Grants

Haematopoietic stem cell transplantation has the potential to cure malignant hematologic diseases. Unfortunately, up to 20% of the patients die from complications during the first year after transplantation. My project focuses on identifying risk factors for complications prior to and during transplantation. The project covers all patients receiving a transplant at Rigshospitalet, and the patients are closely monitored by analyses and biobanking of DNA, plasma and fecal samples. The project has four topics:

Parkinsons disease (PD) is a common, invalidating neurodegenerative disease caused by abnormal deposition of misfolded α-synuclein (α-syn) in neurons of the central and peripheral nervous systems causing neuron dysfunction and death. Up to 20 years before diagnosis, a-syn pathology can be found in the peripheral autonomic nerves including the skin and many patients develop neurogenic orthostatic hypotension (nOH) during the prodromal stage. Future neuroprotective treatments need to be started early to be most efficacious. The aim of this project is to improve our ability to diagnose PD early during the prodromal phase. We hypothesize that a significant proportion of patients with nOH are positive for α-syn pathology in skin biopsies, and have widespread asymptomatic involvement of the autonomic nervous system, therefore representing prodromal PD patients. We will follow such patients for up to five years to explore the rate at which they convert to manifest PD with motor symptoms.

Childhood maltreatment may be the most preventable risk factor for mental illness. Children are completely dependent upon care from adults, and can endure great hardship when properly tended for. But, when hardship is the product of their caretakers, and perhaps the ones that they need to be protected against, it creates a stressor with far reaching ramifications. The evidence is clear: Secure attachment to the primary caretakers is pivotal for developing secure relationships later in life. In adult psychiatry, exposure to childhood maltreatment may be much more common than expected and have a strong clinical impact. Neuroimaging studies suggest that indivduals exposed to maltreatment may have specific structural changes in the brain, and clnical studies suggest that maltreatment may emerge directly in the clinical picture many years later. Hence, it is important to investigate if maltreated individuals follow a different clinical course compared to non-maltreated individuals.

Bipolar disorder (BD) is one of the most important causes of disability worldwide. Due to the lack of objective tests, the diagnosis and assessment relies on clinical evaluations. The progressive development of BD is not prevented with the present treatment options. There is a rapid evolution of smartphone technology for remote monitoring. We developed a smartphone-based system for real-time symptom monitoring and collection of objective sensor data on behavioral activities. We propose two large scale smartphone-based studies in BD. In the observational BIO study patients with BD (n=400), healthy individuals at risk of BD (n=200) and healthy individuals (n=200) will be followed with smartphone data for a minimum of five years. In the SmartCAG trial patients with BD (n=900) will be randomized to using the smartphone-based monitoring system or standard-treatment. These studies will directly illuminate opportunities for identifying a smartphone-based composite marker and treatment in BD.

About 15% of breast cancer cases express the Human Epidermal Growth Factor Receptor 2 (HER2), which is associated with a poor prognosis. Antibodies directed against HER2 have significantly improved survival in HER2 positive breast cancer, but induce a risk of left ventricular dysfunction and heart failure. Regular imaging based evaluation of myocardial function is therefore recommended during HER2 directed therapy. This consists of a MUGA scan, which is associated with radiation exposure or rarely an echocardiogram. Both modalities are time and resource demanding and since biomarkers have been proposed as another modality in assessment of myocardial injury, the purpose of this study is to evaluate, if biomarkers can replace imaging based examinations of myocardial function during HER2 directed treatment. The study is a national multicenter, prospective randomized trial, where patients will be randomized to standard imaging monitored treatment or biomarker monitored treatment.

Klinefelter syndrome (KS) is the most frequent sex chromosome aneuploidy affecting about 85 to 250 per 100.000 liveborn males. Individuals with KS present with a variety of health problems and consequently are both morbidity and mortality rates increased. To date the genotype-phenotype relations in KS are still largely unexplained. Recently, we have presented data that point towards new mechanisms underlying the genetics of KS. Through earlier projects we have developed a unique clinical KS biobank supplemented by clinical data. The aim of this project is to further clarify the genetic basis for the phenotype seen. We will: 1) Characterize the epigenome and the transcriptome of phenotypically relevant tissues from adult patients with KS, 2) Identify genes, copy number variants and single nucleotid polymorphism that causally explain the KS phenotypes through integrative analysis of the molecular data and clinical data and 3) Evaluate candidate genes in a Zebrafish in modelling system.

Heart rhythm disorders comprise a spectrum of diseases ranging from benign self-limiting conditions to sudden cardiac death. Through four subprojects we will expand the existing knowledge on clinical, electrocardiographic and genetic aspects of human arrhythmia. The first subproject aims at describing the normal newborn's electrocardiogram during the first four weeks of life and generating reference values. The second subproject investigates the genetic components of inherited cardiac disease with focus on arrhythmogenic right ventricular cardiomyopathy and the novel familial ST-depression syndrome. The third subproject explores the heritability of various categories of sudden cardiac death and evaluates the diagnostic yield of family screening. Lastly, the fourth subproject is a Nordic initiative aimed at promoting precision medicine in cardiology. In conclusion, using a multifaceted approach, our data will provide novel insight into these conditions.

Vaccination of immunocompromised adults is critical in preventing morbidity and mortality related to infections. We will conduct epidemiological and clinical studies including two common and serious vaccine preventable infections in immunocompromised adults: pneumococcal disease and herpes zoster. We will explore incidence, complications, mortality and the potential benefit of vaccination through population based cohort studies using nationwide registers. A clinical study for evaluating a new Herpes Zoster Recombinant Vaccine will be conducted as a phase IV, open-label interventional trial. Liver transplant patients (40), Systemic Lupus Erythematosus (40), and immunocompetents (40) will be included. Pneumococcal vaccination will be given as standard of care. We will measure humoral and cellular immunity as primary and secondary outcomes and compare pre- and post-vaccination levels. Our results will support the development of vaccination guidelines for immunocompromised adults.

Multiphoton stimulated emission (MSE) was predicted theoretically shortly after the invention of the laser but has so far eluded experimental observation except in very exotic media. This changed by a discovery recently made in our group: the surprising appearance of MSE in a normal transparent piece of “glass” after its excitation by an ultrashort laser pulse. Normally, a dielectric material excited by a laser (pump) pulse exhibits metallic properties due to a high density of conduction-band electrons; a second (probe) pulse thus sees high reflectivity and strong absorption. However, under the right conditions, this behavior is replaced by strong amplification by MSE of the probe pulse. Time-resolved pump-probe measurements at Aarhus University and spectral-interferometry experiments at Universität Kassel on custom-made thin-film samples are combined with theoretical modeling with Technische Universität Kaiserslautern in order to investigate this new MSE amplification mechanism.

This project focuses on the impacts of sorting in the labor market. Sorting refers to the relationship between worker and firm heterogeneity in jobs. We study what drives the increasing sorting which have been documented previously and we test how sorting affects the productivity of firms. Increased sorting may affect both economic efficiency (by making firms more productive) and wage inequality (when firms share their productivity gains). A change in sorting, for instance due to technological progress that affects the allocation of workers to firms and leads to efficiency gains, may require policies to offset wage inequality. Designing such policies requires a quantification of what drives sorting and how sorting affects the economy. These two questions are therefore the core research questions of this research project.