A5003193594- Tryptophan and brain disorders
- Atherosclerosis and Cardiovascular Diseases
- Stress Responses and Cortisol
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Receptor Mechanisms and Signaling
- Photodynamic Therapy Research Studies
- Cholesterol and Lipid Metabolism
- Cell Adhesion Molecules Research
- Peptidase Inhibition and Analysis
- Immune cells in cancer
- MicroRNA in disease regulation
- Immune Cell Function and Interaction
- Cardiovascular Disease and Adiposity
- Metabolism and Genetic Disorders
- Click Chemistry and Applications
- CAR-T cell therapy research
- Alzheimer's disease research and treatments
- Hormonal and reproductive studies
- Liver Disease and Transplantation
- Mosquito-borne diseases and control
- Fatty Acid Research and Health
- Monoclonal and Polyclonal Antibodies Research
- Lipoproteins and Cardiovascular Health
- Protease and Inhibitor Mechanisms
Karolinska Institutet
2015-2025
Karolinska University Hospital
2014-2023
Novo Nordisk Foundation
2021
Foundation Center
2021
MorphoSys (Germany)
2019
4SC (Germany)
2017
Bavarian Nordic (Germany)
2009-2016
Medical University of Vienna
2012-2015
Lead Discovery Center (Germany)
2012
University of Vienna
2010
In addition to enhanced proinflammatory signaling, impaired resolution of vascular inflammation plays a key role in atherosclerosis. Proresolving lipid mediators formed through the 12/15 lipoxygenase pathways exert protective effects against murine n-3 Polyunsaturated fatty acids, including eicosapentaenoic acid (EPA), serve as substrate for formation mediators, which transduce potent anti-inflammatory and proresolving actions their cognate G-protein-coupled receptors. The aim this study was...
Recent studies have revealed a close connection between cellular metabolism and the chronic inflammatory process of atherosclerosis. While link systemic atherosclerosis is well established, implications altered in artery wall are less understood. Pyruvate dehydrogenase kinase (PDK)-dependent inhibition pyruvate (PDH) has been identified as major metabolic step regulating inflammation. Whether PDK/PDH axis plays role vascular inflammation atherosclerotic cardiovascular disease remains unclear.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with particularly dismal prognosis. Histone deacetylases (HDAC) are epigenetic modulators whose activity frequently deregulated in various cancers including PDAC. In particular, class-I HDACs (HDAC 1, 2, 3 and 8) have been shown to play an important role this study, we investigated the effects of class I-specific HDAC inhibitor (HDACi) 4SC-202 multiple PDAC cell lines promoting tumor differentiation. We show that...
Atherosclerosis is a chronic inflammatory disease that initiated by the retention and accumulation of low-density lipoprotein in artery, leading to maladaptive response cells from immune system vessel wall. Strong evidence implicates indoleamine 2,3-dioxygenase (IDO), first rate-limiting enzyme kynurenine pathway tryptophan (Trp) degradation, with regulation anti-inflammatory mechanisms different diseases. However, role IDO endogenous degradation Trp have never been directly examined...
Summary Circulating plasma microvesicles (PMVs) and their microRNA content are involved in the development of atherosclerosis could serve as biomarkers for cardiovascular disease (CVD) progression. However, little is known on how smoking influences levels PMVs signatures vivo. Therefore, we aimed to investigate effects circulating PMV CVD-related PMV-derived microRNAs young, healthy smokers. Twenty young (10 female, 10 male; 25 ± 4 years) smokers (16 6 cigarettes per day 8 age- sex-matched...
Abstract Kynurenine pathway (KP) activation by the enzymatic activity of indoleamine 2,3-dioxygenase1 (IDO1) and kynurenine (KYN) production represents an attractive target for reducing tumour progression improving anti-tumour immunity in multiple cancers. However, immunomodulatory properties other KP metabolites such as 3-hydroxy (3-HK) kynurenic acid (KYNA) are poorly understood. The association metabolic with T-cell status microenvironment were characterized, using gene expression data...
Background: Atherosclerosis progression is modulated by interactions with the adaptive immune system. Humoral immunity can help protect against atherosclerosis formation; however, existence, origin, and function of putative atherogenic antibodies are controversial. How such atherosclerosis-promoting could affect specific composition stability plaques, as well vasculature generally, remains unknown. Methods: We addressed overall contribution to plaque formation, composition, in vivo (1) mice...
Radiotherapy-induced cardiovascular disease is an emerging problem in a growing population of cancer survivors where traditional treatments, such as anti-platelet and lipid-lowering drugs, have limited benefits. The aim the study was to investigate vascular inflammatory patterns human survivors, replicate findings animal model, evaluate whether interleukin-1 (IL-1) inhibition could be potential treatment.Irradiated arterial biopsies were collected during microvascular autologous free tissue...
