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

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.

工作说明书 Sears 博士将担任该 Atlas 基金组织表征核心的联合领导者，与 Ken Lau 博士（范德比尔特）。西尔斯博士和她的实验室将提供技术和分析 人类结肠组织生物膜检测方面的专业知识。西尔斯实验室将培训成员 组织表征核心在结肠生物膜检测中的应用，并将独立用于 培训完成后，读取并验证结肠组织样本的子集。本次验证 交叉检查过程将在整个资助期内持续进行。进一步，西尔斯博士和 她的实验室将参与研究结肠的关系和贡献 生物膜形成到早期结肠癌发生。这一目标将通过两个核心目标来实现： 1) 确定结肠腺瘤中生物膜形成的流行病学； 2）定义变化 生物膜阳性与生物膜阴性腺瘤中的单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本中细胞的类型、数量和位置的专家。他 已发表关于 MANAFEST 检测的文章，该检测在本年第 5 年作为概念验证提出 应用。他将协助刘医生收集和处理血液和患者组织 用于 MANAFEST 检测，如本 Atlas 资助的第 5 年所述。材料加工完成后 将从范德比尔特运往奥尔斯。安德斯的实验室将帮助研究外显子组 肿瘤组织测序、肿瘤浸润的定量和表征 淋巴细胞和 T 细胞增殖测定中涉及的湿化学。 1. 刘实验室将对人体组织进行 scRNA-seq 并提供数据。 2. 刘实验室将对人体组织进行空间转录组学并提供数据。 3. 刘实验室将对人体组织进行外显子组和基因组测序，并提供 数据。 4. 刘实验室将与其他中心协调，对 冒号。

项目成果

Statistical Analysis of Multiplex Immunofluorescence and Immunohistochemistry Imaging Data.

多重免疫荧光和免疫组织化学成像数据的统计分析。

• 发表时间: 2023
• 作者: Wrobel, Julia;Harris, Coleman;Vandekar, Simon
• 通讯作者: Vandekar, Simon