Generation of Unique Type 2 Innate Lymphoid Cell Gene Signature in Nasal Polyposis

Project: Research project

Project Details

Description

The collaboration work plan will focus on RNA sequencing/epigenomics of isolated, purified human type 2 ILCs derived from nasal polyp tissue to identify novel targets amenable for the development of small molecule antagonists or biologic agents. Human ILC2 cells will be subjected to RNASeq and potentially epigenetic analyses. The projected epigenomic approaches that may be utilized on these samples include 1) chromatin immunoprecipitation followed by DNA sequencing (ChIPSeq) to identify enhancer regions, and 2) microRNA and long non-coding RNA expression profiles associated with ILC2 cells present in normal or diseased human mucosal tissues. The use of proteomic technologies such as Somalogics aptamer binding studies and mass spectroscopy will be supplementary and may be used to confirm the RNA and DNA findings. The Principal Investigator will obtain nasal polyp tissue from surgeries and isolate ILC2 cells. In addition to basal gene signatures of ILC2 cells, some samples may be treated with IL-33 or IL-33 plus thymic stromal lymphopoietin (TSLP). The Principal Investigator will provide RNA from these cells to Janssen for molecular profiling activities (RNA sequencing, epigenomics, proteomics). In addition, establishment of human ILC2 in vitro organ tissue assays to monitor the function of these cells will be conducted and the assay methodology may be transferred to Janssen for subsequent use. The production of IL-5 and IL-13 from organ cultures or isolated, purified ILC2 cells will be monitored as endpoints of altered ILC2 function. Some of the studies may include treatment of the organ cultures with molecules of interest that may inform drug discovery approaches. Janssen will work directly with the Principal Investigator to develop the methodology for enrichment of human ILC2 cells using information gained from interactions with CROs and/or in-house resources before purification using cell sorting in the Principal Investigator’s laboratory.
StatusFinished
Effective start/end date3/23/15 → 12/31/16

Funding

  • Janssen Research & Development, LLC (Agmt 03/23/15)

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