Abstract Background The metabolism of tryptophan (Trp) along the kynurenine pathway has been shown to carry strong immunoregulatory properties. Several experimental studies indicate that this is a major regulator vascular inflammation and influences atherogenesis. Knowledge role in human atherosclerosis remains incomplete. Objectives In study, we performed multiplatform analysis tissue samples, vitro vivo functional assays elucidate potential atherosclerosis. Methods results Comparison...
Atherosclerosis is a chronic inflammatory disease involving immunological and metabolic processes. Metabolism of tryptophan (Trp) via the kynurenine pathway has shown immunomodulatory properties ability to modulate atherosclerosis. We identified 3-hydroxyanthranilic acid (3-HAA) as key metabolite Trp modulating vascular inflammation lipid metabolism. The molecular mechanisms driven by 3-HAA in atherosclerosis have not been completely elucidated. In this study, we investigated whether two...
T-cell activation is characteristic during the development of atherosclerosis. While overall responses have been implicated in disease acceleration, regulatory T cells (Tregs) exhibit atheroprotective effects. The expression enzyme indoleamine 2,3-dioxygenase-1 (IDO), which catalyzes degradation tryptophan (Trp) along kynurenine pathway, has induction and expansion Treg populations. Hence, Tregs can reciprocally promote IDO dendritic via reverse signaling mechanisms antigen presentation. In...
Alzheimer's disease (AD), a multifactorial neurodegenerative condition caused by genetic and environmental factors, is diagnosed using neuropsychological tests brain imaging; molecular diagnostics are not routinely applied. Studies have identified AD-specific cerebrospinal fluid (CSF) biomarkers but sample collection requires invasive lumbar puncture. To identify AD-modulated proteins in easily accessible blood platelets, which share biochemical signatures with neurons, we compared platelet...
Toll-like receptor (TLR)-mediated signaling is proposed as an immunotherapeutic target against tumorigenesis. Natural killer (NK) cells play a critical role in host defense tumors. Specifically, formation of tumor metastasis various organs can be suppressed by the local activity NK cells. In this study, we present novel TLR7 agonist (termed SC-1) that induces pro-inflammatory cytokines human blood cells, activates cell function, and highly efficient preventing lung metastases pulmonary...
Immunotherapy approaches targeting the PD-1 pathway have shown some clinical benefits in a fraction of patients with lung cancer, but expression PD-L1 has proven to be an imperfect biomarker efficacy.Recent studies that tumor mutation burden (TMB) is also correlated outcome and it appears independent PD-L1.TMB, however, only indirectly measures number neoantigenic peptides presented on cell surface class I MHC predicted matches may even better predictor benefit.In addition, mutations genes...
Chronic inflammation is a hallmark of atherosclerosis and results from an imbalance between proinflammatory proresolving signaling. The human GPR32 receptor, together with the ALX/FPR2 transduces biological actions several mediators that stimulate resolution inflammation. However, since no murine homologs receptor exist, comprehensive in vivo studies are lacking. Using atherosclerotic lesions carotid endarterectomies creating transgenic mouse model expressing on Fpr2×ApoE double-KO...
Proprotein convertase subtilisins/kexins (PCSKs) have been implicated in cancers and cardiovascular disease. We shown that PCSK6 is a key protease regulating smooth muscle cell (SMC)-mediated vascular remodeling, but also it can be expressed by T cells macrophages atherosclerotic plaques. Whether regulates innate adaptive immune responses the context of inflammation still unknown. In this study, detailed immunophenotyping constitutive Pcsk6-/- mice was performed. Bone marrow transplantation...
Toll-like receptor 7 (TLR7) agonists are potent immune stimulants able to overcome cancer-associated suppression. Due dose-limiting systemic toxicities, only the topically applied TLR7 agonist (imiquimod) has been approved for therapy of skin tumors. There is a need TLR7-activating compounds with equivalent efficacy but less toxicity. SC1, novel small molecule TLR7, type-1 interferon inducer, comparable reference resiquimod, yet lower induction proinflammatory cytokines. In vivo, SC1...
Abstract CRISPR-Cas12a systems are becoming an attractive genome editing tool for cell engineering due to their broader capabilities compared CRISPR-Cas9 counterparts. As opposed Cas9, the Cas12a endonucleases characterized by a lack of trans-activating crRNA (tracrRNA), which reduces complexity system and simultaneously makes CRISPR RNA (crRNA) promising approach toward further improving modulating activity systems. Here, we design validate sixteen types structurally engineered crRNAs...
Abstract Severe malaria is a life-threatening complication of an infection with the protozoan parasite Plasmodium falciparum , which requires immediate treatment. Safety and efficacy concerns currently used drugs accentuate need for new chemotherapeutic options against severe malaria. Here we describe medicinal chemistry program starting from amicarbalide that led to two compounds optimized pharmacological antiparasitic properties. SC81458 clinical development candidate, SC83288, are...