Anniek Lubberding

Type 2 diabetes occurs when secretion of insulin does not meet the body’s demands. Insulin secretion is dependent on ion channels, which transport ions across the cell membrane. People with mutations in an ion channel called Kv11.1 have increased insulin secretion, but I recently identified that insulin secretion is only increased if the mutation lies in a specific part of the channel: the so-called PAS domain. This domain does not transport ions, but is responsible for contact with other proteins, potentially proteins involved in the secretion of insulin. The aim of this project is to investigate the role of the PAS domain in insulin secretion and blood sugar control by developing a new, state-of-the-art mouse model, using several human databases and a small clinical trial, and testing novel pharmacology. As such, this project will highlight unconventional roles of ion channels previously unrecognized and will provide the first steps to a new treatment strategy in diabetes.

Grethe Ueland

Benign adrenal tumors are common and affecting approximately 5% of the adult population. 30-50% of the cases shows overproduction of the stress hormone cortisol, a condition named mild autonomous cortisol secretion (MACS). MACS is associated with hypertension, type 2 diabetes, obesity and unfavorable cholesterol profile, conditions that gives increased risk of developing cardiovascular disease. Diagnosing MACS is troublesome, and easy screening test are lacking. The impact on the body of living with untreated MACS is also unknown.  Furthermore, what is the optimal treatment is debated, conservative approach to the comorbidities or surgery of the adrenal gland. Our aim is to close these knowledge gaps through establishment of evidence-based international guidelines for diagnostics and treatment of MACS, and to get a deeper insight into the inflammatory impact of this disease.

Diego Balboa

Diabetes is an alarming global health problem that requires innovative therapeutic solutions. Current treatments fall short, as they do not resolve the primary disease mechanisms behind impaired insulin secretion. Recent advances in stem cell technology make possible the generation of insulin-secreting cells in the lab. However, these stem cell-derived cells are immature due to our limited understanding of how they fully develop naturally. The aim of this project is to gain insights into the mechanisms that orchestrate islet cell maturation by combining data generated with state-of-the-art technologies, including stem cell models, single-cell analytics and editing of the genetic code. This novel information will help us to test how to improve the generation of stem cell-derived insulin-secreting cells for therapy and disease modeling, translating into better diagnostic and treatment tools for diabetes.

Niels Banhos Danneskiold-Samsøe

Peptide hormones are small strings of amino acids that are crucial for regulating our metabolism. Drugs derived from peptide hormones are used in the treatment of metabolic disorders including obesity and diabetes. Peptide hormones are cleaved from larger precursor proteins at specific amino acids. Using this knowledge uncovered a novel peptide hormone. The project aims to determine what regulates the release of this peptide hormone, which cells that produces it, and what role it plays in metabolism.

Given the importance of peptide hormones in health and disease, genetic mutations affecting peptide hormones are often harmful. The project utilizes an algorithm based on prediction of how likely a potential peptide is to cause harm, and where peptides are cleaved in proteins, to identify potential novel hormones and explore their effects on metabolism.

Pim Van Den Hoven

Pim Van Den Hoven says: “Patients with diabetes are at risk of developing a wound on their foot called a diabetic foot ulcer (DFU). Up to one in every three patients with diabetes will develop a DFU in their lifetime. Despite treatment, the DFU will not heal in up to thirty percent, leading to a high risk of amputation. One of the main reasons a DFU does not heal is decreased perfusion to the foot. Currently, the medical field lacks a tool to measure this foot perfusion in a reliable way. To improve outcome in DFU diagnosis and treatment, there is urgent need for a better way to assess this perfusion. The PODO-MAP project examines three potential imaging techniques to fill this gap: advanced duplex ultrasound, contrast enhanced ultrasound and near-infrared fluorescence imaging with indocyanine green. Also, a clinical registry is performed for patients with a DFU to gain insight in the clinical. By doing this, we aim to improve outcome by increasing the healing rate and reduce the amount of leg amputations.”

Pim Van Den Hoven has a longstanding interest in vascular surgery and is currently doing his specialist training at Department of Vascular Surgery, Rigshospitalet, and Leiden University Medical Center, The Netherlands. He further says: “The Clinical Emerging Investigator Fellowship from the Novo Nordisk Foundation will be instrumental in establishing myself as research leader within the field of near-infrared fluorescence imaging”.

Inger Lise Gade

Inger Lise Gade says: “The air we exhale is a highly accessible yet unexploited biological sample that can be collected non-invasively. This project aims to revolutionize disease diagnosis and monitoring by harnessing the untapped potential of exhaled breath analysis. Using pulmonary embolism and stroke as examples, this project ultimately seeks to shift the diagnostic paradigm towards non-invasive, point-of-care analysis based on exhaled breath to start already in the pre-hospital setting. The project will for the first time combine proteomic and metabolomic analysis of exhaled breath to advance the understanding of the acute cellular and biological mechanisms in pulmonary embolism and stroke, respectively, thereby aiding identification and validation of novel exhaled biomarkers suitable for point-of-care testing. The specific activities in the project encompass a literature review study on proteomic and metabolomic analysis to establish a protocol for exhaled breath sample collection and omics-analysis. The protocol will be tested in a methodological study before application in subsequent pre-clinical and clinical studies of stroke and pulmonary embolism. Reproducible porcine model of hemorrhagic and ischemic stroke variants will be developed. A paired porcine study of stoke will provide optimal conditions for identification of exhaled biomarkers able to discriminate the different types of strokes. Clinical studies of exhaled biomarkers for pulmonary embolism and stroke will validate the identified putative new, exhaled biomarkers and be the cornerstone for futures new, non-invasive exhaled breath tests.”

