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Sandberg, Kristian
Publications (5 of 5) Show all publications
Drobin, K., Assadi, G., Hong, M.-G., Andersson, E., Fredolini, C., Forsström, B., . . . Halfvarson, J. (2019). Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci. Inflammatory Bowel Diseases, 25(2), 306-316
Open this publication in new window or tab >>Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci
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2019 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 25, no 2, p. 306-316Article in journal (Refereed) Published
Abstract [en]

Background: Few studies have investigated the blood proteome of inflammatory bowel disease (IBD). We characterized the serum abundance of proteins encoded at 163 known IBD risk loci and tested these proteins for their biomarker discovery potential.

Methods: Based on the Human Protein Atlas (HPA) antibody availability, 218 proteins from genes mapping at 163 IBD risk loci were selected. Targeted serum protein profiles from 49 Crohn’s disease (CD) patients, 51 ulcerative colitis (UC) patients, and 50 sex- and age-matched healthy individuals were obtained using multiplexed antibody suspension bead array assays. Differences in relative serum abundance levels between disease groups and controls were examined. Replication was attempted for CD-UC comparisons (including disease subtypes) by including 64 additional patients (33 CD and 31 UC). Antibodies targeting a potentially novel risk protein were validated by paired antibodies, Western blot, immuno-capture mass spectrometry, and epitope mapping.

Results: By univariate analysis, 13 proteins mostly related to neutrophil, T-cell, and B-cell activation and function were differentially expressed in IBD patients vs healthy controls, 3 in CD patients vs healthy controls and 2 in UC patients vs healthy controls (q < 0.01). Multivariate analyses further differentiated disease groups from healthy controls and CD subtypes from UC (P < 0.05). Extended characterization of an antibody targeting a novel, discriminative serum marker, the laccase (multicopper oxidoreductase) domain containing 1 (LACC1) protein, provided evidence for antibody on-target specificity.

Conclusions: Using affinity proteomics, we identified a set of IBD-associated serum proteins encoded at IBD risk loci. These candidate proteins hold the potential to be exploited as diagnostic biomarkers of IBD.

Keywords
inflammatory bowel disease, affinity proteomics, LACC1
National Category
Gastroenterology and Hepatology Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-367294 (URN)10.1093/ibd/izy326 (DOI)000462580900020 ()30358838 (PubMedID)
Funder
AstraZenecaSwedish Research Council, VR 2013-3862Swedish Research Council, 2011-2764Knut and Alice Wallenberg FoundationKnowledge FoundationScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

Jochen M. Schwenk, Mauro D’Amato and Jonas Halfvarson contributed equally.

Available from: 2018-11-29 Created: 2018-11-29 Last updated: 2019-04-29Bibliographically approved
Arvidsson, P. I., Sandberg, K. & Sakariassen, K. S. (2017). Institutional profile: the national Swedish academic drug discovery & development platform at SciLifeLab. FUTURE SCIENCE OA, 3(2), Article ID FSO176.
Open this publication in new window or tab >>Institutional profile: the national Swedish academic drug discovery & development platform at SciLifeLab
2017 (English)In: FUTURE SCIENCE OA, ISSN 2056-5623, Vol. 3, no 2, article id FSO176Article in journal (Other (popular science, discussion, etc.)) Published
Abstract [en]

The Science for Life Laboratory Drug Discovery and Development Platform (SciLifeLab DDD) was established in Stockholm and Uppsala, Sweden, in 2014. It is one of ten platforms of the Swedish national SciLifeLab which support projects run by Swedish academic researchers with large-scale technologies for molecular biosciences with a focus on health and environment. SciLifeLab was created by the coordinated effort of four universities in Stockholm and Uppsala: Stockholm University, Karolinska Institutet, KTH Royal Institute of Technology and Uppsala University, and has recently expanded to other Swedish university locations. The primary goal of the SciLifeLab DDD is to support selected academic discovery and development research projects with tools and resources to discover novel lead therapeutics, either molecules or human antibodies. Intellectual property developed with the help of SciLifeLab DDD is wholly owned by the academic research group. The bulk of SciLifeLab DDD's research and service activities are funded from the Swedish state, with only consumables paid by the academic research group through individual grants.

Keywords
academic drug discovery, academic medical research, antibody therapeutics, biopharma, drug development, drug discovery, pharma research, small molecules
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-331950 (URN)10.4155/fsoa-2017-0013 (DOI)000405987900016 ()28670468 (PubMedID)
Available from: 2017-10-23 Created: 2017-10-23 Last updated: 2018-01-13Bibliographically approved
Arvidsson, P. I., Sandberg, K. & Forsberg-Nilsson, K. (2016). Open for collaboration: an academic platform for drug discovery and development at SciLifeLab. Drug Discovery Today, 21(10), 1690-1698
Open this publication in new window or tab >>Open for collaboration: an academic platform for drug discovery and development at SciLifeLab
2016 (English)In: Drug Discovery Today, ISSN 1359-6446, E-ISSN 1878-5832, Vol. 21, no 10, p. 1690-1698Article, review/survey (Refereed) Published
Abstract [en]

The Science for Life Laboratory Drug Discovery and Development (SciLifeLab DDD) platform reaches out to Swedish academia with an industry-standard infrastructure for academic drug discovery, supported by earmarked funds from the Swedish government. In this review, we describe the build-up and operation of the platform, and reflect on our first two years of operation, with the ambition to share learnings and best practice with academic drug discovery centers globally. We also discuss how the Swedish Teacher Exemption Law, an internationally unique aspect of the innovation system, has shaped the operation. Furthermore, we address how this investment in infrastructure and expertise can be utilized to facilitate international collaboration between academia and industry in the best interest of those ultimately benefiting the most from translational pharmaceutical research - the patients.

