Research group Michael Sundström
The SGC Karolinska laboratory focus on exploring novel target biology for future drug development in 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 open science. We work on i) patient derived cell assays ii) generating recombinant proteins and antibodies and iii) identification and validation of chemogenomic tool compounds.
Early drug discovery research in chronic inflammatory diseases
The SGC Karolinska laboratory, under the direction of Prof. Michael Sundström, is housed within the Department of Medicine, Solna at Karolinska Institutet (KI), and located at the Centre for Molecular Medicine (CMM).
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.
Members
Michael Sundström
Senior lab manager/Research leader.- Oliver Arnolds, postdoc
- Kristina Edfeldt, research coordinator
- Opher Gileadi, team leader
- Ali Hazrat, IT-technician
- Mohammad Ali Okhovat, PhD student
- Mingmei Shang, research coordinator
- Sonia Youhanna, postdoc
- Kang-cheng Liu, postdoc
EUbOPEN – Enabling and Unlocking Biology in the Open
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/
The 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.
Cooperation
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/
Research support
- 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].
Selected publications
Cellular shape reinforces niche to stem cell signaling in the small intestine.
Pentinmikko N, Lozano R, Scharaw S, Andersson S, Englund JI, Castillo-Azofeifa D, Gallagher A, Broberg M, Song KY, Sola Carvajal A, Speidel AT, Sundstrom M, Allbritton N, Stevens MM, Klein OD, Teixeira A, Katajisto P
Sci Adv 2022 Oct;8(41):eabm1847
Circulating Levels of Interferon Regulatory Factor-5 Associates With Subgroups of Systemic Lupus Erythematosus Patients.
Idborg H, Zandian A, Ossipova E, Wigren E, Preger C, Mobarrez F, Checa A, Sohrabian A, Pucholt P, Sandling JK, Fernandes-Cerqueira C, Rönnelid J, Oke V, Grosso G, Kvarnström M, Larsson A, Wheelock CE, Syvänen AC, Rönnblom L, Kultima K, Persson H, Gräslund S, Gunnarsson I, Nilsson P, Svenungsson E, Jakobsson PJ
Front Immunol 2019 ;10():1029
Generation and validation of recombinant antibodies to study human aminoacyl-tRNA synthetases.
Preger C, Wigren E, Ossipova E, Marks C, Lengqvist J, Hofström C, Andersson O, Jakobsson PJ, Gräslund S, Persson H
J Biol Chem 2020 Oct;295(41):13981-13993
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, Grönwall C, Wermeling F, Gunnarsson I, Lundberg IE, Sundström M, Jakobsson PJ, Berg L
Transl Res 2021 Mar;229():69-82
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, Jakobsson PJ, Berg L
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, Sanniti A, Lledó Lara A, Kasela S, De Cesco S, Wegner JK, Handunnetthi L, McCann FE, Chen L, Sekine T, Brennan PE, Marsden BD, Damerell D, O'Callaghan CA, Bountra C, Bowness P, Sundström Y, Milani L, Berg L, Göhlmann HW, Peeters PJ, Fairfax BP, Sundström M, Knight JC
Nat Genet 2019 Jul;51(7):1082-1091
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, Lundberg IE, Lundström SL
Sci Rep 2018 Dec;8(1):17958
Preclinical target validation using patient-derived cells.
Edwards AM, Arrowsmith CH, Bountra C, Bunnage ME, Feldmann M, Knight JC, Patel DD, Prinos P, Taylor MD, Sundström M,
Nat Rev Drug Discov 2015 Mar;14(3):149-50
Recently targeted kinases and their inhibitors-the path to clinical trials.
Knapp S, Sundström M
Curr Opin Pharmacol 2014 Aug;17():58-63
Crystal structures of histone demethylase JMJD2A reveal basis for substrate specificity.
Ng SS, Kavanagh KL, McDonough MA, Butler D, Pilka ES, Lienard BM, Bray JE, Savitsky P, Gileadi O, von Delft F, Rose NR, Offer J, Scheinost JC, Borowski T, Sundstrom M, Schofield CJ, Oppermann U
Nature 2007 Jul;448(7149):87-91