Paul Petrus

Metabolic diseases such as diabetes and obesity often occur alongside mental health conditions such as depression, though little is known about this link. Disruption of circadian rhythms increases the risk of developing such comorbidities, yet the underlying mechanisms are poorly studied. To this end, the overarching scope of this project is to dissect the circadian genes and metabolites involved in metabolic- and mental- comorbidity. This will be achieved by combining multiple circadian datasets consisting of global gene expression and metabolite measurements in various organs to identify candidate factors involved in the pathophysiology of these comorbidities. Downstream experiments in cell cultures and mouse models will be utilized to dissect the mechanisms. Ultimately, the goal is to design novel therapies that targets circadian rhythms to treat metabolic- and mental- comorbidities.

Andreas Mæchel Fritzen

Certain types of fats that exist in milk and coconut- and palm kernel oil have health benefits. These fats – referred to as medium-chain fatty acids – help control blood glucose levels and also increase the feeling of satiety and at the same time enhance the body’s metabolic rate (i.e., burn more calories), which can promote a healthy body weight and lower the risk of developing metabolic diseases. How these effects happen in the body is currently unknown – but important to elucidate. After considering how these medium-chain fatty acids are digested and how and where they are metabolized in the body, I will investigate the new hypothesis that they act on the liver to release special factors that mediate the health benefits in the rest of the body. I want to first identify those factors and then verify that they actually drive these health beneficial effects in the body.

Panu Luukkonen

Non-alcoholic fatty liver disease (NAFLD) affects up to 1 in 4 people globally and predisposes to type 2 diabetes, heart disease and liver disease. The mechanisms underlying NAFLD remain unclear. Here, we study whether dysfunction of the cellular ‘energy motors’ – mitochondria – is a key mechanism underlying NAFLD in humans. To this end, we use state-of-the-art stable isotope methods to study hepatic mitochondrial function in individuals with and without NAFLD in response to modifiable risk factors and to currently available treatments. We also use large population-based cohorts to study whether genetic variants predispose individuals to hepatic mitochondrial dysfunction, and whether those individuals are also predisposed to NAFLD. Finally, we investigate in mice whether a pharmacological increase in mitochondrial function can ameliorate NAFLD. This project is expected to provide important new knowledge on the pathogenesis of NAFLD, which may help to develop new pharmacotherapies and to identify individuals who are at a particularly high risk of NAFLD.

Karolina Sulek

Imagine a life with disease, where you need to control your lifestyle at every step. Medication, namely insulin injections, glucose levels testing, and proper diet is a must for the everyday disease management. This is diabetes. Now add to this equation chronic pain in your legs and arms, possibility of amputation or even death. This is diabetic neuropathy. For unknown reasons to scientists, significant proportion of people struggling with blood glucose management develop this condition, where damaged nerves lead to chronic pain in their limbs. Steno Diabetes Centers provide support to people affected by diabetes. My project merges knowledge and skills from clinical and technological advancements in the pioneering sector to provide better diagnostics for patients affected by diabetic neuropathy. With this project I aim to personalize diabetic care using top-drawer modern technology within analytical chemistry and IT in search for novel biomarkers of neuropathy.

Elisabet Stener-Victorin

Polycystic ovary syndrome (PCOS) is the leading cause of female infertility and linked to type-2 diabetes and cancer. Progress in managing the disorder is hindered by lack of insight into the underlying mechanisms. We know that male hormones plays a key role and that PCOS runs in families. Recently we made the discovery that PCOS-like symptoms, induced by exposing pregnant mice to male hormone, are passed down from mothers to great-granddaughters. Moreover, we have indications that sons can transmit the disease as well.

I will take a multidisciplinary approach to get better insights into how PCOS is passed on in families. We will use human and mouse studies as well as state-of-the-art molecular techniques to dissect the key mechanisms that influence how the syndrome is passed on across generations both by women and men. My vision is to open new horizons for prevention strategies rather than managing symptoms, thereby markedly reducing the burden of the disease in both women and men.

