From molecular understanding to improved disease treatment. Department of Molecular Medicine. University of Southern Denmark

Transcription

1 University of Southern Denmark From molecular understanding to improved disease treatment Department of Molecular Medicine RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE 1

2 Department of Molecular Medicine Winsløws Vej DK-5000 Odense C Tel The department builds bridges between the university, the clinically oriented environments at Odense University Hospital and other hospitals in Region Southern Denmark and Region Zealand through joint research projects, creating the framework for developing new methods for early diagnosis, monitoring and treatment. 2 RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE

3 PREFACE From molecular understanding to improved disease treatment The Department of Molecular Medicine at the Faculty of Health Sciences of the University of Southern Denmark (SDU) performs translational laboratory-based research with a focus on three research areas that reflect our three units: Cardiovascular and Renal Research Cancer and Inflammation Research Neurobiological Research Within the framework of these three units, the department creates value for society by generating an understanding of the human body s function and disease mechanisms, thereby contributing to improving human health. The research is carried out at a high international level and focuses, among other things, on the characteristics of the brain, immune system, circulation, kidneys, cancer cells and stem cells. Among the areas of strength where we stand out are the development of biological drugs, precision medicine for cancer and inflammatory diseases and mechanisms that cause neurodegenerative diseases, as well as renal diseases and hypertension. The research is of high quality and disseminated through prestigious international publications to the health care sector and broadly to society. The research is carried out in close cooperation with the clinically oriented environments at Odense University Hospital. This ensures that the department s efforts are relevant and benefit patients society. However, we also protect the individual researcher s freedom to carry out research and make room for talents with unique ideas which do not immediately appear to be directly application-oriented. We see ourselves as building bridges to the environments at the Faculty of Science with a more basic focus. The department teaches future doctors, chiropractors and other healthcare professionals basic biomedical subjects, including anatomy, neurobiology, physiology, pharmacology, immunology, molecular and cell biology, as well as microbiology. The Biomedical Laboratory is anchored in the Department of Molecular Medicine. The laboratory has a particular focus on the use of genetically modified mice, which creates an important foundation for innovative molecular and biomedical research at the department and the rest of SDU. At the same time, the laboratory works actively with sustainable use of laboratory animals by focusing on the three Rs: replacement, reduction and refinement. The Biomedical Laboratory contributes undergraduate as well as postgraduate teaching at SDU and Odense University Hospital. The Department of Molecular Medicine is a workplace with a focus on ethics and work environment in everyday life, and we aim to act holistically in a reliable and innovative environment. Uffe Holmskov Head of the Department of Molecular Medicine RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE 3

