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

结直肠肿瘤转化中宿主和微环境的综合单细胞图谱

• 批准号: 10820067
• 负责人: Robert J. Coffey
• 金额: $ 104.07万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10820067
• 关键词: Address; Atlases; Bacteria; Biological Assay; Biology; Blood; Carcinoma; Cells; Chemistry; Classification; Clinical Data; Collection; Colon; Colonic Adenoma; Colonoscopy; Colorectal; Colorectal Cancer; Colorectal Polyp; Communities; Data; Data Analyses; Data Analytics; Data Collection; Data Set; Detection; Ecosystem; Epidemiology; Epithelial Cells; Excision; Fluorescent in Situ Hybridization; Future; Gene Expression Profile; Goals; Grant; Guidelines; Human; Immunofluorescence Immunologic; Incidence; Injury; Laboratories; Lead; Lesion; Location; Malaysia; Malignant Neoplasms; Medical; Microbial Biofilms; Modeling; Molecular; Neoplastic Cell Transformation; Operative Surgical Procedures; Participant; Patients; Polyps; Precancerous Polyp; Prevention strategy; Process; Proteomics; Publishing; Research; Sampling; Specimen; Standardization; T-Cell Proliferation; Tissues; Training; Tumor Tissue; Tumor-Infiltrating Lymphocytes; Validation; Work; adenoma; analytical tool; base; clinically relevant; colon carcinogenesis; colorectal cancer prevention; data integration; design; epidemiologic data; exome sequencing; exposed human population; genome sequencing; human tissue; improved; member; microbiome; mortality; premalignant; prevent; prospective; risk stratification; sample collection; screening; single-cell RNA sequencing; stem cells; transcriptomics; tumor; Address; Atlases; Bacteria; Biological Assay; Biology; Blood; Carcinoma; Cells; Chemistry; Classification; Clinical Data; Collection; Colon; Colonic Adenoma; Colonoscopy; Colorectal; Colorectal Cancer; Colorectal Polyp; Communities; Data; Data Analyses; Data Analytics; Data Collection; Data Set; Detection; Ecosystem; Epidemiology; Epithelial Cells; Excision; Fluorescent in Situ Hybridization; Future; Gene Expression Profile; Goals; Grant; Guidelines; Human; Immunofluorescence Immunologic; Incidence; Injury; Laboratories; Lead; Lesion; Location; Malaysia; Malignant Neoplasms; Medical; Microbial Biofilms; Modeling; Molecular; Neoplastic Cell Transformation; Operative Surgical Procedures; Participant; Patients; Polyps; Precancerous Polyp; Prevention strategy; Process; Proteomics; Publishing; Research; Sampling; Specimen; Standardization; T-Cell Proliferation; Tissues; Training; Tumor Tissue; Tumor-Infiltrating Lymphocytes; Validation; Work; adenoma; analytical tool; base; clinically relevant; colon carcinogenesis; colorectal cancer prevention; data integration; design; epidemiologic data; exome sequencing; exposed human population; genome sequencing; human tissue; improved; member; microbiome; mortality; premalignant; prevent; prospective; risk stratification; sample collection; screening; single-cell RNA sequencing; stem cells; transcriptomics; tumor

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.

工作声明 Sears博士将成为该地图集的组织表征核心的共同领导者 肯·劳（Ken Lau）博士（范德比尔特（Vanderbilt））。 Sears博士及其实验室将提供技术和分析 人类结肠组织生物膜检测的专业知识。西尔斯实验室将培训成员 结肠生物膜检测中的组织表征核心的核心，并将独立使用 训练完成后，读取并验证结肠组织标本的子集。此验证 在整个赠款期间，交叉检查过程将继续。进一步，西尔斯博士和 她的实验室将参加研究以解决结肠的关系和贡献 生物膜形成早期结肠癌发生。该目标将通过2个核心目的来解决： 1）确定结肠腺瘤中生物膜形成的流行病学； 2）定义更改 生物膜阳性与生物膜阴性腺瘤中的单个上皮细胞表达和蛋白质组学。 将开发用于检测和量化结肠生物膜的临床相关参数。 安德斯博士是定义肿瘤样品中细胞的类型，数量和位置的专家。他 已发表在最多的测定法上，该测定法在此中作为概念证明 应用。他将协助Lau博士收集和处理血液和患者组织 对于该地图集资助的第5年中所述的最多测定法。一旦处理了材料 将从范德比尔特（Vanderbilt）运送到ORS。安德斯的实验室，将帮助外显社 肿瘤组织的测序，肿瘤浸润的定量和表征 淋巴细胞和涉及T细胞增殖测定法的湿化学。 1。LAU实验室将在人体组织上执行SCRNA-SEQ并传递数据。 2。LAU实验室将对人体组织进行空间转录组学并传递数据。 3。劳实验室将对人体组织进行外显子组和基因组测序 数据。 4。LAU实验室将与其他中心进行协调，并在 冒号。