Complexity, Cooperation and Community in Cancer

癌症的复杂性、合作和社区

基本信息

批准号：
10392892
负责人：
Arthur D Lander
金额：
$ 187.91万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10392892
关键词：
Address Animal Model Area Basic Science Behavior Benign Biology California Cancer Biology Cancer Center Cells Characteristics Chronic Myeloid Leukemia Colon Carcinoma Colorectal Cancer Communities Complement Complex Comprehensive Cancer Center Computers Core Facility Data Analyses Development Differentiation and Growth Diffusion Engineering Ensure Environment Event Faculty Family Feedback Fostering General Population Genomics Grant Growth Homeostasis Hybrids Image Individual Joints Learning Lesion Mainstreaming Malignant - descriptor Malignant Neoplasms Mathematics Melanocytic nevus Methodology Modeling National Institute of General Medical Sciences Oncogenic Pilot Projects Postdoctoral Fellow Prevention therapy Proliferating Property Regulation Research Research Activity Research Institute Research Personnel Research Project Grants Role Science Scientist Skin Solid Neoplasm Sum System Systems Biology Technology Tissues Training Training Activity Universities Work Xenograft Model Xenograft procedure anticancer research arm cancer cell cancer prevention cancer type cell transformation complex biological systems design genome-wide analysis graduate student improved leukemia mathematical model melanocyte melanoma member neoplastic cell non-genetic novel strategies outreach programs response to injury self organization single cell analysis transcriptomics treatment response tumor growth tumor progression

项目摘要

The proposed Center for Cancer Systems Biology, to be known as the Center for Complexity, Cooperation and Community in Cancer, is a joint effort by the systems biology and cancer biology communities at the University of California Irvine (UCI), as represented by two campus-wide research organizations, the Center for Complex Biological Systems and the UCI Cancer Research Institute. The center will tackle a variety of basic and fundamental questions about cancer systems, and why they are organized as they are. The premise underlying the research program of the center is that cancer cells proliferate and evolve in complex environments that have been highly selected for the robust control of growth and differentiation, and that the behaviors of cancer cells can only be fully understood in the context of the design principles that govern that control. As described in this proposal, the center will carry out three coordinated, team-oriented research projects on the role of context, cooperation and community in the initiation and progression of cancer. One project will leverage new observations from xenograft models of colon cancer to investigate non-genetic heterogeneity in solid tumors, both its origins and its relevance to tumor growth and response to therapy. A second project will investigate the cellular origins of melanoma, seeking to clarify the relationship between melanoma and the benign lesions (melanocytic nevi) that are driven by a common oncogenic event. This work will focus on interactions among melanocyte precursors, within the skin environment, and under conditions that promote progression from benign to malignant. The third project will focus on improving models of chronic myeloid leukemia (CML) and its treatment, taking into account interactions between hierarchical lineages, intercellular feedback, and dynamics. All three projects will combine mathematical modeling, genomics, and experimental manipulation of animal models. All three will be served by a core facility for investigating tumor cells at the single cell level, providing access to the latest in single-cell genomic, transcriptomic and other technologies. The center will also support short-term, interdisciplinary pilot projects initiated both by faculty and by trainees (graduate students and postdoctoral fellows), as well as a wide variety of outreach activities aimed at expanding and enriching the cancer systems biology community both within the university, in the larger scientific community, and among the public. Finally, the center will coordinate its research and outreach activities with those of other centers in the NCI Cancer Systems Biology network.

拟议的癌症系统生物学中心被称为复杂性中心，癌症的合作与社区是系统生物学和癌症生物学的共同努力加利福尼亚大学尔湾分校（UCI）的社区，以两项校园范围的研究为代表组织，复杂生物系统中心和UCI癌症研究所。这中心将解决有关癌症系统的各种基本和基本问题，以及为什么它们是按照他们的井井有条。中心研究计划的前提是癌细胞在高度选择的复杂环境中扩散和进化生长和分化，并且癌细胞的行为只能在控制该控制的设计原则的上下文。如本提案中所述，该中心将进行三个协调的，面向团队的研究项目在背景，合作和社区在癌症的启动和发展中的作用。一项目将利用结肠癌异种移植模型的新观测来研究非遗传实体瘤的异质性，其起源及其与肿瘤生长和对治疗反应的相关性。第二个项目将研究黑色素瘤的细胞起源，试图澄清这种关系在黑色素瘤和良性病变（黑色素细胞NEVI）之间，这些病变由常见的致癌性驱动事件。这项工作将重点介绍黑素细胞前体之间的相互作用，在皮肤环境中，并在促进从良性到恶性发展的条件下。第三个项目将重点放在考虑到相互作用，改善慢性髓样白血病（CML）及其治疗模型在分层谱系，细胞间反馈和动力学之间。这三个项目将结合在一起动物模型的数学建模，基因组学和实验操作。这三个将是由核心设施提供的用于调查单细胞水平的肿瘤细胞，提供最新的访问权限在单细胞基因组，转录组和其他技术中。该中心还将支持短期由教师和学员发起的跨学科试点项目（研究生和博士后研究员）以及旨在扩大和丰富的各种外展活动癌症系统生物学社区都在大学内，更大的科学界和在公众中。最后，该中心将协调其研究和外展活动 NCI癌症系统生物学网络中的其他中心。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Dynamics of nevus development implicate cell cooperation in the growth arrest of transformed melanocytes.

DOI：
10.7554/elife.61026
发表时间：
2020-10-13
期刊：
eLife
影响因子：
7.7
作者：
Ruiz-Vega R;Chen CF;Razzak E;Vasudeva P;Krasieva TB;Shiu J;Caldwell MG;Yan H;Lowengrub J;Ganesan AK;Lander AD
通讯作者：
Lander AD

An in vitro vascularized micro-tumor model of human colorectal cancer recapitulates in vivo responses to standard-of-care therapy.

DOI：
10.1039/d0lc01216e
发表时间：
2021-04-07
期刊：
Lab on a chip
影响因子：
6.1
作者：
Hachey SJ;Movsesyan S;Nguyen QH;Burton-Sojo G;Tankazyan A;Wu J;Hoang T;Zhao D;Wang S;Hatch MM;Celaya E;Gomez S;Chen GT;Davis RT;Nee K;Pervolarakis N;Lawson DA;Kessenbrock K;Lee AP;Lowengrub J;Waterman ML;Hughes CCW
通讯作者：
Hughes CCW

Aspirin's effect on kinetic parameters of cells contributes to its role in reducing incidence of advanced colorectal adenomas, shown by a multiscale computational study.

DOI：
10.7554/elife.71953
发表时间：
2022-04-13
期刊：
ELIFE
影响因子：
7.7
作者：
Wang, Yifan;Boland, C. Richard;Goel, Ajay;Wodarz, Dominik;Komarova, Natalia L.
通讯作者：
Komarova, Natalia L.

Inferring latent temporal progression and regulatory networks from cross-sectional transcriptomic data of cancer samples.

从癌症样本的横截面转录组数据推断潜在的时间进展和调控网络