4 CANCER- AND INFLAMMATION RESEARCH Precision Medicine - breast and lung cancer Optimization of medical cancer treatment based on detailed molecular understanding of individual tumors is the main focus of our research. Today, categories of cancer patients are all offered the same treatment, despite the fact that nearly half of them will only suffer the side effects of the treatment without therapeutic benefit. In parallel, a number of new cancer treatments aimed at very specific molecular changes in cancer cells have been developed and many more are in preclinical development or being evaluated in clinical trials. These new drugs will benefit only those patients with cancers that have these specific changes. Therefore, there is a great need to clarify the molecular nature of the cancerous nodules to determine which medical treatment will be most optimal for a given cancer patient. Based on the results from analyses of DNA, RNA and protein from cancer cells, patients will be offered more individualized and targeted treatment. Our work focuses on three major therapeutic problems common to breast and lung cancer, the most frequently occurring cancers: Drug resistance Drug resistance is a serious clinical problem in cancer treatment since commonly used drugs that initially exhibit good effects may eventually lose their therapeutic effect. Our focus is endocrine resistance, wherein the effect of antihormonal therapy ceases. Using advanced molecular methods, we investigate the molecular mechanisms of the loss of effect of various antihormonal drugs that are normally very effective against hormone-sensitive breast cancer. We are also working to identify which new drugs can be added to antihormonal therapy to regain the therapeutic function against tumor growth. These studies are being performed in cell line models, animal models and examination of cancer tissue from patients. We have developed biomarkers that can assist in identifying specific treatments for individual patients. Recently, we identified CDK6 as a biomarker predictive of whether a patient will benefit from administration of a CDK4/6 inhibitor in addition to standard antihormonal treatment. Similar studies are being conducted on non-small cell lung carcinoma. Here, we are examining why the usually effective drug EGFR inhibitor loses its effect. In a new study, we have shown that patients with high pakt levels likely will benefit from an AKT inhibitor in addition to the EGFR inhibitor treatment. Circulating Biomarkers Biomarkers measured in blood are a new promising area that is the subject of intense work in our laboratory. In the blood, molecules (DNA, mirna and protein) that originate from cancer cells can be measured at a very early stage, and we have developed a 9-miRNA profile that can distinguish patients with very early breast cancer from healthy individuals. Such a test can eventually be used for screening studies. In addition, blood markers can determine if the patient is in danger of later recurrence of their cancer. We recently identified an amplification of a particular region of chromosome 1, which is detectable in blood samples from breast cancer patients, and found that patients with this amplification have a particularly high risk of recurrence. We have also determined why this amplification gives rise to a more aggressive disease course, and identified a new drug that is effective on this type of breast cancer. Immunotherapy Cancer Immunotherapy has proven to be very promising in recent years and is another area we are researching. We study the composition of tumor-infiltrating lymphocytes, an important prerequisite for effective immunotherapy. We are also investigating new immunosuppressive effects in cancer patients other than the most well-known ones. For example, data on the CD73 signaling pathway suggests that further blocking of immunosuppressive effects is essential to increase the number of cancer patients who will benefit from immunotherapy. Furthermore, we are studying a range of cancer-specific proteins, the so-called cancer/testis antigens, which can be used as valuable targets for immunotherapy. Our and other studies indicate two key factors: 1) upregulation of cancer/testis antigens in cancer cells renders them more susceptible to immunotherapy, and 2) the selection of the cancer/testis antigens, which have an important function in cancer cell survival, will be the most effective target for immunotherapy. In these immunotherapeutic studies, we focus on breast and lung cancer, melanoma, and brain cancer (glioblastoma). Contact: 4 RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE

5 There is a great need for clarifying the molecular nature of the cancerous nodules to determine which medical treatment will be most optimal for a given cancer patient. RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE 5

6 Many of our research projects are carried out in close collaboration with clinical departments in order to improve diagnosis and medical treatment of patients over time. 6 RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE

7 CANCER AND INFLAMMATION RESEARCH Inflammation and immune diseases The immune system protects us against the invasion of microorganisms such as bacteria, viruses and parasites. The system partly consists of the innate immune system and the acquired immune system. The latter has immunological memory that is activated when the immune system registers foreign biological material as present in all microorganisms. However, the immune system is not only activated during infections. It can also be activated in case of tissue damage and cancer, or when the immune system by mistake senses own tissue components as foreign leading to attack of the tissues by antibodies and immune cells. This is for instance seen in autoimmune diseases such as rheumatoid arthritis. In this disease and other autoimmune diseases that can occur in virtually any organ or tissue, a chronic inflammation state will develop leading to permanent tissue destruction as for instance seen in joints of patients with rheumatoid arthritis. Research In the laboratory, we use advanced cell biological and molecular biological methods to uncover unknown mechanisms and molecular players in the immune system both when it attacks microorganisms and when it is activated in autoimmune disease. Furthermore, there is a strong collaboration with industry and many foreign research groups. Examples of current projects: The development of immunosuppressant antibodies against infection in the retina of the eye The development of antibody conjugates with antibodies being used to prepare drugs for specific cell types in the treatment of inflammatory diseases and cancer. This type of precision medicine can significantly reduce dosage and side effects Blood proteins and the functions of cellular receptor proteins in the innate immune system, including the complement system The development of genetic engineering and other platforms for the development of new types of antibodies The study of the relationship between the immune system and other biological systems, such as the coagulation system The study of experimental models for inflammatory diseases in blood vessels, lungs, liver, and intestines. The research is mainly funded externally by public and private funds, such as Independent Research Fund Denmark, Innovation Fund Denmark, the Danish National Research Foundation, the Lundbeck Foundation and the Novo Nordisk Foundation. The new knowledge from studies in the laboratory is used in an innovative perspective to develop new diagnostic tools and medical therapy. In addition, we use the immune system s ability to make antibodies in order to produce antibodies that can be exploited as effective molecular tools in research, diagnostics and treatment. Contact: RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE 7

