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.
Project description:Evaluation of all human miRNAs in HIV positive and negative individuals. Used to validate RNA extraction from serum. Also used to determine which miRNAs were present in the serum of HIV+ individuals.
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.
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.
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.
Project description:Epidermal keratinocytes were isolated from adult murine skin and FACS sorted into three populations based on their surface maker expression of alpha 6 integrin, CD34 and Sca-1. <br>- Alpha 6 positive cells constitute the entire population of basal or proliferative keratinocytes from the interfollicular epidermis and hair follicle. Both BIB and Bulge cells are contained within the total population of alpha 6 positive cells. <br>- BIB cells reside in the hair follicle in a region between the infundibulum and bulge and these cells are characterized by low alpha 6 integrin surface levels and are negative for CD34 and Sca-1 surface proteins. <br>- Bulge cells are derived from the bulge region of the hair follicle and are characterized by low + high alpha 6 integrin surface levels and are positive for CD34 but negative for Sca-1.