Research group Per-Johan Jakobsson
TRANSLATIONAL MEDICAL RESEARCH IN INFLAMMATORY DISEASES
We aim to explore targets and pathways in rheumatic and related diseases driven by inflammation using a pharmacological approach. We focus on the arachidonic acid cascade, development of mPGES-1 inhibitors, epigenetic modulators with associated enzymes as well as kinases. We also explore biomarkers in rheumatoid arthritis and systemic autoimmune inflammatory diseases and investigate the pathophysiological role of associated antigens and autoantibodies. We are equipped and financed for eicosanoid research, patient derived cell assays (RA, Lupus, Myositis, Systemic Sclerosis and Sjogren’s Syndrome, and recently IBD) and a platform dedicated to protein expression and antibody generation. Analytically, we perform proteomics, lipid metabolomics , cytokine profiling and pathways characterizations applying various in vitro and ex vivo systems.
Per-Johan Jakobsson received his Ph.D. from the Karolinska Institutet for work in the field of leukotrienes (1994). After finishing his doctoral studies he continued his training at Merck Frosst in Montreal, defining the MAPEG protein superfamily and subsequently characterizing microsomal prostaglandin E synthase-1. In 2013, Dr Jakobsson was appointed Professor at the Karolinska Institutet and currently combines work as a rheumatologist with translational research on disease mechanisms in inflammation with a special focus on eicosanoid pathways. He is the author of more than 130 publications.
Michael Sundström is Scientific Director for the IMI funded ULTRA-DD project, and the SGC Tissue Platforms focused on target definition and validation in oncology, neurodegenerative and inflammatory diseases. He also heads the SGC laboratory at KI, which focuses on studies of systemic auto-immune diseases and IBD using patient-derived cell and tissue based assays; as well as the generation of high quality renewable antibodies and biological probes. www.ultra-dd.org; www.thesgc.org
Helena Idborg, Assistant professor
Helena Idborg as a PhD in analytical chemistry from Stockholm University with focus on mass spectrometry, metabolomics and multivariate data analysis. Her research is focused on biomarker discovery and translational medicine within the field of inflammatory diseases. Mass spectrometry based metabolomics (e.g., targeted lipidomics and prostaglandin profiling), analysis of multiple omics data and correlation to clinical data, is applied to study and identify pathological pathways, novel biomarkers and possible drug targets in human disease.
Helena has been involved in the following projects:
Effects of mPGES-1 deletion on eicosanoid and fatty acid profiles in mice
Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus
Identification of sub-phenotypes and biomarkers in systemic autoimmune diseases (AstraZeneca Translational Science Centre / Karolinska Institutet - Joint Research Program)
Protein Profiling in Plasma Reveals Molecular Subgroups in Systemic Lupus Erythematosus
Affinity Proteomic Analysis of Serum for Prediction of Response to Methotrexate in Patients with Early Rheumatoid Arthritis: Results from the SWEFOT Trial Population
The overall aim of Marina Korotkova’s research is to gain novel understanding of regulation of lipid mediators in rheumatic diseases to improve treatment of patients. Her work focuses on molecular mechanisms affected by mPGES-1 inhibitors and COX inhibitors in different models of inflammation in vitro and in vivo and search for novel biomarkers related to anti-inflammatory or side effects of these drugs. She also investigates a role of lipid dysregulation in the pathogenesis of Rheumatoid Arthritis and Idiopathic Inflammatory Myositis to identify novel therapeutic targets.
Louise Berg coordinates the establishment of experimental platforms utilizing primary cells from patients with chronic inflammatory diseases, within the IMI-funded program ULTRA-DD. The primary aim of these platforms is to screen small molecules and blocking antibodies for effects on cellular mechanisms important in the pathogenesis of the diseases studied, which include SLE, myositis, systemic sclerosis and inflammatory bowel diseases. The following cellular assays are presently running:
B cell maturation and antibody secretion (PBMC based)
INF type I release assay (PBMC based)
IL8 and prostanoid secretion assay (whole blood)
scratch assay and IL6 secretion (skin fibroblasts)
Karin Larsson characterizes proteins involved in prostaglandin biosynthesis in tumors. She investigates the effect of selective prostaglandin E2 inhibition on tumor growth and on cells in the tumor microenvironment.
Charlotta Preger works in the IMI-funded project ULTRA-DD, WP2. Her position is part of a collaboration with the Drug Discovery and Development Platform at Science for Life Laboratory, where Charlotta works together with the Human Antibody Therapeutics group led by Dr. Helena Persson Lotsholm. Charlotta’s main tasks include generation of recombinant antibodies using phage display. She performs phage display selections, and primary screening of hits using ELISA-based methods, DNA sequence analysis, small scale purification of antibodies and affinity measurements with SPR.
Edvard Wigren works in the IMI-funded project ULTRA-DD, WP2. Edvard’s main tasks include generation of recombinant antigen for phage display and production of generated recombinant antibodies. He performs DNA construct design, cloning and small-scale expression screening and large scale parallel protein purification on an ÄKTA Xpress system.
Susanne Gräslund works in the IMI-funded project ULTRA-DD where she leads work package 2 – Protein expression and purification. Her team at KI produces selected ULTRA-DD target proteins as high-quality antigens for the phage-display selections. Generated antibodies undergo a validation process starting with ELISA screens in high-throughput format and finally the best candidates for each target are tried in immunoprecipitation followed by mass spectrometry (IP-MS) on full-length endogenous protein from a mammalian cell lysate.
Filip Bergqvist is using targeted mass spectrometry to study lipids in preclinical cancer models and clinical samples from patients with inflammatory diseases. His special interests are prostaglandins and novel anti-inflammatory compounds.
Julia Steinmetz’s Ph.D. research is focused on inflammation and its regulation by prostaglandins in rheumatic diseases and cancer. She is interested in the biosynthesis and metabolism of anti-inflammatory and pro-resolving lipid mediators such as 15-deoxy-∆12,14-prostaglandin J2 and how selective microsomal prostaglandin E synthase-1 (mPGES-1) inhibition is related to anti-inflammatory pathways. For these studies mass spectrometry is used for prostaglandin and proteomics analysis in different murine and human cellular systems.
Within the ULTRA-DD project, Yvonne Sundström works with immunologically cell based assays aimed at testing the effect of novel chemicals compounds. The read-outs focus on markers related to inflammation and autoimmunity, using primary cells from patients with SLE, myositis, IBD and others. Methods used: flow cytometry, ELISA, multiplex assays etc.
Elena Ossipova works with mass spectrometry based methods within clinical proteomics for detection of post-translational modifications of proteins, protein quantification in patient samples and analysis of pathways within the context of biological systems.
Mingmei Shang has a basic training in Biochemistry and got her PhD in Pharmacology. She is working in the patient tissue platform within the ULTRA-DD project. Her work focuses on developing patient derived cell based assays and use them to screen epigenetics probes and kinase inhibitors from the SGC consortium for inflammatory disease, e.g., real time image analysis for effects of the probes on dermal fibroblast cells from scleroderma patients. She is also interested in using gene manipulation tools to validate the lead hits and targets from our assays.