct meta-analyses and individual subject-level meta-regression analyses to integrate standardized data on vitamin D status, a priori defined clinical endpoints and genotype to examine relationships between vitamin D and human health, including beneficial and adverse effects, on perinatal outcomes, bone growth and body composition and allergic disease in children and cardiovascular disease and mortality in adults.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-CSA-Infra-PP | Phase: INFRA-2010-2.2.7 | Award Amount: 6.99M | Year: 2010

Euro-BioImaging brings together imaging technologies stretching from basic biological imaging with advanced light microscopy, in vivo molecular imaging of single cells to animal models up to the clinical and epidemiological level of medical imaging of humans and populations. Euro-BioImaging, in close consultation with its stakeholders, will address the imaging requirements of both biological and medical imaging research communities by creating a coordinated and harmonized plan for infrastructure deployment in Europe. Euro-BioImaging infrastructures will be planned to provide access to state-of-the-art equipment as well as to provide training and continue the development of imaging technologies to be able to offer them as new services. The vision of Euro-BioImaging is to provide a clear path of access to imaging technologies for every biomedical scientist in Europe. The Euro-BioImaging infrastructure will be focused on imaging technologies grouped around different scales of biological organization, from the single molecule to the whole human organism. Euro-BioImaging will therefore develop a plan to construct and operate a set of complementary and strongly interlinked infrastructure facilities appropriately distributed across the European member states. To achieve this, Euro-BioImaging will define the legal and governance framework with its currently 22 member states and develop a finance plan in close cooperation with national funding bodies as well as with the European Commission. The key objective of the Euro-BioImaging preparatory phase project is to integrate these plans into an overarching business plan that provides a realistic basis for construction and operation of the Euro-BioImaging infrastructure. Through the combination of these technological and strategic objectives, Euro-BioImaging will be able to address the key elements of successful infrastructures: supporting research, training and innovation in biomedical imaging across Europe.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.1.3-2 | Award Amount: 7.79M | Year: 2014

Immune system response is the most complex barrier to long-term success of tissue transplants/implants from allogeneic and bio-artificial sources. While newly developed tissue transplant procedures are not yet performed frequently enough for robust analysis of adverse immune responses in humans, corneal transplantation (CT) is a well-established allogeneic tissue transplant with >100,000 full- and partial-thickness procedures performed annually. Adverse immune responses occur in up to 30% of CT recipients causing rejection and failure. The high levels of CT clinical activity and immune complications create an ideal opportunity to comprehensively profile immune responses associated with adverse tissue transplant outcomes and to develop new approaches for their prevention or early diagnosis. VISICORT is a multi-disciplinary project with expertise in basic immunology, bio-sampling, systems biology/immune profiling, bioinformatics, clinical tissue transplantation and cell therapy. It will complete the first systematic immune profiling of biological samples from animal and human CT recipients with diverse outcomes. Clinical data and bio-specimens from over 700 CT recipients at 5 leading transplant centres will be centrally collated and distributed to cutting-edge university- and SME-based laboratories for multi-platform profiling and integrated bioinformatics analyses. Profiling data will generate better understanding of adverse immune reactions to tissue transplants. This knowledge will be used to develop novel biomarker-based surveillance strategies and, coupled with SME-based expertise in cell product development, will also inform the design and initiation of an optimised clinical trial strategy of immunomodulatory stromal stem cell therapy in high-risk human CT recipients. VISICORT research will strongly impact multiple EU research/scientific communities, patient cohorts and SMEs and will have high commercialisation value for the biopharmaceutical and biotechnology industries.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2011.5.2 | Award Amount: 5.00M | Year: 2013

