Integrative Single-Cell Atlas of Host and Microenvironment in Colorectal Neoplastic Transformation

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Statement of Work Dr. Sears will be co-leader of the Tissue Characterization Core of this Atlas grant working with Dr. Ken Lau (Vanderbilt). Dr. Sears and her laboratory will provide technical and analytical expertise on biofilm detection on human colon tissues. The Sears laboratory will train members of the Tissue Characterization Core in colon biofilm detection and will serve to independently read and validate a subset of colon tissue specimens once training is complete. This validation and cross-checking process will continue throughout the grant period. Furthery, Dr. Sears and her laboratory will participate in studies to address the relationship and contribution of colon biofilm formation to early colon carcinogenesis. This goal will be addressed through 2 core aims: 1) identifying the epidemiology of biofilm formation in colon adenomas; and 2) defining changes in single epithelial cell expression and proteomics in biofilm-positive vs biofilm-negative adenomas. Clinically relevant parameters for detecting and quantifying colon biofilms will be developed. Dr. Anders is an expert in defining the type, number and location of cells in tumor samples. He has published on the MANAFEST assay which is put forth as a proof of concept in year 5 of this application. He will assist Dr. Lau on the collection and processing of blood and patient tissue for MANAFEST assays as described in year 5 of this Atlas grant. Once processed the material will be shipped from Vanderbilt to Ors. Anders' laboratory who will help with the exome sequencing of the tumor tissue, the quantification and characterization of tumor infiltrating lymphocytes and the wet chemistry involved in the T-cell proliferation assay. 1. The Lau Lab will perform scRNA-seq on human tissues and deliver the data. 2. The Lau Lab will perform spatial transcriptomics on human tissues and deliver the data. 3. The Lau Lab will perform exome and genome sequencing on human tissues and deliver the data. 4. The Lau Lab will coordinate with other centers and conduct trans-atlas analyses on the colon.