Inger Lise Gade has a longstanding interest in looking for biomarkers in exhaled breath and is currently doing her specialist training in Internal Medicine at the Department of Hematology, Aalborg University Hospital. She says: “The Clinical Emerging Investigator grant will permit me to combine my clinical and research training and allow me to establish my own research group and take a unique international first-mover position in the cutting-edge research field of exhaled breath.”

Kristian Kragholm

Kristian Kragholm says: “The electrocardiogram (ECG), a low-cost and readily available test of the heart’s electrical system, holds promise to improve detection of critical conditions in the prehospital setting to improve outcomes. We propose a shift to a broader inclusion of ECG abnormalities, symptoms, and vital signs including blood pressure, blood oxygen levels, heart and breathing rates, to indicate a significant blood clot in the heart’s artery system that requires balloon stenting. A similar approach will be used to examine pulmonary artery clots, aortic dissection (an acute tear in the wall of the major artery, the aorta), and acute heart failure. Finally, we propose to use ECG information to predict cardiac arrest. The outlined projects build on a nationwide Danish ECG cohort and linkage to national registries, with potentials for guiding future artificial intelligence applications that can aid clinicians in early detection of the critical, life-threatening conditions to improve patient outcome.”

Kristian Kragholm is currently doing his specialist training in Cardiology at the Departments of Cardiology at North Denmark Regional Hospital, Hjørring, and Aalborg University Hospital. He has been Associate Professor at Department of Clinical Medicine, Aalborg University, since 2022. Kristian Kragholm further states: “This funding will consolidate me as an independent research leader and allow me to continue doing research that I believe will have a huge impact on care and outcomes of patients with acute cardiovascular conditions in the pre- and in-hospital setting and will consolidate me as an independent research leader.”

Jakob Werner Hansen

Jakob Werner Hansen says: “VEXAS is a newly discovered disease first described in December 2020. It is caused by an acquired mutation in the UBA1 gene in the hematopoietic stem cells. The mutation is found on the X-chromosome, so it is primarily elderly male individuals which are diagnosed with the disease. The syndrome is characterized by autoimmune symptoms, such as fever, skin rash and cytopenia which are debilitating for the patients and affecting both quality of life and affects overall survival. This proposal outlines our plan to conduct a clinical trial in the Nordic countries using the promising drug (azacitidine), which is not currently approved for the treatment of these patients. Furthermore, we will investigate the cells from the blood and bone marrow to get a better understanding of the disease, this combined effort will possibly both improve outcomes for patients and strengthen our knowledge about the molecular biology underlying the disease.”.

Jakob Werner Hansen is currently doing his specialist training at the Department of Hematology, Rigshospitalet. He says further: “The Clinical Emerging Investigator fellowship will allow me to build my own research group with focused on the VEXAS syndrome and continue my work as combined clinician and researcher”.

Helene Charlotte Wiese Rytgaard

Helene Charlotte Wiese Rytgaard says: “One of the key challenges in medical research consists in analyzing the effects of treatments administered over time using real-world data. Here traditional statistical methods and standalone machine learning approaches may either be inapplicable or fail to yield clinically meaningful results. The obstacles that a sound statistical approach needs to deal with are continuous-time dynamics, including irregular monitoring, and complex treatment decisions, changes of patient characteristics, and health outcomes. This research project aims to develop, extend and implement advanced statistical methods integrating machine learning techniques for analyzing treatment effects in observational healthcare data, to provide more reliable tools for informed medical decision-making by patients, clinicians, and drug developers. The project will expand and enhance modern statistical causal inference tools combined with machine learning techniques and continuous-time models, to data-adaptively model the dependence between life-course events and treatment decisions, while accurately and efficiently addressing essential medical questions regarding dynamic administering of treatment. The goal is to provide a toolbox containing methods and corresponding software implementations that can be used to gain valuable insights into how the administration of treatments over time impacts patient survival and disease progression, beyond what is possible with existing methods.”

David Duchene Garzon

David Duchene Garzon says: “Identifying infected animals as early as possible allows us to minimize the spread of a pathogen and even prevent a pandemic. At the moment, we can only make sure that an
animal is infected by costly laboratory analysis. This is problematic for livestock and wildlife given the limited funds that can be spent on each animal, yet these settings are the most common source of dangerous pathogens to humans. Surprisingly, video data is not yet being used for identifying infected animals, despite great strides in video analysis in recent years.

This project will cover this gap and improve our ability to halt epidemics in their tracks. A broad range of animals will be filmed, and their behavior will be compared with their blood tests. Whether infected or not, each recording will help train computers, which will inform us about how pathogens can drive behaviour. A free app will then be developed for companies, governments, and lay people to detect infected animals at a minimal cost.”