Recruited fellows to Novo Nordisk Fellowship Programme at Karolinska Institutet
I studied biology and physiology at the University of Nantes, and joined the Institut du Thorax (Nantes, France) for my PhD. My PhD project was focused on the role of adipose tissue in the regulation of metabolic homeostasis in a particular condition of adipose tissue failure: generalized lipodystrophy. Using mouse and cell model, I studied the consequence of seipin deficiency on adipocyte differentiation and function; and used pharmacological approaches targeting adipose tissue to improve the metabolic complications associated with lipodystrophy.
In September 2016, I started my Novo Nordisk Fellowship at the Karolinska Institutet and joined the Integrative Physiology group, headed by Pr Juleen Zierath and Pr Anna Krook. Regular physical activity has beneficial effect in type 2 diabetes, leading to an improvement of whole-body energy homeostasis. My project is to investigate the crosstalk between skeletal muscle and adipose tissue, using both cell models mimicking exercise and biopsies from patients before/after exercise. Our aim is to identify new factors secreted by skeletal muscle that act on adipocyte and mediate the beneficial metabolic effect of exercise on adipose tissue.
Project title: Immuno-metabolic modulation of skeletal muscle insulin sensitivity.
I graduated in Biochemistry at the Complutense University of Madrid. During my PhD at the Institute of Food Science, Technology and Nutrition (ICTAN-CSIC) I studied the molecular mechanisms involved in the antidiabetic effect of dietary polyphenols. I have studied how these compounds modulate different signalling pathways, improving insulin sensitivity and glucose tolerance as well as they prevent oxidative stress under diabetic situation. Additionally, I conducted a research stay at Gothenburg University and at Texas Children’s Hospital where I deepened my knowledge on the molecular bases of diabetes and obesity and on the relation between diet and health respectively.
I started my Novo Nordisk Fellowship in October 2016 and joined the Renal and Cardiovascular Research group, headed by Prof Mattias Carlström. Oxidative stress and Nitric Oxide deficiency can contribute to the development of Type 2 Diabetes (T2D), or its adverse complications. Adenosine can influence vascular and metabolic functions and modulates oxidative stress. Our translational project aims at characterizing the mechanisms whereby adenosine and nitric oxide signalling modulates oxidative stress, and how this influences metabolic, microvascular and immune cell functions in T2D
Project title: Modulation of adenosine receptor signalling provides novel therapeutic strategies in Type 2 diabetes.
I studied Pharmacology at the University of Bristol, carrying out my master’s project within the Heart Failure department at GlaxoSmithKline in Philadelphia. I obtained my DPhil at the University of Oxford, focusing on novel molecular therapies for the treatment of Familial Hypercholesterolaemia. Here, I worked on the pre-clinical development of a non-viral gene therapy approach and a small molecule approach to deliver and upregulate functional copies of the low-density lipoprotein receptor respectively. Through this work, I became interested in lipid dysregulation and its role in the development of cardiometabolic disease.
I started my Novo Nordisk Fellowship in November 2016 joining the Lipid Laboratory under the supervision of Associate Professor Ingrid Dahlman. During the 3-year fellowship I will be investigating the role of long non-coding RNA in white adipose tissue function and its contribution to the development of insulin resistance and type-2 diabetes. The long non-coding RNA transcriptome and its relation to defining white adipose tissue dysfunction is completely unexplored. In the Lipid Laboratory we will apply -omics technologies and high throughput gene manipulation, together with sensitive metabolic assays, to define new long non-coding mediators of adipose dysfunction in obesity and insulin resistance. In this translational approach findings in cell models will be validated in large clinical cohorts.
Project title: Impact of fat cells expressed long non-coding RNAs on human insulin resistance.
I got my Bachelor’s degree in Health biosciences and Master’s degree in Drug development at University of Turku, Finland. During my PhD at Turku PET Centre, I focused on positron emission tomography (PET) imaging of inflammation in atherosclerosis. The evaluated PET radiotracers were targeted to macrophages in atherosclerotic lesions. I also studied the use of PET imaging for the assessment of therapy responses.
Currently I am starting the Novo Nordisk Fellowship in a project led by Assoc. Prof. Stephen Malin and Prof. Göran Hansson in Department of Medicine. Elevated blood cholesterol levels are associated with cardiovascular disease and type 2 diabetes. The project will focus on evaluating the effects of rising cholesterol levels to glucose homeostasis, immune response in different tissues, as well as gene expression in vascular wall. In addition, the respective effects of hypercholesterolemia reversal will be evaluated. The studies will be conducted in mouse models that permit induced changes in blood cholesterol levels. Finally, the aim is to translate the concept to human disease by evaluating samples from patients with familial hypercholesterolemia.