Anu Suomalainen Wartiovaara

Diabetic retinopathy is the most common cause of blindness in working age people. The disease shows overgrowth of vasculature in the retina, which causes rupture of microvessels and edema in the tissue, with risk to retinal detachment and decreasing eyesight.  Still, the underlying molecular mechanisms are poorly known, hampering development of treatments. We have found that a specific type of (DEL) cell in retina, previously considered to be “supportive”, has an important role in maintaining physiological balance in retina. If the mitochondria, the cellular “power plants”, are dysfunctional in these cells, the retinal vasculature shows overgrowth and develops disease signs mimicking diabetic retinopathy. This exciting project has high potential to find mechanistic targets amenable for interventions. We will explore the pathophysiology in deep molecular detail, using state-of-the-art tools and our long expertise in metabolism, to discover the molecular basis of neovascular retinopathy of diabetes type.

Christoffer Clemmensen

The increasing prevalence of obesity represents a growing threat to public health. Challengingly, obesity is a rather treatment-resistant condition and many patients do not obtain the benefits of pharmacological or lifestyle-based interventions. Notably, human genetic studies point to an important role for glutamatergic neurotransmission and neurostructural changes in body weight regulation and obesity pathogenesis. However, this biology is incompletely understood and has yet to undergo pharmacological scrutiny for obesity treatment. In this project proposal the overarching aim is to dissect the importance of the glutamatergic NDMA receptor and its related signaling complex, in physiological and pharmacological regulation of body weight homeostasis. This research holds promise to illuminate a hitherto unknown signaling pathway essential for the regulation of energy homeostasis and to evaluate its druggability for obesity treatment.

Tuomas Kilpeläinen

Obesity often leads to insulin resistance and an increased risk of type 2 diabetes. However, not all individuals with obesity are similarly affected. Given the same weight gain, individuals may be either protected from or predisposed to metabolic dysfunction. This variability has been attributed to individual differences in the characteristics of the excess adipose tissue. However, there remains a lack of understanding of the specific adipose tissue properties that underlie differential responses to weight gain and obesity. The aim of the present project is to understand the adipose tissue mechanisms that either protect from or predispose to insulin resistance and type 2 diabetes. The project builds on human genetic findings made in large populations and applies a range of approaches to connect the genetic variants to adipose tissue biology. The new understanding emerging from the project may point towards more effective ways to treat insulin resistance and type 2 diabetes.

Thomas Jensen

Among its many important effects, the hormone insulin binds to antennas on heart and skeletal muscle cells and transmits a signal inside to open doorways called GLUT4 in the cells to allow glucose to enter. The ability of insulin to stimulate glucose entrance fails in a process called insulin-resistance. Insulin resistance contributes to the early development of type 2 diabetes and cardiovascular disease and prevention and treatment strategies are therefore desirable. Insulin resistance is commonly explained by the insulin antenna failing to transmit its signal, but we suspect – based on preliminary work – that the inside of cells becomes progressively messier in insulin resistance and that GLUT4 is instead moved out of reach of the insulin signal. To test this idea in-depth in humans, we will develop new advanced microscopy tools to analyse human skeletal muscle biopsies and human 3D stem cell models of heart and skeletal muscle.

Ana Teixeira

This research program will investigate how the spatial organisation of the insulin receptor regulates its function and aims to contribute to the development of new strategies for the treatment of diabetes. Diabetes has very high and increasing prevalence worldwide. Insulin replacement therapy helps patients to keep their glucose levels within an acceptable range but it is still challenging to mimic the dynamics of endogenous insulin release, while avoiding dangerous hypoglycaemia. Therefore, there is a need to find new ways to implement insulin replacement therapy. The approach presented in this proposal uses beyond state-of-the-art nanotechnology methods to explore a new angle in diabetes treatment. Instead of focusing only on blood insulin concentrations as the treatment variable, we propose that the nanoscale organization of insulin drugs can be used as a design parameter to improve insulin replacement therapy.