8 CANCER AND INFLAMMATION RESEARCH Inflammation research from molecule to patient Our inflammation research ranges from basic research to biomarker research in clinical materials and preclinical development of drugs; in other words, translational research covering the whole spectre from molecule to human being. What might begin with basic research in molecules can result in new ways to counteract and fight diseases such as hypertension, atherosclerosis and wear on the retina resulting in blindness. In basic biochemical research, we study different types of molecules and their particular characteristics and qualities. After that follows, step by step, research at the cell level, via animal testing and disease models as well as through clinical practice. The clinical studies are often carried out in collaboration with clinicians from Odense University Hospital, while studies using in-vitro or in-vivo models respectively in test tube and via animal testing are typically carried out locally in Winsløwparken, including at the Biomedical Laboratory. This is in addition to a number of international cooperation projects, primarily with European funding. Research into disease models Basic research aims at characterising molecular effects in the form of expression patterns, biochemical interactions and modulation of cellular activity. For a decade we have focused on molecules with certain structural similarities, including molecules with collectin structure or fibrinogen-related domains. The basic characterisation of molecules has mediated hypothesis-driven research in disease models and in miscellaneous clinically related issues. The current basic research primarily concerns diseases of the pulmonary (lungs and alveoli, which transfer gasses) or cardiovascular (heart and blood vessel) systems. In clinical trials, we are involved in research into lung diseases, including COPD (chronic obstructive pulmonary disease), asthma, allergies and lung fibrosis, as well as in rheumatological diseases and vascular diseases, including atherosclerosis, hypertension and pathological neovascularisation. Research into risk of COPD As examples of our current focus we can mention characterisation of the proteins SP-D and MFAP4. SP D is a molecule for pattern recognition with functions in innate immunity. Our basic research has shown that SP-D can have an immunosuppressant effect in the lungs. Among people at high risk for developing COPD, a greatly increased level of SP-D can be measured in the bloodstream. Therefore, it will be possible to register persons at high risk for developing COPD through a blood test, after which preventive initiatives and intensive treatment can begin. Preventing blindness With age, or as a consequence of diabetes, changes can occur in the retina, which in the worst-case scenario can lead to blindness. Some of the changes are caused by inflammation, which results in the ingrowth of small blood vessels on the retina socalled pathological neovascularisation. Our research has shown that the commonly occurring protein MFAP4 plays a detrimental role in this respect. Therefore, we research how to develop biological drugs aimed at MFAP4, which can block the harmful functions and counteract the development of blindness. Contact: 8 RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE

9 Basic research into molecules can result in new ways to counteract and fight diseases such as hypertension, atherosclerosis and blindness caused by age or diabetes. RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE 9

10 NEUROBIOLOGY RESEARCH Increased understanding of neurological disorders will lead to better treatment A large number of diseases affect the central nervous system, notably multiple sclerosis, Parkinson's disease, Alzheimer's disease, stroke, spinal cord injuries and various mental disorders such as schizophrenia. These diseases impact on the daily life of a very large number of people and therefore have high human and social costs. Researchers in the Neurobiology Research Unit examine the mechanisms underlying these diseases. Our goal is improved diagnosis and better treatment. To achieve this, we make use of animal models at the Biomedical Laboratory, brain cell and tissue cultures, as well as tissue samples from neurological patients, through collaboration with Odense University Hospital and other clinical centers. Contact: Alzheimer's disease Alzheimer's disease is the most common cause of dementia in the elderly. There is no effective treatment for the disease. Alzheimer's disease occurs due to a progressive loss of functioning nerve cells and their connections (synapses) in the cerebral cortex associated with deposition of various protein substances. This protein deposition leads to chronic brain inflammation. Our researchers investigate mechanisms underlying loss of nerve cells, including the role of chronic inflammation. We are investigating mechanisms underlying loss of synapses and nerve cells, including the role of chronic inflammation. 10 RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE

11 The goal is better diagnosis and treatment for Alzheimer s disease. RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE 11

