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Expression data from skin of patients with adverse drug reactions (ADRs)

ABSTRACT: Expression data from skin of patients with adverse drug reactions (ADRs)

PROVIDER: PRJNA497293 | ENA |

REPOSITORIES: ENA

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Expression data from skin of patients with adverse drug reactions (ADRs)

Project description:ADRs are immune mediated skin reactions of diverse severity and etiology. The patho-mechanisms are however not well understood. We used a gene expression array for the comparison of the gene expression profile of 2 cutaneous adverse drug reactions (MPR and AGEP) to normal skin.

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Multiomic single-cell sequencing of skin and blister fluid from patients with severe cutaneous adverse drug reactions.

Project description:Severe cutaneous adverse reactions (SCAR) are rare but life-threatening drug reactions mediated by human leukocyte antigen (HLA) class I-restricted CD8+ T-cells. To obtain an unbiased assessment of SCAR cellular immunopathogenesis, we performed single-cell (sc) transcriptome, surface proteome, and TCR sequencing (5' scRNA-TCR-CITE-seq, 10x Genomics) on unaffected skin, affected skin, and blister fluid from diverse SCAR patients.

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Gene expression profile at the single-cell level of skin and PBMC samples collected from patients with severe cutaneous adverse drug reactions (SCADR).

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Gene expression profile at the single-cell level of skin and PBMC samples collected from patients with severe cutaneous adverse drug reactions (SCADR).

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GPCR signaling neighborhoods associate with the susceptibility to adverse drug reactions of incretin mimetics

Project description:G protein-coupled receptors are important drug targets that engage and activate signaling transducers in multiple cellular compartments. Delineating therapeutic signaling from signaling associated with adverse events is an important step towards rational drug design. The glucagon-like peptide-1 receptor (GLP-1R) is a validated target for the treatment of diabetes and obesity, but drugs that target this receptor are a frequent cause of adverse events. Using recently developed biosensors, we explored the ability of GLP-1R to activate 15 pathways in 4 cellular compartments and demonstrate that modifications aimed at improving the therapeutic potential of GLP-1R agonists greatly influence compound efficacy, potency and safety in a pathway- and compartment-selective manner. These findings, together with comparative structure analysis, time-lapse microscopy and phosphoproteomics, reveal unique signaling signatures for GLP-1R agonists at the level of receptor conformation, functional selectivity and location bias, thus associating signaling neighborhoods with functionally distinct cellular outcomes and clinical consequences.

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