Nicolai Albrechtsen

Individuals with diabetes are at risk of developing dementia. Both diseases contribute to impaired quality of life and poses and an economical cost on our society. Insulin and glucagon are two hormones from the pancreas that play a key role in the development of type 2 diabetes. Recently, insulin has been shown also to contribute to dementia. The role of glucagon in brain metabolism and its potential link to dementia is unknown. In this proposal, we will determine the potential actions of glucagon in the brain through series of investigations and extensive state-of the art techniques in rodents, healthy individuals, and patients with type 2 diabetes. The findings obtained in these proposed investigations may reposition the role of glucagon as a peripheral hormone to also be a central regulator of brain metabolism in health and disease. Glucagon-based medicine may thereby be of clinical importance for the patient with type 2 diabetes at risk of dementia.

Lykke Sylow

Our muscles play a crucial role in our daily life, health, and overall well-being. As we age, there is a natural decline in muscle function, and certain diseases like diabetes and cancer can make it worse. To make sure our muscles stay healthy and function properly, they require certain proteins. These proteins play a crucial role in producing energy and regulating the amount of glucose (sugar) in muscle. This research project aims to understand how these proteins are made and how factors like exercise, inactivity, or obesity affect this process. By gaining insights into these mechanisms, we hope to enhance treatments for age- and disease-related muscle issues, ultimately improving quality of life.

Lars Rolighed

Lars Rolighed says: “The general metabolism is partially regulated by the thyroid gland. In health and disease, thyroid hormones help to stimulate bodily mechanisms in the right way. Commonly, the thyroid gland is affected by various diseases and occasionally surgical treatment is needed. In Denmark, the most common operative procedure on the thyroid gland is a hemi thyroidectomy with removal of half of the gland. This operation often reduces the thyroid hormones to a degree where the metabolism is negatively affected. Accordingly, many patients with a previous neck operation need to take medication daily for the rest of their life. With many different thyroid diseases, there are several treatment options. We will evaluate new management options in clinical prospective studies. These new options include 1) use of active surveillance of small tumors and 2) radiofrequency ablation of small thyroid tumors. Further, in a national 20-year cohort, we will retrospectively evaluate long-term adverse outcome after hemi thyroidectomy. Finally, we will perform molecular profiling of thyroid tumors including circulating tumor DNA and describe essential mutations for development of cancer and disseminating disease. With this project, we aim to improve outcome for Danish thyroid patients with possible beneficial impact on long-term health outcomes.”

Lars Rolighed is Consultant Surgeon at Department of Otorhinolaryngology and Department of Surgery, Aarhus University Hospital, and Associate Professor, Department of Otorhinolaryngology, Aarhus University Hospital, since 2016.

Anne Hammer Lauridsen

Anne Hammer Lauridsen says: “Globally, 8.6% of all female cancers can be attributed to human papillomavirus (HPV). The purpose of this project is to explore the underlying mechanisms for why HPV causes the development of cancer in some women, but not in all those infected with the virus. A better understanding of the molecular mechanisms in the development of HPV-related disease of the cervix may enable an identification of novel biomarkers applicable to screening, clinical management, and treatment, thereby potentially reducing risk of under- and overtreatment. In the proposed project, we will use tissue samples from women with premalignant cervical lesions and women with cervical cancer. To explore the molecular mechanisms, we will perform state-of-the-art molecular analyses, including mutation analysis and an analysis of the women’s immune response to the virus. Results from the proposed project will be important not only for our understanding of HPV-related cervical disease, but also for other HPV-related diseases.”

Anne Hammer Lauridsen is Senior Consultant and Head of Research at Department of Obstetrics and Gynecology, Gødstrup Hospital. Anne Hammer Lauridsen has been Clinical Associate Professor at Department of Clinical Medicine, Aarhus University, since 2022.

Henrik Schytz

Henrik Schytz says: “Spontaneous intracranial hypotension (SIH) is a serious and underdiagnosed brain disease characterized by low cerebrospinal fluid (CSF) pressure caused by a leak in the membranes surrounding the brain and spinal cord. In SIH, brain function is severely affected, leading to cognitive dysfunction and severe headache when standing up. The current study will investigate 500 patients suspected of SIH with state-of-the-art diagnostic tests and imaging methods to diagnose and predict the outcome of SIH. The study will also investigate SIH patients before and after treatment in comparison to healthy controls using advanced 7 Tesla magnetic resonance imaging (7T MRI). The 7T MRI studies will demonstrate how SIH affects brain regions that control CSF flow and clearance of brain waste products. The study will lead to new knowledge and methods on how brain function is affected by changes in intracranial pressure, which can be applied in many other neurological conditions.”