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13 NEUROBIOLOGY RESEARCH Multiple sclerosis Multiple sclerosis is the most common cause of neurological disability among young adults and predominantly affects women. The cause of multiple sclerosis is unknown, current treatments are only effective at the early stages, and they cannot cure the disease. Multiple sclerosis and the related disease Neuromyelitis optica are thought to be autoimmune diseases, where the immune system attacks the nervous system. In the case of MS, this leads to destruction of myelin, which protects axons, and the axons themselves. We investigate immunological mechanisms underlying multiple sclerosis. We investigate immunological mechanisms of the disease, including how immune cells interact with the brain, and may in some cases help to repair the damage. Parkinson's disease Parkinson's disease is a common neurodegenerative disease, which primarily leads to the loss of dopamine-containing nerve cells at the top of the brain stem. The result is disabling movement disorders that may be accompanied by mental and cognitive changes. Motor symptoms caused by the disease can be treated medically, but after a relatively short time, the effect of treatment diminishes. We investigate disease mechanisms using patient-derived, induced pluripotent stem cells (ips cells) in our search for better treatment options. In addition, we investigate whether nerve cells which are lost can be replaced by transplantation of dopaminergic nerve cell precursors that are made from the nervous system's own repair cells, neural stem cells. We investigate disease mechanisms and search for better treatment options for Parkinson s disease. Spinal cord injury Spinal cord injury, e.g. after traffic accidents, is a disabling condition, often leaving the patient permanently paralyzed. There is no effective treatment for the paralysis or for the complications that occur after a spinal cord injury. Our research focuses on the possibility of limiting the loss of nerve cells and circuits immediately after damage has occurred, and on improving the possibility for repair and restoration of nerve pathways. Peripheral nerve damage also affects many of these trauma patients. To repair peripheral nerves, we use the patient's own cells in connection with biomaterials. Our research could lead to better treatment and rehabilitation of patients with these injuries. Our research could lead to better treatment and rehabilitation of patients with spinal cord injury. RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE 13

14 NEUROBIOLOGY RESEARCH Stem cell therapy in the nervous system Stem cell therapy is a prospective future treatment strategy for diseases and injuries in both the central and peripheral nervous systems. For successful treatment, it is important that the cells used are not rejected and do not harm the patients. We work to produce and characterize stem cells from the patients' own tissues, in order to reduce the risk of tissue rejection and the need for immunosuppressive drugs. In addition, we work on characterization of bone marrow cells and we study their immunomodulatory properties in the central nervous system. We are working to produce stem cells from patients' own tissues to reduce the risk of tissue rejection and the need for immunosuppression. Stroke Stroke, due to a blood clot or cerebral hemorrhage, is one of the most common causes of death in the western world, and frequently leaves survivors with consequences such as paralysis, speech deficits and memory loss. We investigate interaction between the brain and cells of the immune system, which enter the brain after a stroke. Our goal is to identify mechanisms that affect the survival of brain cells, especially neurons, in and around the damaged areas. We investigate the impact of various drugs and cell therapies. Our research focuses on reducing brain damage for better rehabilitation of stroke patients. Our research focuses on reduction of brain damage for better rehabilitation of stroke patients. 14 RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE

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16 Our research has shown that lives can be saved by introducing a screening program for older men. 16 RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE

17 CARDIOVASCULAR AND RENAL RESEARCH Atherosclerosis, aneurysms and diabetic complications Around 300,000 Danes suffer from diabetes, and roughly the same number is estimated to have a precursor for diabetes. Diabetes causes damage to large blood vessels and small blood vessels in the kidneys and eyes. Diabetes affects the development of atherosclerosis and bulges on the main artery (aneurysms) common diseases that develop slowly and often without symptoms. They can lead to a blood clot in the heart or brain or rupture of the main artery, causing death as well as damage to the heart and kidneys. Among the risk factors are a fat rich diet, lack of exercise, smoking and hypertension. The risk of acquiring these sequelae increases, the more poorly blood sugar and blood pressure are regulated. Our skeletal muscles play an important role in regulating our blood sugar. A reduced sensitivity to the hormone insulin in the skeletal muscles is associated with an increased level of glucose in the blood, thus increasing the risk of coronary disease. Diabetes The scientists at Cardiovascular and Renal Research focus on studying the molecular mechanisms that lead to reduced sensitivity to insulin also known as insulin resistance in the skeletal muscles of patients with type 2 diabetes. Among other things, we study how exercise and the male sex hormone testosterone affect the function of the muscle cells. Diabetes increases the occurrence of atherosclerosis. Atherosclerosis in the arteries causes a gradual restriction of the blood vessel, such as when fat is embedded, which leads to inflammation of the vessel wall. We examine how diabetes and atherosclerosis cause changes in the structure and function of the blood vessels. Here there is a special focus on changes in extracellular matrix proteins and basement membrane composition. These are both part of the blood vessels skeleton and contribute to the stability and functioning of the blood vessel. models, where it is genetically possible to disable genes either in the entire mouse or in specific cells or organs. Aortic aneurysms Unlike atherosclerosis, the changes in the vessel wall which can be seen in diabetes protect against the development of bulges on the main artery, so-called aortic aneurysms. Aortic aneurysms affect around 6% of all men over the age of 65. This is a disease that is often not detected until the aneurysm has become large enough for the main artery to burst often causing death. Researchers at Cardiovascular and Renal Research have shown that lives can be saved by introducing screening programmes for older men. Even if these bulges on the main artery are discovered, no medical treatment for reducing their growth exists today. Patients are systematically monitored until the bulges have become large enough for the risk of rupture to be greater than the risk of an operation where prostheses are inserted on the inside of the blood vessel. Our researchers focus on changes in the structure of blood vessels that can contribute to the growth, as well as to the weakening, of the blood vessel. Here there is a special focus on the immune system, on methods for preserving the elastic fibres in the blood vessel wall, thereby reducing the weakening of the blood vessel, as well as on the contribution from small blood clots on the inside of the vessel wall. The long-term goal is to develop a medical treatment and make it easier for doctors to decide when surgery should be offered to this patient group. All the studies have the common aim of obtaining a greater understanding of the development of these diseases to ensure a more targeted treatment that can improve patients life quality. Contact: As something completely unique, the analyses are carried out on blood vessels from a biobank to which patients have generously donated small pieces of blood vessels collected during surgery. These studies are supported by experimental mouse RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE 17

18 CARDIOVASCULAR AND RENAL RESEARCH Renal disease, transplantation and kidney function Kidneys are vital organs which excrete waste materials, stimulate the creation of red blood cells, regulate the body s salt and water balance, and determine blood pressure. Therefore, it has a great impact on the body if kidney function is reduced because of illness. Some of the most common reasons for permanent renal impairment are diabetes and high blood pressure (hypertension). Both in Denmark and globally, the number of patients suffering from renal diseases is growing. Today, around 10% of the population suffers from some level of renal impairment. In long-term renal disease, there is a risk that the damage to the kidneys is widespread enough to stop them from functioning. In that case, dialysis or a kidney transplant are the only possible treatments. How is it possible to monitor the functioning of a transplanted kidney? How does immunosuppressant treatment impact the functioning of a transplanted kidney? How is it possible to predict the rejection of a transplanted kidney? The questions are analysed at many levels in order to obtain the most in-depth knowledge. Therefore, cultured cells from the kidneys, experimental animal models of various renal diseases and samples collected from patients suffering from renal diseases in Region Southern Denmark are used. As something unique, kidney tissue collected from patients suffering from renal cancer is also used. We are looking for answers There is therefore a great need to understand the causes of chronic, progressive renal disease and how damage to the kidneys occurs. Therefore, we are working on finding the answers to a number of questions: Why do kidneys become leaky and leak protein into the urine? What causes hypertension and kidney damage when protein is leaked into the urine? What is the reason for the kidneys to hold back salt and water in the organism? How do the kidneys regulate the body s balancing of different minerals (Na+, K+ Mg2+, Ca2+)? How is scar tissue created in the kidneys? The purpose is to bring the research as close to the patients as possible so that it is easier to transfer positive results to daily clinical practice. This is supported through close cooperation between the University of Southern Denmark, Odense University Hospital and other hospitals in Region Southern Denmark. In addition, several employees in the projects are employed in positions affiliated with several of the institutions involved. The purpose of the research is to gain greater insight into disease mechanisms among patients suffering from renal disease and thereby develop new methods for diagnosis, treatment and treatment monitoring. Contact: 18 RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE

19 There is a great need for understanding the causes of chronic, progressive renal diseases and how damage to the kidneys occurs. RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE 19

20 20 RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE In our research, we focus on prevention, treatment and repair of organ damage.