The past decade has seen a revolution in radiation therapy technology, offering exceptional flexibility in dose delivery. Image guidance during treatment ensures a reliable targeting of the dose to the tumor. This has created the possibility to irradiate the tumor with a high dose with minimal exposure of surrounding tissue. Thus an improvement in tumor control is no longer invariably associated with an increase in radiation-induced toxicity.\nNow, the capacity exists to create treatment plans that are tailored to the specific characteristics of the patient. Thus, the success of radiotherapy depends on proper personalized therapy planning and outcome prediction. However, an individualized representational model that informs on radiation therapy planning and outcome prediction is still lacking.\nThere are several modeling approaches available that have the potential to fill this gap, among them empirical, but established radiobiological models and more sophisticated multi-scale models.\nDR THERAPATs aim is to create the Digital Radiation Therapy Patient, integrating the available knowledge on tumor imaging, image analysis and interpretation, radiobiological models and radiation therapy planning into a reusable, multi-scale digital representation. DR THERAPAT will enable 1) Broad access to dose painting 2) Individualized planning resulting in more effective and safer treatment 3) Accurate prediction of Tumor Control Probability and Normal Tissue Complication Probability, 4) improve outcome, 5) provide a platform demonstrating the integration of modeling into the clinical workflow, and 6) provide a platform for the validation of the models.\nA demonstrator of this platform will be made for prostate cancer. With a second demonstrator for cervical cancer, we will show that the model can be translated to other forms of cancer. DR THERAPAT will adapt and integrate todays available tools into a digital representation of the patients health status and clinical workflow.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.96M | Year: 2016

Herpesviruses are widely spread, and cause life-long infections. Most individuals carry multiple herpesviruses, which can cause severe diseases, especially in children, immunocompromised individuals, and elderly. There are currently no safe vaccines against herpesvirus infections and current treatments are not satisfactory. With new insights into the molecular basis for diseases caused by immunodeficiency, and with the increasing numbers of elderly in Europe, there is now an unmet demand for improved treatments of herpesvirus infections. Combined with the progress in basic herpesvirus research, this calls for education of a new generation of scientists with strong research skills, advanced insights into disease mechanisms, and understanding of how industry brings innovative research into the market. In this application we propose an interactive education program for early stage researchers (ESR) in leading European laboratories, hospitals, and biotech companies. The focus will be on the virology and immunology of herpesvirus infections in the context of basic research as well as application of research-acquired knowledge. Our program will prepare the ESRs to manage goal-oriented interactions between academia, the clinics, and the biotech industry. The ESRs will acquire broad theoretical and methodological expertises involving several sectors to obtain the skills required for overcoming the cultural gaps From Bench to Bedside and From Discovery to Innovation. This can only be achieved through a network-based approach. We propose to develop a platform to educate the next generation of scientists to solve the outstanding problems in prevention and treatment of herpesvirus infections. The ESRs will be ideally trained to translate cutting-edge discoveries to novel products and to innovative treatment serving the European people, and hence to improve handling of present and emerging health challenges, as well as to foster the European biopharmaceutical industry sector.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-01-2014 | Award Amount: 5.98M | Year: 2015

Neuropathic pain (NP) is common (population prevalence of 7-8%) and will present a rising health burden in the future. NP results in significant morbidity, reduces quality of life and has a major deleterious impact on health in aging. The reason why some subjects develop neuropathic pain and others do not following the same injury is not known. The exact nature of risk factors for NP and their interaction are currently poorly understood and will be the focus of this project. We will establish an international consortium of leading researchers in the field of NP (DOLORisk consortium) involving members of established academic European consortia studying pain/genomics and neuropathy as well as the SMEs Neuroscience Technologies and Mentis Cura. The project will be highly translational and the starting point will be the study of patients with NP or at risk of developing NP. Specific objectives will be to: 1) Identify the influence of demographic factors, environmental/societal and clinical factors on the risk of developing and maintenance of NP 2) To apply modern genomics to validate (using a targeted approach) and find novel (using genome wide association) genetic risk factors for NP. 3) Use tissue samples and patient derived cells from Biobanks to validate of molecular pathways contributing to chronic pain in patients. 4) To determine if patient stratification using physiological (sensory profile, endogenous analgesic mechanisms and nerve excitability) and psychological factors can predict NP risk and progression. 5) Development of a risk model/algorithm for (severe) NP, combining measurable genetic and environmental factors. Our aim is to understand pain pathophysiology in terms of risk factors and protective mechanisms ranging from molecular pathways to societal impacts. The desired impact is to provide a firm platform to improve diagnosis and stratify patients according to risk profile, employ preventive strategies and ultimately develop novel therapeutics.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.2.4.2-1 | Award Amount: 16.05M | Year: 2011

