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Application of Boolean Networks to discover stem and progenitor cells

应用布尔网络发现干细胞和祖细胞

基本信息

批准号：
8919263
负责人：
Debashis Sahoo
金额：
$ 24.15万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8919263
关键词：
B cell differentiation B-Lymphocytes Cancer Model Cell Separation Cells Chin Clinical Collaborations Data Data Set Databases Development Developmental Gene Developmental Process Diagnostic Epithelial Future Gene Expression Genes Goals Health Hematological Disease Hematopoietic stem cells Human Immunocompromised Host Knowledge Laboratories Lymphocyte Malignant Neoplasms Malignant neoplasm of urinary bladder Methods Mining Mission Modeling Mus Natural regeneration Organ Pathway interactions Patients Phase Physicians Play Population Publishing Research Research Infrastructure Research Personnel Resistance Role Scientist Stem cells Survival Analysis Systems Biology T-Cell Development Testing Time Tissue Microarray Tissues Transitional Cell Carcinoma United States United States National Institutes of Health Urothelium Validation Work Xenograft procedure base cancer cell cancer stem cell cancer therapy cancer type combat computerized tools conventional therapy human disease human tissue injured molecular marker neoplastic cell novel novel strategies progenitor prognostic protein expression regenerative stem tool tumor tumor xenograft

项目摘要

Project Summary We have developed several novel approaches for analysis of massively parallel gene expression datasets. First, StepMiner, a tool that identiﬁes step-wise transitions in the time course microarray datasets. Second, BooleanNet, a method of discovering Boolean implications between genes using these large numbers of gene expression datasets. Recently, we published a new method called MiDReG (Mining Developmentally Regulated Genes) that uses Boolean implications to successfully predict genes in developmental pathways. By initially applying this approach to lymphocyte differentitaion, we discovered previously unrecognized markers for B cell differentiation, as well as a novel branchpoint of B cell and T cell development. The proposed project will build on our successful prediction of human B cell developmental genes using MiDReG to develop a general method for discovering cancer stem and progenitor cells. I am planning to validate this approach in human bladder cancer (Transitional Cell Carcinoma), ﬁrst, because it is a simple model cancer to test, and, second, because our laboratory has the expertise to isolate and test cell populations for tumor-initiating potential. This method will be optimized for the discovery of stem and progenitor cells in bladder cancer and hopefully it will serve as a starting point for similar studies in other types of cancers. More than 90% of human bladder cancers arise from a simple epithelial tissue called urothelium, and are commonly called transitional cell carcinomas (TCC). Furthermore, human bladder cancer is ﬁfth most common cancer in the United States. Our laboratory has established a working model for the xenotransplantation of human bladder cancer in mice and has recently discovered a tumor-initiating population in bladder cancer. Recent studies show that cancer is heterogeneous and forms a hierarchy of original tumor cell populations. However, a detailed bladder cancer developmental hierarchy remains unknown. My primary near-term goal in this proposal is to understand this hierarchy of bladder cancer cells using a systems biology approach to predict (diagnostic/prognostic) genes that mark speciﬁc populations. I will validate this approach using human cancer tissue microarrays in collaboration with Dr. Matt van de Rijn ,and using xenotransplantation in collaboration with Drs. Robert Chin and Jens-Peter Volkmer. In the longer term, I will extend the method to identify stem and progenitor cells in other types of cancers during my independent investigator phase.

项目总结