A5016701730- Hepatitis C virus research
- interferon and immune responses
- Immune Cell Function and Interaction
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- IL-33, ST2, and ILC Pathways
- Monoclonal and Polyclonal Antibodies Research
- Psoriasis: Treatment and Pathogenesis
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Marine Bivalve and Aquaculture Studies
- Effects and risks of endocrine disrupting chemicals
- T-cell and B-cell Immunology
- Inflammation biomarkers and pathways
- Physiological and biochemical adaptations
- Ion channel regulation and function
- RNA Research and Splicing
- Chronic Lymphocytic Leukemia Research
- Cancer-related gene regulation
- MicroRNA in disease regulation
- RNA regulation and disease
- Bacterial Infections and Vaccines
- Inflammasome and immune disorders
- Congenital gastrointestinal and neural anomalies
- Legionella and Acanthamoeba research
Austrian Academy of Sciences
2022-2025
23andMe (United States)
2024
Yale University
2018-2023
CeMM Research Center for Molecular Medicine
2022
Medical University of Vienna
2022
University of Washington
2013-2020
Seattle University
2013
Abstract Solute carrier (SLC) transporters govern most of the chemical exchange across cellular membranes and are integral to metabolic regulation, which in turn is linked function identity. Despite their key role, individual functions SLC superfamily members were not evaluated systematically. We determined transcriptional profiles upon overexpression knock-out or wild-type isogenic cell backgrounds for 378 SLCs 441 SLCs, respectively. Targeted metabolomics provided a fingerprint 189...
Synthetic oligonucleotides ( ODN ) expressing C p G motifs mimic the ability of bacterial DNA to trigger innate immune system via TLR 9. Plasmacytoid dendritic cells (p DC s) make a critical contribution ensuing response. This work examines induction antiviral IFN ‐β) and pro‐inflammatory IL ‐6) cytokines by ‐stimulated human s CAL ‐1 cell line. Results show that interferon regulatory factor‐5 IRF ‐5) NF ‐κ B p50 are key co‐regulators ‐β ‐6 expression following 9‐mediated activation s. The...
Interferon (IFN) lambdas are critical antiviral effectors in hepatic and mucosal infections. Although IFNλ1, IFNλ2, IFNλ3 act antiviral, genetic association studies have shown that expression of the recently discovered IFNL4 is detrimental to hepatitis C virus (HCV) infection through a yet unknown mechanism. Intriguingly, human harbors variant introduces premature stop codon. We performed molecular biochemical characterization IFNλ4 determine its role regulation expression. found exhibits...
Solute carrier (SLC) transporters govern most of the chemical exchange across cellular membranes and are integral to metabolic regulation, which in turn is linked function identity. Despite their key role, individual functions members SLC superfamily were not evaluated systematically. We determined transcriptional profiles upon overexpression knock-out or wild-type isogenic cell backgrounds. Targeted metabolomics provided a fingerprint 189 intracellular metabolites, while transcriptomics...
Psoriasis pathology is driven by the type 3 cytokines IL-17 and Il-22, but little understood about dynamics that initiate alterations in tissue homeostasis. Here, we use mouse models, single-cell RNA-seq (scRNA-seq), computational inference cell lineage mapping to show psoriasis induction reconfigures functionality of skin-resident ILCs disease. Tissue-resident amplified an initial IL-23 trigger were sufficient, without circulatory ILCs, drive pathology, indicating ILC remodeling initiates...
Eukaryotes have cytosolic surveillance systems to detect invading microorganisms and initiate protective immune responses. In turn, host-adapted pathogens evolved strategies modulate these systems, which can promote dissemination persistence in the host. The obligate intracellular pathogen
Excitatory amino acid transporters (EAAT/SLC1) mediate Na+-dependent uptake of extracellular glutamate and are potential drug targets for neurological disorders. Conventional methods to assess transport in vitro based on radiolabels, fluorescent dyes or electrophysiology, which potentially compromise the cell's physiology generally less suited primary screens. Here, we describe a novel label-free method human EAAT function living cells, i.e., without use chemical modifications substrate...
Abstract Using genome-wide association studies (GWAS) of the 23andMe genetic and healthy survey database across all phenotypes as part our unique target discovery platform, we identified immuno-oncology (I/O)-related variants those with opposing directionality effects on cancer immunological phenotypes, which comprise I/O signature. This signature ULBP6 a potential therapeutic target. is stress-induced cell surface ligand found cells, that binds to activating receptor, NKG2D, NK T cells...
Abstract 23ME-00610 is a monoclonal antibody that being evaluated as single agent in Phase 1/2a clinical trial for advanced solid malignancies (NCT05199272). It binds with high affinity (KD < 0.1 nM) to CD200R1, promising immune-oncology (IO) target identified by surveying the 23andMe genetic and health survey database. CD200R1 an inhibitory receptor when bound its ligand CD200, reduces pro-inflammatory cytokine production, leads immunosuppressive tumor environment. To gain further...
Abstract Hepatitis C virus (HCV) is a hepatotrophic ssRNA that infects over 160 million people worldwide and 60–80% of HCV cases will persist to chronic infection, serious risk factor for liver diseases. We recently discovered infection hepatocytes induces expression two microRNAs (miRNAs), miR-208b miR-499a-5p. found these miRNA are capable decreasing IFNL2 IFNL3 aid viral replication. Here we show miR-499a-5p block type I IFN signaling in HCV-infected by directly targeting down regulating...
Abstract Interferon lambda (IFN-λ) has gained increasing attention recently as an important mediator of antiviral protection in hepatitis C virus (HCV) infection. Similar to many cytokines, we have shown that expression IFNL is regulated on a post-transcriptional level. Interestingly, single nucleotide polymorphisms (SNPs) within the genes dictate outcome acute HCV infection and serve prognostic marker for therapy chronic Previously, demonstrated functional SNP (rs4803217) 3'-untranslated...
Abstract Robust production of type I interferon (IFN) by plasmacytoid dendritic cells (pDCs) occurs in response to Toll-like receptor 9 (TLR9) activation unmethylated CpG dinucleotides present bacterial and viral DNA. Previous work using different oligodeoxynucleotides (ODN) revealed that CpG-A ODN but not CpG-B robustly induce IFN-α pDCs. Although do efficiently IFN-α, they are capable highly inducing IFN-β. However, it is currently unclear what factors mediate induction IFN-β human Using...
Abstract γδ T cells are abundant cell population at the mucosa and important in providing immune surveillance as well maintaining tissue homeostasis. However, despite origin thymus, detailed mechanisms regulating development remain poorly understood. N 6 -methyladenosine (m A) represents one of most common post-transcriptional modifications mRNA mammalian cells, but whether it plays a role biology is still unclear. Here we show that depletion m A demethylase ALKBH5 lymphocytes specifically...
<p>Hypoxia is widely distributed in coastal benthic habitats and driven by warming, nutrient pollution the diurnal cycles of photosynthesis respiration. Benthic sessile species, such as soft shell clam <em>Mya arenaria</em>, are commonly exposed to oxygen fluctuations their which might negatively impact performance metabolism clams. To determine effects different regime on behavior <em>M. we clams for 21 days chronic (constant) hypoxia...