WAKE-UP is an investigator-initiated, multicentre, randomised, double-blind, placebo-controlled trial designed to test efficacy and safety of MRI-based intravenous thrombolysis in patients with wake-up stroke. Every year 1.5 million patients suffer a stroke in the EU. Up to 20% of stroke patients wake up with stroke symptoms. Currently these patients are excluded from thrombolysis which is the only approved specific treatment available for acute stroke. However, recently the potential of MRI to identify patients likely to be within a time-window for thrombolysis (4.5 hours) was demonstrated. WAKE-UP will use a specific MRI pattern, i.e. the mismatch between a visible lesion on diffusion weighted imaging (DWI) and a normal fluid attenuated inversion recovery (FLAIR) image, to randomise patients waking up with stroke symptoms to either treatment with Alteplase or placebo. The primary endpoint will be favourable outcome at 3 months. A total of 800 patients will be enrolled in 40 centres in six EU countries. Additional MRI information such as vessel occlusion or perfusion lesion will not be used for enrolment but will be studied as possible modifiers of the response to thrombolysis. Software will be developed to facilitate the processing and analysis of multiparametric stroke MRI and to assist the integration of modern stroke imaging into acute treatment decisions. The trial will be accompanied by activities increasing the awareness for acute stroke in the public and results will be disseminated within the scientific community as well as within the public. WAKE-UP is aimed to promote a paradigm-change in acute stroke treatment, and to provide effective treatment to a large new group of patients. The results of WAKE-UP are expected to change guidelines of acute stroke management and clinical practice. WAKE-UP will help to reduce the burden of stroke related disability in the EU.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.4.2-2 | Award Amount: 3.83M | Year: 2011

Several studies have linked the use of insulins to the risk of cancer, and it is certainly plausible that as a growth factor, exposure to administered insulin could stimulate neoplastic growth. However, the meta-analyses of randomized clinical trials comparing different insulin analogues were too small to quantify the risks, especially the proportion of patients that were followed for more than 6 months. Hence, the European Medicines Agency has requested urgent research to determine the risks of cancer for users of insulin and insulin analogues, and investigate possible mechanisms of cancer promotion. CARING will obtain precise data on the incidence of cancer in diabetic patients and determine any link with use of various insulin and insulin analogues. The study will utilise high quality prescription databases and other national datasources, integrated at European level with advanced methods of harmonising data. The study will take into account potential confounders. The project aims to determine the influence of drug dose on risk, and through a risk model, identify predictors of cancer for insulin users. A review of published evidence combined with a study of tumour characteristics and gene expression in breast cancer tumour collections will aid understanding of potential mechanisms of cancer initiation and/or promotion by insulin. The project consortium involves some of the most experienced pharmacoepidemiology groups in Europe, and a leading cancer research institute. The consortium will liaise closely with the European Medicines Agency and other stakeholders throughout the study.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.77M | Year: 2013

The REtinal VAscular Modeling, Measurement And Diagnosis (REVAMMAD) project will train a new generation of scientists able to effectively translate the latest vascular modeling theory and computerized image analysis techniques into effective interventions for some of the most important chronic medic conditions afflicting the EU, including hypertension and diabetes. It will particularly ensure that there is rich clinical and industrial involvement to ensure that the training is focused with end-users and exploitation in mind. The vasculature undergoes changes in response to early stages of these diseases, reflecting fundamental physiological processes within the vessels. The retina provides a unique window onto the vasculature, allowing it to be viewed and measurements made in vivo, and advances in imaging technologies make it increasingly possible to measure subtle changes using computer vision algorithms, including through routine medical checks such as eye tests. The field is currently fragmented, with many excellent pockets of collaboration focused on defined specialisms, particularly between clinicians and modelers, or clinicians and measurement specialists, but lacking overall structure. Despite the importance and incidence of the diseases and the evidence for the possibility of better diagnosis through imaging, there has been relatively little translation of theory into clinical practice. Integrative action is required to train researchers who understand the medical, clinical, technological and commercial aspects of the problem domain and to establish common working methodologies and tools across the field. REVAMMAD will train early careers researchers who combine these skills in order to motivate the introduction of high impact interventions in the future.

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