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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.

拟议中的癌症系统生物学中心，将被称为复杂性中心，癌症合作与共同体是系统生物学和癌症生物学共同努力的结果社区在加州尔湾大学（UCI），由两个校园范围的研究代表复杂生物系统中心和UCI癌症研究所。的中心将解决各种基本和根本的问题，癌症系统，以及为什么他们是像他们这样的组织。该中心研究计划的前提是，在复杂的环境中扩散和发展，这些环境被高度选择用于对癌细胞的生长和分化，以及癌细胞的行为只能在管理该控件的设计原则的上下文。如本建议书所述，中心将开展三个协调的、面向团队的研究项目关于背景、合作和社区在癌症发生和发展中的作用。一该项目将利用结肠癌异种移植模型的新观察结果来研究非遗传性实体瘤的异质性，包括其起源及其与肿瘤生长和对治疗的反应的相关性。第二个项目将调查黑色素瘤的细胞起源，试图澄清这种关系。黑色素瘤和良性病变（黑色素细胞痣）之间的关系，活动这项工作将集中在皮肤环境中黑素细胞前体之间的相互作用，并且在促进从良性发展为恶性的条件下。第三个项目将侧重于改善慢性粒细胞白血病（CML）模型及其治疗，考虑相互作用等级谱系、细胞间反馈和动力学之间的联系。这三个项目将联合收割机数学建模、基因组学和动物模型的实验操作。这三个人都将由一个核心设施服务，用于在单细胞水平上研究肿瘤细胞，提供最新的在单细胞基因组学、转录组学和其他技术中。该中心还将支持短期，由教师和学员（研究生和实习生）发起的跨学科试点项目博士后研究员），以及旨在扩大和丰富癌症系统生物学社区在大学内，在更大的科学界，在公众中。最后，该中心将协调其研究和推广活动， 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