Henrik Schytz is Consultant in Neurology, Danish Headache Center, Rigshospitalet-Glostrup, and leader of the Headache Diagnostic Laboratory, Danish Headache Center. Henrik Schytz has been Associate Professor at Department of Clinical Medicine at University of Copenhagen since 2016.

Nina Kimer

Nina Kimer says: “Alcohol-related liver cirrhosis has immense impact on patient’s health. Only half of patients are alive two years after diagnosis. Treatment of cirrhosis is directed at complications and symptom-relief, and only few trials have explored actual effects of removing the causal factor, the alcohol, on the liver function. In clinical studies we will induce alcohol-cessation and investigate the effects on liver function and the recovery from complications, defined as recompensation. We believe recompensation will improve survival markedly. We will also investigate the effects of alcohol-cessation on the liver function by performing protein, lipid and gene activation analyses on liver cells. The studies may also lead to new discoveries of mechanisms that may heal liver tissue and restore the functions of the liver.”

Nina Kimer is Medical Specialist in gastroenterology and hepatology at the Gastro Unit, Amager-Hvidovre Hospital.

Liselotte Vogdrup Petersen

Liselotte V. Petersen says: “The overarching purpose is to optimize estimation in case-cohort samples and explore genetic pathways using information from Danish registers. The case-cohort sampling design has several advantages compared to other sampling designs as the control group can be reused to study other case groups and absolute measures such as percentages (and the certainty of the percentage) can be estimated. However, this is not covered in standard statistical packages for scenarios such as competing risk. Therefore, we will explore the possibilities and provide recommendations to optimize estimations in case-cohort studies, including time to event data in genome-wide association studies. We also aim to find subgroups of cases that have distinct biological pathways to disease by utilizing register-based information on exposures in various case-only genome-wide association studies.”

Nicolai Birkbak

Nicolai Birkbak says: “The aim of this project is to unravel the mysteries of how our immune system changes as we age and how these changes influence our overall health. Using cutting-edge technology, we will delve into the intricacies of individual cells from thousands of people, with a particular focus on understanding how age and biological sex impact the immune system. Our goal is to develop innovative methods and apply advanced artificial intelligence tools to accurately measure the health and state of the immune system and demonstrate how immune health relates to general health and particularly to cancer development and outcome. This knowledge holds the potential to transform how we view the relevance of immune health. Potentially, it could pave the way for new immune-boosting strategies to prevent and treat various age-related diseases, offering a brighter and healthier future for individuals as they grow older.”

Marco Donia

Marco Donia says: “Immunotherapy works by re-activating the body’s immune system to recognize and eliminate cancer. Some patients with advanced cancers, including melanoma, lung, and renal cancer, can be cured by current immunotherapies. However, most patients whose cancers initially regress after immunotherapy become resistant and grow back again. The determinants leading to this “acquired resistance to immunotherapy (ARI)” are unknown. Consequently, there is no curative treatment for patients who develop ARI. This project will pinpoint the genes and molecules responsible for ARI. Based on clinical data, we will generate complex high-throughput preclinical models to reproduce and study the molecular determinants behind immune evasion. These models will then be used to test therapeutic strategies against resistant cancers. These works will pave the way for new potential treatments for patients with ARI.”

Marco Donia is Staff Oncologist at the Department of Oncology, National Center for Cancer Immune Therapy (CCIT-DK), Copenhagen University Hospital (Herlev and Gentofte), and Associate Professor, Department of Clinical Medicine, University of Copenhagen, since 2017.

Anne Skakkebæk

Anne Skakkebæk says: “Sex chromosome aneuploidies (SCAs) are conditions where females or males have an abnormal number of sex chromosomes, like Turner syndrome (45,X) and Klinefelter syndrome (47,XXY). Patients with SCAs suffers from a range of diseases (congenital malformations, infertility, diabetes, cardiovascular diseases, psychiatric diseases). The fetal period and early childhood are critical periods with complex mechanisms regulating the activity of our genes being founded. These mechanisms have profound impact on health and disease. Our hypothesis is that altered dosage of sex chromosomes disrupt these mechanisms in the fetus and child with SCA, leading to the increased disease burden thorough out life. We will examine these mechanisms in tissues from aborted fetuses with SCAs, and in tissue samples from children with SCAs and control fetuses and control children. In addition, we will measure health outcome and other clinical measurements of the fetuses and children to answering the fundamental biological question how altered sex chromosome number leads to an increased diseases burden in SCAs.”

Anne Skakkebæk is medical geneticist at the Department of Clinical Genetics, Aarhus University Hospital, and Clinical Associate Professor at Department of Clinical Medicine, Aarhus University, since 2021.