Project description:Etrolizumab, a humanized monoclonal antibody that selectively binds the b7 subunit of the heterodimeric integrins a4b7 and aEb7, is currently in development for patients with moderate-to-severely active UC. Integrin aE forms a heterodimer with b7; and aEb7 interacts with E-cadherin to mediate retention of aEb7+ cells in the intestinal epithelium. Baseline integrin aE levels have been identified as a potential predictive biomarker for etrolizumab response. Additional markers, including granzyme A, have also been identified and are being developed in partnership with Roche Molecular as potential predictive biomarkers for etrolizumab along with integrin aE. Extensive work has been done to characterize gut aE+ T cells by immunohistochemistry, flow cytometry and qPCR. We hope to use this project to validate differences between aE+ and aE- cell populations using CD4, CD8 and granzyme A expression as controls. The results from this project will be used to pilot single cell sequencing of CD3+aE+ cells isolated from the gut mucosa to identify cellular heterogeneity within aE+ cells under normal and inflammatory conditions. Materials and methods: Mucosal lymphocytes were isolated using a collagenase digestion from surgical specimens taken during routine gastrointestinal resections of diverticulitis and ulcerative colitis patients. CD45+TCRab+TCRgd- cells were sorted into aE+ and aE- groups.

2021-07-23 | GSE152320 | GEO

Allergen sensitization stratifies IL-31 production by memory T cells in atopic dermatitis patients.

Project description:The role of allergen sensitization in IL-31 production by T cells and specifically in the clinical context of atopic dermatitis (AD) has not been characterized. The response to house dust mite (HDM) in purified memory T cells cocultured with epidermal cells from AD patients (n=58) and control subjects (n=11) was evaluated. AD-associated cytokines from culture supernatants, plasma proteins and mRNA expression from cutaneous lesions were assessed and related with the clinical features of the patients. HDM-induced IL-31 production by memory T cells defined two subsets of AD patients according to the presence or absence of IL-31 response. Patients in the IL-31 producing group showed a more inflammatory profile, and increased HDM-specific (sp) and total IgE levels compared to the IL-31 non-producing group. A correlation between IL-31 production and patient’s pruritus intensity, plasma CCL27 and periostin was detected. When the same patients were analyzed based on HDM-specific (sp) IgE and total IgE levels, an increased IL-31 in vitro response, as well as type 2 markers in plasma and cutaneous lesions, was found in patients with sp IgE levels > 100 kUA/L and total IgE levels > 1000 kU/L. The IL-31 response by memory T cells was restricted to the cutaneous lymphocyte-associated antigen (CLA)+ T-cell subset. IgE sensitization to HDM allows stratifying IL-31 production by memory T cells in AD patients and relating it to particular clinical phenotypes of the disease.

2023-03-06 | GSE226073 | GEO

TAF1 is critical for AE driven leukemogenesis [ATAC-seq]

Project description:TAF1 is essential for AE driven leukemogenesis. Depletion of TAF1 impairs the recruitment of AE to its target genes, interfereing with its control of gene expression. The bromodomains of TAF1 associate with K43 acetylated AE and this association plays a role in the proliferationof AE expressing AML cells.

2019-09-11 | GSE134018 | GEO

TAF1 is critical for AE driven leukemogenesis [RNA-seq]

Project description:TAF1 is essential for AE driven leukemogenesis. Depletion of TAF1 impairs the recruitment of AE to its target genes, interfering with its control of gene expression. The bromodomains of TAF1 associate with K43 acetylated AE and this association plays a role in the proliferation of AE expressing AML cells.

2019-09-11 | GSE115121 | GEO

TAF1 is critical for AE driven leukemogenesis [ChIP-seq]

2019-09-11 | GSE115115 | GEO

Corynebacterium pseudotuberculosis 31 strain:31

Project description:Corynebacterium pseudotuberculosis 31 strain:31 Genome sequencing

| PRJNA73223 | ENA

Sequencing Caenorhabditis sp. 31

Project description:Sequencing Caenorhabditis sp. 31

| PRJEB12600 | ENA