Anna Krook

I propose studying how different tissues communicate to gain insights into overall metabolism and insulin sensitivity regulation. The research aims to explore altered inter-tissue communication’s role in metabolic disease development. Using samples from people with normal glucose levels or type 2 diabetes, we will analyze extracellular vesicles for metabolites and lipids involved in communication. We’ll consider both freely circulating factors and those carried in vesicles, such as miRNAs. Current large-scale omic analysis offers abundant data, but the challenge is moving beyond associations to understand mechanisms.

This research program seeks to fill this gap by using tissue culture and animal models to mechanistically study potential regulators of metabolism identified in our analysis. Emphasizing mechanistic validation of targets holds promise for uncovering new biology and pathways relevant to clinical intervention in type 2 diabetes.

Joanna Rorbach

Mitochondria are essential organelles in our cells that convert food into energy. This process is important for health and even subtle insufficiency in mitochondrial function can cause pathologies. Therefore, understanding mitochondrial function is highly relevant to a diverse spectrum of diseases with neurological, cardiovascular and metabolic phenotypes, as well as cancer and the aging process. Mitochondria possess their own genome that encodes proteins that are components of the energy-producing machinery called the oxidative phosphorylation system (OXPHOS). Mitochondria-encoded proteins are produced by mitochondrial ribosomes inside mitochondria. Defects in this process cause OXPHOS dysfunction, leading to diseases.
The objective of this research is to investigate mitochondrial ribosome function using advanced biophysical and molecular technologies.  In the longer term, a description of this fundamental process will allow for a better understanding of mitochondrial diseases.

Anette Wolff

Autoimmune endocrine disorders are large contributors to health threats. Today’s treatment still only manages the symptoms of disease and not the cause. Patients with monogenic endocrine autoimmunity with combined immunodeficiency syndromes where the causative gene is involved in immune activity are found with high titer cytokine antibodies (anti-IFNω and anti-IL22) in their sera, which we can use as screening tools. We here aim to screen registries of endocrine and immunodeficiency disorders for such autoantibodies and identify monogenic syndromes and novel genes responsible for such syndromes. This information can be used to inform us about more general mechanisms behind endocrine autoimmune disorders and give clues for how we can prevent or cure diseases in the future. We will furthermore investigate how tissue cells interact with immune cells in an example of such a disorder (APS-I), being possible because we have unique access to biopsies from this patient group.

Signe Sørensen Torekov

Childhood obesity is a big problem globally. This study introduces AI SYNERGY Family Care, a new way to help children stay healthy involving their families and using technology. It is different because it considers how parents’ weight and habits affect their children. The study will involve 400 families dealing with obesity, comparing this new approach with the usual care methods. The key idea is to use both medicine to help parents lose weight and an AI system that tracks family behaviors in real-time. This aims to improve how active they are, their sleep, and eating habits together. The goal is that if parents can stay healthy, their kids will too. The study hopes to change how we deal with childhood obesity, using AI to promote healthier habits that last through generations. If successful, this could transform healthcare and science, making a big impact on future generations’ health.

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.

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.