Our research section focuses on molecular epidemiology with emphasis on cardiometabolic disturbances like obesity, insulin resistance and their role in the development of cardiovascular diseases.
We aim to identify novel biomarkers using several -omics approaches, address the issue of causality using a Mendelian Randomisation approach, and translate findings from large-scale genome-wide association studies into clinically relevant findings using high-throughput cell-based and zebrafish model systems. We also apply traditional epidemiological methods in national registers and large biobanks.
Our ambition is to be an international, vibrant and creative research environment with many exciting projects within large-scale genetic and biomarker projects. Our research is projected to lead to new important insights of disease mechanisms, which in turn can facilitate development of new treatments of these diseases, as well as to new biomarkers of disease for improved risk prediction and prognostics.
Projects - Molecular epidemiology
Our research group has been taking a very active part in the various ongoing large-scale international genetics projects within the area of cardiovascular and metabolic disorders in the past five years. The work within these consortia has led to landmark papers dissecting the genetic architecture of complex traits. Prof. Ingelsson has been the corresponding author of several of these large consortia papers, which were published in leading journals, while in others we have had an important role in the writing group. As a whole, these papers have not only identified hundreds of novel genetic loci associated with cardiovascular traits, but also dramatically increased the understanding of the genetic architecture of complex traits and the biology underlying these conditions.
Since 2010, we have also been working with Mendelian randomization (MR) as a method to address causality - a key concept in clinical medicine and epidemiology. Several of these international projects that Ass. Prof Fall and Prof. Ingelsson have now been published in high-impact journals, and we have several additional projects using this methodology in the pipeline. We have also taken part in more methodological work in this field.
For in vitro studies, we use human SGBS adipocytes and HepG2 hepatocytes. For knockdown and overexpression experiments, we transfect cells using CRISPR-Cas9 constructs and lentivirus. We assess the effect of knockout or overexpression of candidate genes on basal and insulin-stimulated glucose uptake (using 14C-labeled deoxyglucose) and lipolysis (measuring glycerol after insulin and/or isoprenalin exposure), as well as insulin signaling proteins and adipogenesis. We address downstream effects of gene knockdown or overexpression using transcriptomic and metabolomic profiling on cell lysates.
We have had a strong interest in studies of biomarkers measured in human biosamples in the past decade, and have been working extensively with prediction of cardiovascular disease by use of both traditional and more novel biomarkers and by use of different statistical metrics for prediction.
We have a range of ongoing projects using transcriptomics, epigenomics, proteomics, metabolomics, microbiomics - all aiming at increase the biological knowledge of cardiovascular diseases and to identify new biomarkers and drug targets. In proteomics, we are working with the proximity extension assay and have published several papers during 2015, one of them selected as one of the scientific highlights for SciLifeLab in 2015. In metabolomics, we are using liquid chromatography (LC)- and gas chromatography (GC-) tandem mass spectrometry (MS/MS) methods, and we have run analyses in about 5,500 samples from several longitudinal cohort studies and published several important papers on coronary heart disease and insulin resistance. Regarding microbiomics, we are currently setting up methods and analysing 400 pilot samples in our own lab to assess key microbiome characteristics and in the future link these to important phenotypes. Over the next few years, we plan to continue to analyse new samples using these methods, combine data across studies and data types, and to use -omics to improve knowledge about cardiometabolic diseases.
We are active in using traditional epidemiology including two papers reaching high public attention in 2015. One of these led by Prof. Ingelsson investigated novel predictors of mortality (Altmetric 535, top 5% of all research scored) and the other one led by Dr Fall investigated the association of animal exposure on childhood asthma risk (Altmetric 430, top 5% of all research scored). We continue to work on these two unique resources, the UK Biobank (502,000 participants) and the Swedish national registers with other important public health questions.
Significance and novelty
Our research program combines comprehensive characterization in humans using both -omics methods and detailed phenotyping, with experiments in both in vitro and in vivo model systems in an integrative fashion providing a translation-back translation framework. We have access to unique study materials, state-of-the art methods, and a strong track record of successful projects in this field. Our work is anticipated to lead to new important insights into the pathophysiology of obesity, lipid metabolism, type 2 diabetes and cardiovascular diseases, and to new approaches to prevention and treatment that could have a huge impact on public health.