Michael Sundström Group
Early drug discovery research in chronic inflammatory diseases
The SGC Karolinska laboratory focus on exploring novel target biology for future drug development. This is done with focus on chronic inflammatory diseases, neurodegenerative diseases and liver fibrosis. We are part of the Structural Genomics Consortium (SGC), a public-private partnership that supports the discovery of new medicines through an open science model. Our research focuses on three scientific areas i) patient derived cell-based assays and models ii) generating recombinant proteins and antibodies to selected targets from our collaborative network, and iii) identification, sourcing and validation of chemogenomic tool compounds for selected target families and proteins, such as GPCRs and Ion Channels. We have a particular interest in studying inflammation and autoimmune disease mechanisms in inflammatory bowel diseases, neuroinflammation and liver fibrosis. We have research efforts in protein and antibody production, cell culture, patient-derived cell-based assays and models based at CMM. Through collaboration with Evert Homan and co-workers (Department of Oncology and Pathology, KI) within the EUbOPEN project (IMI), we also perform studies in the areas of chemogenomics and cheminformatics. All research is performed as open science studies; immediately making all research data and outputs publicly available.
SGC Karolinska is a partner in the EUbOPEN project (Enabling and Unlocking biology in the OPEN), a consortium that has been granted almost EUR 66 million (SEK 690 million) by the European Innovative Medicines Initiative (IMI) and its partners. The funds are used to develop, test, and make available chemical substances and other research tools that can pave the way for the development of new medicines and treatments for diseases such as inflammation and cancer. The project involves 22 partners from academia and industry who together work to develop and validate high-quality drug-like chemical substances and other research tools such as antibodies, and subsequently profile these research tools in translational medical studies. Michael Sundström, Scientific Director, SGC Karolinska, leads the operation together with other researchers at Karolinska Institutet.
The consortium will also test and analyse the substances in disease-relevant models of human tissue in the fields of immunology, oncology and neuroscience. Results, chemical substances, antibodies, analysis protocols and associated research data are made openly available to the research community without restrictions: https://www.eubopen.org/
Michael Sundström received his PhD from Uppsala, followed by Postdoctoral studies at Karolinska Institute. From 1993-2000 he was at Pharmacia as Director for structure-based drug design and oncology R&D portfolio management. Between 2001 and 2003 he held senior positions at the Swedish Biotechs Actar and Biovitrum. In 2003 he joined the Structural Genomics Consortium (SGC) at the University of Oxford, as Chief Scientist. In 2007 he assumed the position as Managing Director for the Novo Nordisk Foundation Center for Protein Research (Copenhagen). In 2011, he was Vice President of Discovery Research at Karolinska Development. He then re-joined the SGC in mid-2014, as Scientific Director of SGC Karolinska. Michael has three main responsibilities within the SGC; i) member of the global research leadership team coordinating projects and activities of common interest within the consortium; ii) site head for SGC Karolinska and iii) main scientific focus and responsibility for the SGC Tissue Platforms in Stockholm, Frankfurt, Toronto and Montreal; working to establish high quality cell-based assays using patient-derived cell systems in inflammation, oncology and neurodegenerative diseases. Since April 2022, Michael is also the Director of the Center for Molecular Medicine (CMM), at Karolinska Institutet and the Karolinska University Hospital.
Oliver Arnolds, PhD, Postdoc, firstname.lastname@example.org
Oliver completed is PhD in Biochemistry at the Ruhr University of Bochum, Germany, in 2020 with focus on biomolecular NMR spectroscopy and protein biochemistry. He joined the SGC in Stockholm at the Karolinska Institutet as a postdoctoral researcher for the Women’s and Children’s Health Initiative to identify potential protein targets for non-hormonal contraceptives. Oliver champions the characterization of the a/b Hydrolase Domain 2 (ABHD2) as well as other ABHDs and assay development for these proteins.
Kristina Edfeldt, PhD, Project manager, email@example.com
Kristina is an experienced project manager and research coordinator with expertise in managing and supporting large global research projects in life science. She has a PhD in immunology from Karolinska Institutet and postdoctoral experience within the field of innate immunity from UCLA.
