Cell migration and wound repair

细胞迁移和伤口修复

• 批准号: 10631883
• 负责人: Anna Huttenlocher
• 金额: $ 66.98万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10631883
• 关键词: Affinity Chromatography; Autoimmune Diseases; Autoimmunity; Award; Biological Models; Cardiovascular Diseases; Cell Communication; Cells; Complex; Cues; Defect; Diabetes Mellitus; Disease; Funding; Gene Expression; Goals; Health; Human; Imaging Device; Immunologic Deficiency Syndromes; Inflammation; Investments; Malignant Neoplasms; Mediating; Metabolism; Molecular; Optics; Pathologic; Process; Research; Research Personnel; Resolution; Ribosomes; Role; Signal Transduction; Tissues; Translating; Work; Wound models; Zebrafish; cell motility; cell type; chronic wound; design; diabetic; genetic manipulation; genome editing; human disease; microorganism interaction; migration; neutrophil; novel therapeutic intervention; repaired; response; tissue repair; transcriptome sequencing; wound healing

ABSTRACT The overall goal of this Maximizing Investigator’s Research award renewal application is to understand the integration of complex signaling networks at both the single cell and multi-cellular level during wound healing. Despite progress in understanding the signals that guide wound repair, there remains a significant gap in understanding how different types of cells communicate to integrate a wound healing response. This gap limits our ability to design new therapeutic strategies for a broad range of human disease including diabetes, cancer, cardiovascular disease and autoimmunity. The overall focus of our research is to understand the basic molecular mechanisms that regulate cell migration and how defects in cell migration contribute to human disease in the context of tissue damage and repair. The optical transparency and ease of genetic manipulation make zebrafish an ideal model system to dissect multi-cellular and tissue interactions during wound repair. During the prior funding period, we invested significant effort in developing new tools for imaging and manipulating cell dynamics, cell guidance cues, metabolism and matrix remodeling during wound healing in both simple and complex wound models. We performed large-scale TRAP (translating ribosomal affinity purification)- RNAseq and identified context- and cell-type specific gene expression changes. Using genome editing we are now poised to uncover new signaling mechanisms and guidance cues that regulate neutrophil reverse migration and inflammation resolution, and influence matrix remodeling during wound healing. Understanding how wound repair is orchestrated and integrated at both the single cell and multi-cellular level, including the role of microbial interactions, in the different types of tissue damage is the focus of our future research. The overall goal of our work is to identify key signaling networks and guidance cues that mediate cell migration during wound repair, dissect how they are altered in pathological conditions and ultimately may be targeted to understand and treat human disease.

摘要

项目成果

Cell Migration Guided by Cell-Cell Contacts in Innate Immunity.

• DOI: 10.1016/j.tcb.2020.11.002
• 发表时间: 2021-03
• 期刊: TRENDS IN CELL BIOLOGY
• 影响因子: 19
• 作者: Miskolci, Veronika;Klemm, Lucas C.;Huttenlocher, Anna
• 通讯作者: Huttenlocher, Anna

Neutrophil derived LTB4 induces macrophage aggregation in response to encapsulated Streptococcus iniae infection.

• DOI: 10.1371/journal.pone.0179574
• 发表时间: 2017
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Vincent WJB;Harvie EA;Sauer JD;Huttenlocher A
• 通讯作者: Huttenlocher A

Neutrophil migration in infection and wound repair: going forward in reverse.

• DOI: 10.1038/nri.2016.49
• 发表时间: 2016-05-27
• 期刊: Nature reviews. Immunology
• 作者: de Oliveira S;Rosowski EE;Huttenlocher A
• 通讯作者: Huttenlocher A

Neutrophil and Macrophage NADPH Oxidase 2 Differentially Control Responses to Inflammation and to Aspergillus fumigatus in Mice.

• DOI: 10.4049/jimmunol.2200543
• 发表时间: 2022-11-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Idol RA;Bhattacharya S;Huang G;Song Z;Huttenlocher A;Keller NP;Dinauer MC
• 通讯作者: Dinauer MC

Rac2 Functions in Both Neutrophils and Macrophages To Mediate Motility and Host Defense in Larval Zebrafish.

• DOI: 10.4049/jimmunol.1600928
• 发表时间: 2016-12-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Rosowski EE;Deng Q;Keller NP;Huttenlocher A
• 通讯作者: Huttenlocher A