National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-311790 (URN)10.1016/j.drudis.2016.06.026 (DOI)000386401000014 ()27373760 (PubMedID)
Available from: 2017-01-02 Created: 2017-01-02 Last updated: 2018-01-13Bibliographically approved
Orhan, F., Bhat, M., Sandberg, K., Stahl, S., Piehl, F., Svensson, C., . . . Schwieler, L. (2016). Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll-like Receptor Stimulation in Peripheral Monocytes. Scandinavian Journal of Immunology, 84(5), 262-271
Open this publication in new window or tab >>Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll-like Receptor Stimulation in Peripheral Monocytes
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2016 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 84, no 5, p. 262-271Article in journal (Refereed) Published
Abstract [en]

Tryptophan degradation along the kynurenine pathway is of central importance for the immune function. Toll-like receptors (TLRs), representing the first line of immune defence against pathogens, are expressed in various cell types. The most abundant expression is found on monocytes, macrophages and dendritic cells. The aim of this study was to investigate whether stimulation with different TLR ligands induces the kynurenine pathway in human peripheral monocytes. Cell supernatants were analysed using a liquid chromatography/mass spectrometry to measure kynurenine, kynurenic acid (KYNA), quinolinic acid (QUIN) and tryptophan. Stimulation of TLR-2, TLR-3, TLR-4, TLR-7/8 and TLR-9 was found to induce the production of kynurenine, but only stimulation of TLR-3 increased levels of further downstream metabolites, such as KYNA and QUIN. Stimulation of TLR-1, TLR-5 and TLR-6 did not induce the kynurenine pathway. Taken together, this study provides novel evidence demonstrating that TLR activation induces a pattern of downstream tryptophan degradation along the kynurenine pathway in monocytes. The results of this study may implicate that TLRs can be used as new drug targets for the regulation of aberrant tryptophan metabolism along this pathway, a potential therapeutic strategy that may be of importance in several disorders.

National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-308912 (URN)10.1111/sji.12479 (DOI)000387049300002 ()27607184 (PubMedID)
Funder
Swedish Society for Medical Research (SSMF), 2009-7053 2013-2838The Swedish Brain FoundationSwedish Society of MedicineTorsten Söderbergs stiftelseAstraZenecaThe Karolinska Institutet's Research Foundation
Available from: 2016-12-01 Created: 2016-12-01 Last updated: 2018-01-13Bibliographically approved
Shalaly, N. D., Aneiros, E., Blank, M., Mueller, J., Nyman, E., Blind, M., . . . Sandberg, K. (2015). Positive Modulation of the Glycine Receptor by Means of Glycine Receptor-Binding Aptamers. Journal of Biomolecular Screening, 20(9), 1112-1123
Open this publication in new window or tab >>Positive Modulation of the Glycine Receptor by Means of Glycine Receptor-Binding Aptamers
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2015 (English)In: Journal of Biomolecular Screening, ISSN 1087-0571, E-ISSN 1552-454X, Vol. 20, no 9, p. 1112-1123Article in journal (Refereed) Published
Abstract [en]

According to the gate control theory of pain, the glycine receptors (GlyRs) are putative targets for development of therapeutic analgesics. A possible approach for novel analgesics is to develop a positive modulator of the glycine-activated Cl(-) channels. Unfortunately, there has been limited success in developing drug-like small molecules to study the impact of agonists or positive modulators on GlyRs. Eight RNA aptamers with low nanomolar affinity to GlyRα1 were generated, and their pharmacological properties analyzed. Cytochemistry using fluorescein-labeled aptamers demonstrated GlyRα1-dependent binding to the plasma membrane but also intracellular binding. Using a fluorescent membrane potential assay, we could identify five aptamers to be positive modulators. The positive modulation of one of the aptamers was confirmed by patch-clamp electrophysiology on L(tk) cells expressing GlyRα1 and/or GlyRα1β. This aptamer potentiated whole-cell Cl(-) currents in the presence of low concentrations of glycine. To our knowledge, this is the first demonstration ever of RNA aptamers acting as positive modulators for an ion channel. We believe that these aptamers are unique and valuable tools for further studies of GlyR biology and possibly also as tools for assay development in identifying small-molecule agonists and positive modulators.

National Category
Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-256041 (URN)10.1177/1087057115590575 (DOI)000361605800006 ()26071243 (PubMedID)
Funder
VINNOVA
Available from: 2015-06-22 Created: 2015-06-22 Last updated: 2018-01-11Bibliographically approved
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