21 CARDIOVASCULAR AND RENAL RESEARCH Heart, blood vessels, blood flow and blood pressure Cardiovascular diseases are still the main cause of death among men and women. In Denmark, about 1 million people suffer from high blood pressure (hypertension) and 300,000 of them are not aware of it. This can be a consequence of diabetes and cause organ damage in many places in the body, including the brain, eyes, heart and kidneys. Blood pressure and hypertension are determined by the heart, the blood vessels and the body s salt balance. In our research, we focus on prevention, treatment and repair of organ damage. Hypertension and diabetes are common in Denmark. They cause morbidity and mortality from heart diseases, blood clots in the brain, peripheral vascular disease or renal insufficiency. Our research With a focus on heart and blood vessels, researchers at Cardiovascular and Renal Research therefore study: How increased blood pressure or sugar levels change the structure and function of blood vessels, How these changes can be prevented through exercise or counteracted by drugs, and How damage to the brain can be repaired and new blood vessels constructed. We focus particularly on signalling molecules, produced locally or for the whole organism as hormones, and how these change the structure of the cardiovascular system and modulate cell function in the heart, blood vessels and tissues. In collaboration with Odense University Hospital, we use a biobank in our research to which patients have donated small pieces of blood vessels collected during surgery. In this way, it is possible for the first time to test hypotheses related to the causes of hypertension, complications of diabetes or drug effects in blood vessels from patients. In addition, we use isolated cells, intact animals (mice and rats) as well as volunteer subjects and patients in our studies. For instance, we isolate cells that can help regenerate tissue. In other studies, we measure the blood flow through the skeletal muscle in the subjects thigh to help us understand how circulating and local hormones work. In collaboration with the Faculty of Science, we use new imaging techniques with increased spatial and temporal resolution. The studies are often carried out across the department with colleagues focusing on major artery diseases such as atherosclerosis and aneurysms, or on renal function and renal failure, and in collaboration with colleagues at the Centre for Individualised Medicine in Arterial Diseases at Odense University Hospital. Contact: RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE 21

22 BIOMEDICAL LABORATORY Animals give researchers direction Animal research is indispensable in biomedical research, as not all conditions can be investigated in isolated cells (in-vitro research) and it is not acceptable to test new treatment methods in patients without knowing their possible effects, wanted as well as unwanted. the study of human genes in transgenic mice, or investigation of the effects of the absence of one or more genes in so-called knock-out mice. Both techniques are very important for the research which is in focus at the Department of Molecular Medicine. For research purposes, where in-vitro research cannot be used, because of the need for interaction between different cells, the influence of blood pressure, or neurotransmitters in the intact brain, it is necessary to use animal experiments. Current knowledge of the human body's physiology and pathology is largely based upon animal experiments. Experimental animals are therefore good models for studying the human body's functioning and diseases. The most commonly used animals in research are mice and rats. In Denmark, approx. one quarter million experimental animals are used, of which 60% are mice and 20% are rats. At the Biomedical Laboratory, most of the animals housed for research purposes are mice. The population consists of approx. 6,500 mice and 200 rats. Compared to the national average, relatively few rats are used at the Biomedical Laboratory. Mice are used for virtually all research areas where the influence of genetics plays a role, because mice can easily be genetically modified and reproduce fast. Therefore, mice are very useful for gene-based research. Genetic engineering research allows The staff of the Biomedical Laboratory is highly specialized in the care of experimental animals, and the wellbeing of the animals is paramount. Animals can only be used for research purposes if they do not suffer from the experiments, and the animal care takers, with their experience, assess whether the animals thrive. The staff of the Biomedical Laboratory has a close dialog with researchers on animal welfare and can also assist in experiments, for example with dosing or blood sampling. Additionally, an animal welfare body is established at the Biomedical Laboratory, which is a forum where animal welfare aspects of animal testing, measures that improve animal wellbeing and possible alternatives to animal testing are discussed. Apart from the necessary licenses for animal research projects from the Danish Animal Experiments Inspectorate, researchers must be qualified to participate in animal experiments. The Biomedical Laboratory offers courses in obtaining such a qualification. Contact: 22 RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE

23 The majority of these animals are used for research in brain disease, cancer or cardiovascular disease serious diseases that we all want to prevent or cure. RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE 23

24 Department of Molecular Medicine Winsløws Vej DK-5000 Odense C Tel RESEARCH REPORT, DEPARTMENT OF MOLECULAR MEDICINE