Opher Gileadi, PhD, Team Leader, firstname.lastname@example.org
Opher Gileadi obtained his PhD in Biochemistry at the Hebrew University and was then a postdoctoral fellow at Stanford University Medical School. Subsequently he led a research group at the Weizmann Institute of Science. From 2004-2021 he was both at SGC University of Oxford, first as head of the Biotechnology group, then as Principal Investigator of the Genome Integrity & Repair Group as well as Head of the SGC Kinase Chemical Biology Center at the State University of Campinas (UNICAMP). In 2021 Opher took a position as Executive Director, Protein Science and Structure at Exscientia, but re-join the SGC at Karolinska in 2023 as Head of the Protein Science team, focussing on developing antibodies and target-enabling packages (TEPs) for under-investigated proteins of humans and pathogens.
Kang-cheng Liu, PhD, Postdoc, email@example.com
Kang-cheng Liu is a postdoc at SGC-Karolinska working with Opher Gileadi in the Protein Science team on high throughput protein production and recombinant antibody generation for the IMI-funded EUbOPEN project. Kang-cheng is a biochemist with expertise in mammalian protein expression and enzymology and joins the team from Umeå University where he did a postdoc with Prof. Richard Lundmark investigating caveolae coat-protein Cavins.
Ali Okhovat, MSc, PhD student, firstname.lastname@example.org
Ali is a PhD student in the Tissue Assay team at SGC-Karolinska working on inflammatory bowel disease (IBD). The aim of his thesis project is to functionally characterize mechanisms that promote intestinal regeneration and determine their translational relevance by (i) evaluating the translational potential of already identified pro-regenerative pathways (e.g. oxysterol-LXR), and (ii) establishing an automated high throughput drug screening platform for testing intestinal regeneration using patient-derived intestinal organoids, alone or in co-culture setting with patient-matched fibroblasts from inflamed and non-inflamed biopsies. The ultimate goal is to find alternative treatment modalities for IBD. Ali’s scientific background is in human immunology, and he has a MSc degree from Örebro University, Sweden.
Mingmei Shang, PhD, Researcher, email@example.com
Mingmei is an experienced cell biologist with a PhD in Pharmacology. She has broad research experiences in drug discovery and early clinical development for both small molecule entities and biologics. Currently she focuses on developing and miniaturizing patient-derived cell-based assays for systematic autoimmune diseases, such as Multiple Sclerosis, Systemic lupus erythematosus et al., then using these assays to identify novel drug targets through screening chemical probes and chemogenomic library targeting the ‘undruggable’ human genome and validating the top hits with gene manipulation tools and omics technologies.
Consortia & networks
The Structural Genomics Consortium (SGC), led from Toronto, Canada, is a pre-competitive public-private partnership in the areas of structural and chemical biology, and drug discovery that supports the discovery of new medicines through open science. The SGC was founded in 2003 with two main laboratories at the Universities of Toronto and Oxford. The current SGC laboratories are located at Goethe University Frankfurt, Karolinska Institutet, McGill University, University College London, the University of North Carolina Chapel Hill and the University of Toronto and constitute a network of approximately 250 scientists. SGC scientists collaborate with scientists in each of its partner companies, currently Bayer AG, Boehringer Ingelheim, Bristol Myers Squibb, Genentech, Janssen, Merck, Pfizer and Takeda.
The SGC Karolinska has, through the EUbOPEN project, established collaborations with leading scientists at Karolinska Institutet, SciLifeLab and internationally:
Maja Jagodic https://ki.se/en/cns/maja-jagodics-research-group
Pekka Katajisto https://www.katajisto-lab.com/
Volker Lauschke https://ki.se/en/fyfa/lauschke-lab-personalized-medicine-and-drug-development
Anna-Lena Gustavsson https://www.scilifelab.se/facilities/cbcs
Evert Homan http://helleday.org/
Mats Ohlin, Lund University https://www.immun.lth.se/research-new/senior-researchers/mats-ohlin/
David Gloriam, University of Copenhagen https://drug.ku.dk/disciplines/peptides-and-proteins/gloriam-group/
Rob Leurs & Barbara Zarzycka, Free University Amsterdam https://research.vu.nl/en/persons/rob-leurs
Daniel Martinez Molinas, Pelago Bioscience https://www.pelagobio.com/
The EUbOPEN project’s funding comes partly from IMI, and partly from the pharmaceutical industry organisation the European Federation of Pharmaceutical Industries and Associations (EFPIA), IMI-associated partners and other international partners. IMI is a collaboration between the EU and the European pharmaceutical industry, the purpose of which is to accelerate the development of and access to new innovative medicines in areas of high unmet medical needs.