Project title: The molecular and cellular consequences of acute hypercholesterolemia.
Dr Kelvin Kwok
I studied biochemistry at the University of Oxford. During my PhD studies at the University of Hong Kong, I investigated the role of visceral adipose tissue inflammation in the accelerated development of atherosclerosis in obese mice. Specifically, I examined how obesity-induced JNK activation in visceral fat promotes atherosclerotic plaque development in the aorta through the actions of adipokines.
In October 2017, I started my Novo Nordisk Fellowship under the co-supervision of Dr Carsten Daub from the Department of Biosciences and Nutrition, and Prof Mikael Rydén and Prof Peter Arner from the Department of Medicine. It has recently been demonstrated in humans that obese white adipose tissue exhibits a markedly altered insulin-induced gene expression regulation in vivo. My current project aims to comprehensively identify the responsible regulatory elements and to decipher the mechanisms that underlie this impairment in transcriptional regulation in response to insulin, in an unbiased manner using Cap Analysis Gene Expression (CAGE).
Project title: Elucidating the molecular mechanisms behind impaired insulin-induced transcriptional regulation in human adipose tissue.
Dr Noah Moruzzi
After my graduation in Human Feeding and Nutrition Sciences at the University of Perugia, I joined Karolinska Institutet as Ph.D. student in the Growth and Metabolism Group (Dept. of Molecular Medicine and Surgery, MMK), focusing on cell and mitochondrial metabolism during hyperglycemia in human primary cells. In the last part of my doctoral studies I relocated to the Helmholtz Zentrum München working on the primary cilium and its link with cellular metabolism before to finalize my thesis “Interplay between mitochondria, primary cilium, diabetes and its complications”. During the last year, I worked as a Quality Control and Data Management Consultant in the biotech image analysis company Definiens AG (Münich).
In October 2017, I came back to Karolinska as Novo Nordisk Postdoctoral Fellow in the section of Signal Transduction (MMK) as part of Ingo Leibiger´s group. The project I´m involved in is focusing on understanding the development and progression of beta cell insulin resistance and failure in diabetic mouse models to identify novel target and strategies for treatment of T2DM. Moreover, we will study the insulin receptor A and B isoforms using aptamers as tools to selectively activate/inactivate these receptors and thus study their biological significance in cells and tissues.
Project title: The role of insulin receptor isoforms in selective insulin signaling in pancreatic beta cell physiology/pathology.
I completed my PhD in the group of vascular physiology at the department of Experimental Medicinal Science at Lund University Sweden in February 2017. My main research focus has been on the host defence peptide LL-37 and its effects on human cell viability. During my PhD and subsequent employment, I have also investigated cytotoxic and immunomodulatory properties by a number of other proteins and small molecules. My earlier academic background lies primarily in chemistry, where I worked with semi-synthesis and isolation/structure elucidation of natural products.
I will begin my Novo Nordisk fellowship in January 2018 during which I will be working with Hjalmar Brismar and Anita Aperia at the Pediatric Cell and Molecular Biology lab of the Department of Women’s and Children’s Health. Diabetic nephropathy is a common complication for diabetic patients which often results in chronic kidney disease. I will investigate an early event in the nephropathy pathogenesis in which glucose and/or albumin triggers apoptosis of mesangial and proximal tubular cells. Additionally, a Na,K-ATPase-signaling cascade which attenuates the cell death will be investigated, in order to gain mechanistic understanding of the apoptosis and its medical significance.
Project title: A novel concept for origin and treatment of diabetic nephropathy.
After my graduation from the Saint-Petersburg State University, I studied as a PhD student at the Institute of Experimental Medicine in Saint-Petersburg, Russia. My main research focus has been on the genes involved in atherosclerosis development. I have studied the influence of pro- and anti-atherosclerotic stimuli on the expression of various genes (such as C3, apoA-I and ABCA1) as well as protein production in human hepatoma cells and human macrophages. During the project I have discovered signaling cascades and characterized new protein complexes between important metabolic transcription factors, involved in these processes.
I will begin my Novo Nordisk fellowship in September 2018 in a project led by Dr. Peder Olofsson in Department of Medicine. The project will focus on the role of TChAT cells in human vascular inflammation and atherosclerosis, as well as their function in integrating immune and nervous systems. To this end, TChAT cells will be identified in lesions and markers for their isolations will be found. This will allow us to isolate human TChAT and functionally characterize them. The next step of the project will involve unveiling mechanisms of TChAT differentiation and activation. Regulation of ChAT expression will be studied. The low resolution undirected network representation of the differentially expressed ChAT T-cell genes and their most frequent interactors will be identified and used to test for potential disease relevance.
