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 investigate biomarkers in rheumatoid arthritis and systemic autoimmune inflammatory diseases and investigate e.g. 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 e.g. perform proteomics, lipid metabolomics and cytokine profiling; often focused on the effects of prototype drugs (chemical and antibody based biological probes) targeting under-explored areas of human diseases driven by inflammation.
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
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.
Kristina Edfeldt works as project manager supporting our efforts in the IMI-JU funded immunology program and the Karolinska patient-derived cell assay team within the SGC Tissue Platforms. She manages the financial aspects of the ULTRA-DD project and is responsible for reporting and managing contacts with the project’s other pharma and academic partners. She manages external research grants and grant applications from private and governmental funding agencies, national as well as international.
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.
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
Andrea Introini works as project leader within the SGC Tissue Platform to streamline the use of clinical specimens for early drug discovery in inflammatory bowel disease (IBD), a relapsing-remitting chronic inflammatory disorder of the gastrointestinal tract. With a background in human mucosal immunology and experimental medicine, his main task is to devise blood and tissue-based cell assays for phenotypic drug screening. Experimental results are integrated with patient molecular profiling by multi-omics to guide target and biomarker identification in a personalized fashion.
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.
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.
Carolyn Marks works in the IMI-funded ULTRA-DD project, WP2. Her position is part of a collaboration with the Drug Discovery and Development Platform at Science for Life Laboratory, where Carolyn works together with the Human Antibody Therapeutics group, led by Dr. Helena Persson Lotsholm. Within ULTRA-DD, Carolyn produces and validates antibodies primarily for the ALS Reproducible Antibody Platform (ALS-RAP) project. ALS-RAP is a collaboration between KI, University of Oxford, and McGill University with the aim to generate, identify and characterize the highest quality, renewable, recombinant antibodies for prioritized ALS-relevant antigens and to make them freely available to the ALS community. Carolyn´s main tasks include generation of recombinant antibodies using phage display technology, high-throughput binding and specificity screening, DNA sequence analysis, small scale purification of antibodies, SPR affinity measurements, and KO validation via CRISPR/Cas9 genome-editing.
Charlotta Preger is a PhD student in the IMI-funded project ULTRA-DD, WP2. She is working with recombinant antibody generation using phage display, and is studying aminoacyl tRNA syntheses and their connection to rheumatic autoimmune diseases.
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.
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.
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.