SGC Karolinska receives funding from the Bill and Melinda Gates Foundation for involvement in a project on women’s health and non-hormonal contraception.
The SGC is a registered charity (no: 1097737) that receives funds from; AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genentech, Genome Canada through Ontario Genomics Institute [OGI-196], EU/EFPIA/OICR/McGill/KTH, Diamond Innovative Medicines Initiative 2 Joint Undertaking [EUbOPEN grant 875510], Janssen, Merck KGaA (aka EMD in Canada and US), Merck & Co (aka MSD outside Canada and US), Pfizer, São Paulo Research Foundation-FAPESP, Takeda and Wellcome [106169/ZZ14/Z].
PhD theses from the lab
Filip Bergqvist: Inhibition of mPGES-1 as therapeutic strategy in inflammation and cancer, 2019.
Charlotta Preger: Aminoacyl tRNA synthetases and their connection to autoimmune rheumatic disease, 2022.
The SGC encourages collaborations with laboratories across the globe, focused on proteins of medical relevance and their modulators of functions, such as small molecule inhibitors and antibodies. Contact: Opher Gileadi (firstname.lastname@example.org).
Cellular shape reinforces niche to stem cell signaling in the small intestine. Pentinmikko N, Lozano R, Scharaw S, et al. Sci Adv. 2022;8(41)
Identifying novel B-cell targets for chronic inflammatory autoimmune disease by screening of chemical probes in a patient-derived cell assay. Sundström Y, Shang MM, Panda SK, et al. Transl Res. 2021;229:69-82.
Generation and validation of recombinant antibodies to study human aminoacyl-tRNA synthetases. Preger C, Wigren E, Ossipova E, Marks C, Lengqvist J, Hofström C, et al J Biol Chem 2020 Oct;295(41):13981-13993
Anti-Inflammatory Properties of Chemical Probes in Human Whole Blood: Focus on Prostaglandin E2 Production. Bergqvist F, Sundström Y, Shang MM, Gunnarsson I, Lundberg IE, Sundström M, et al Front Pharmacol 2020 ;11():613
A genetics-led approach defines the drug target landscape of 30 immune-related traits. Fang H, De Wolf H, Knezevic B, Burnham KL, Osgood J, et al Nat Genet 2019 07;51(7):1082-1091
Circulating Levels of Interferon Regulatory Factor-5 Associates With Subgroups of Systemic Lupus Erythematosus Patients. Idborg H, Zandian A, Ossipova E, et al. Front Immunol. 2019;10:1029.
Patients with anti-Jo1 antibodies display a characteristic IgG Fc-glycan profile which is further enhanced in anti-Jo1 autoantibodies. Fernandes-Cerqueira C, Renard N, Notarnicola A, Wigren E, Gräslund S, Zubarev RA, et al Sci Rep 2018 12;8(1):17958
A DNA-Encoded Library of Chemical Compounds Based on Common Scaffolding Structures Reveals the Impact of Ligand Geometry on Protein Recognition. Favalli N, Biendl S, Hartmann M, Piazzi J, Sladojevich F, Gräslund S, et al ChemMedChem 2018 07;13(13):1303-1307
In Vivo Biotinylation of Antigens in E. coli. Gräslund S, Savitsky P, Müller-Knapp S Methods Mol Biol 2017 ;1586():337-344
Antibody Validation by Immunoprecipitation Followed by Mass Spectrometry Analysis. Persson H, Preger C, Marcon E, Lengqvist J, Gräslund S Methods Mol Biol 2017;1575():175-187