Project title: Neural regulation of inflammation in atherosclerosis.
Dr Lars Paeger
I studied biology at the University of Cologne and started to work as an electrophysiologist during my diploma thesis where I analyzed ion channels of interneurons in the antennal lobe of the cockroach Periplaneta Americana. During my PhD studies, I took the opportunity to work in the field of the neuronal control of energy homeostasis. Specifically, I am interested in the intrinsic mechanisms, which define the excitability of neurons in the hypothalamus controlling food intake and energy expenditure and how these are altered by neuromodulation or by chronic alterations, i.e. when animals are exposed to a high-fat-diet and subsequently develop diet-induced obesity. I found that the activity of satiety signaling POMC neurons is decreased in obese animals, in part as a consequence of changes in Ca2+ handling in these cells. Further, I could identify the catecholamine noradrenalin as new modulator of cells in the hypothalamus controlling energy homeostasis. After my PhD I stayed as a postdoc in Cologne and continued and expanded my research in this particular system.
In the beginning of 2019 I started in the lab of Christian Broberger after being awarded with a Novo Nordisk postdoctoral fellowship. Particularly, we aim to characterize somatostatin expressing neurons in the periventricular nucleus of the hypothalamus, a population that has not been described in detail yet. Since these cells are major components of the growth hormone axis we want unravel the contribution to glucose metabolism specifically and energy homeostasis in general. To this end, we will use electrophysiological tools in-vitro and in-vivo combined with behavioral analysis and assessment of metabolic parameters in mice. The knowledge obtained within this project helps to further understand the central regulation of metabolism and may open new targets and strategies in the pharmacological treatment of metabolic disorders and obesity.
Project title: The central control of growth hormone release – electrophysiology and functional role of neuroendocrine somatostatin neurons.
Dr Thomas Ebert
I am a Clinician Scientist working on adipocytokine crosstalk linking obesity and diabetes mellitus with cardiometabolic complications. I graduated from Medical School at the University of Leipzig, Germany and obtained my M.D. in 2010. In my research, I have focused on the effects of adipose tissue-secreted proteins especially on diabetic kidney disease using human studies, as well as animal experiments. In 2018, I finished my Habilitation thesis on adipocytokines as predictors of cardiometabolic diseases.
In 2019, I started my Novo Nordisk Fellowship at Karolinska Institutet in the Division of Renal Medicine at the Department of Clinical Sciences, Intervention and Technology (CLINTEC). I work in the group of Peter Stenvinkel and Annika Wernerson investigating novel genes and proteins that are involved in development and progression of chronic kidney disease and its vascular complications. In more detail, we focus on the identification of pathways contributing to early vascular ageing frequently observed in patients with chronic kidney disease. The overall aim of my work is to establish potential therapeutic targets aiming on treatment of chronic kidney disease but also its cardiometabolic and vascular comorbidities and complications.
Project title: Chronic kidney disease – exploration of novel diagnostic, preventive and therapeutic targets for an emerging public health priority.
Dr Pauline Vercruysse
Postdoctoral Fellow 2016-2017
Project title: Can diet-induced metabolic disease trigger neurodegeneration when combined with impaired SNARE protein function?
PI: Christina Bark
Dr Ester Bachar-Wikström
Postdoctoral Fellow 2016-2018
Project title: Accelerating regeneration of β-cells and restoration of normoglycemia by reinforcing the gut-pancreas axis in zebrafish.
PI: Olov Andersson
Dr Soile Tuomela
Postdoctoral Fellow 2016-2018
Project title: Gene-environment interaction studies for the identification of novel disease mechanisms and therapeutic targets in Type 1 diabetes – focus on single nucleotide polymorphisms (SNPs) in beta cell express genes.
PI: Malin Flodström-Tullberg
Dr Lars Ketscher
Postdoctoral Fellow 2016-2018
Project title: Exploring myo-exosomes in health and disease.
PI: Jorge Ruas
Dr Montserrat Visa
Postdoctroal Fellow 2016-2019
Project title: In vivo imaging of pancreatic β-cell Ca2+ signaling in health and disease.
PI: Per-Olof Berggren
Dr Nicole Schmitner
Postdoctoral Fellow 2016-2019
Project title: Drug discovery in zebrafish for promotion of transdifferentiation to β-cells – and thereby potentiation of β-cell regeneration.
PI: Olov Andersson