Progenitor Regulation in Craniofacial Development and Regeneration

颅面发育和再生中的祖细胞调节

• 批准号: 10840025
• 负责人: Gage D Crump
• 金额: $ 7.46万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-14 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10840025
• 关键词: Adult; Affect; Arthritis; Award; California; Cartilage; Cells; Congenital Abnormality; Development; Disease; Doctor of Philosophy; Economics; Face; Faculty; Fellowship; Fishes; Funding; Future; Genes; Genetic; Genetic Techniques; Goals; Head; Human; Image; Imaging Techniques; Industry; Injury; Jaw; Joints; Knowledge acquisition; Maintenance; Mentors; Microscopy; Modeling; Mus; National Institute of Dental and Craniofacial Research; Natural regeneration; Patients; Pattern; Population; Positioning Attribute; Postdoctoral Fellow; Privatization; Publishing; Regenerative Medicine; Regulation; Research; Research Personnel; Resources; Role; Science; Signal Transduction; Skeleton; Stem Cell Research; Surgical sutures; Technology; Temporomandibular Joint; Universities; Work; Zebrafish; arthropathies; bone; career; craniofacial; craniofacial development; craniofacial repair; craniofacial tissue; cranium; healing; high school; human model; improved; innovation; man; member; notch protein; novel; progenitor; programs; recruit; regenerative; regenerative approach; repaired; skeletal; skeletal disorder; stem cell biology; stem cells; tenure track; underrepresented minority student

Birth defects of the head and face are common in the human population. Skull injuries and joint disease, in particular affecting the temporomandibular joint of the jaw, are a major economic and societal burden. This proposal is to support the upward trajectory of a mid-career investigator, Dr. Gage Crump, who works at the interface of craniofacial development and stem cell biology. Specifically, he has developed powerful new zebrafish models of human craniofacial birth defects and disease, which are allowing him to unravel the developmental causes of common craniofacial birth defects and, in a bold new direction, to understand mechanisms of stimulating endogenous repair of the adult skull. Dr. Crump is Director of the PhD Program in Development, Stem Cells, and Regenerative Medicine at the University of Southern California and a founding member of the Eli and Edythe Broad Center for Stem Cell Research, a rapidly growing institute directed by Dr. Andrew McMahon with exceptional core resources and recently recruited junior faculty. He is currently PI on three R01's from NIDCR and has published featured articles in Developmental Cell, eLife, Development, and PLoS Genetics on diverse topics ranging from craniofacial development to jawbone repair and arthritis of the jaw. He has built up an exceptional research team, with several trainees receiving K99 and F31 fellowships from NIDCR, as well as prestigious private fellowships. His previous trainees have gone on to tenure-track faculty and industry positions, and postdocs in HHMI-funded labs. He also participates in local and national efforts to recruit under-represented minority students into stem cell science from high school to graduate levels. These efforts are reflected by a USC Mentoring Award to Dr. Crump in 2017. The research program focuses on the roles of progenitor cells in building the facial skeleton and then maintaining and repairing it in the adult. These studies exploit the unique genetic and imaging strengths of zebrafish, combined with its impressive capabilities of natural regeneration as adults. The first program uses new gene editing technology in zebrafish to analyse requirements for novel craniofacial patterning genes in progenitor regulation, as well as to directly image progenitor lineage commitment using time-lapse microscopy. As exemplified by studies of Jagged-Notch signaling from fish to man, efforts to validate zebrafish findings in mouse will be performed in latter years. The second program investigates the stem cell-based maintenance of two types of joints, the sutures of the skull and the synovial jaw joint. The third program builds on innovative models of bone, cartilage, and joint regeneration in the adult zebrafish jaw, as well as a highly collaborative network of basic researchers and clinicians at USC, to understand how different types of endogenous stem cells are activated to repair craniofacial tissues. Completion of these studies will reveal commonalities and differences between the stem cells that build and then maintain and repair the craniofacial skeleton, with foundational knowledge acquired in zebrafish informing future regenerative approaches towards improving skeletal healing in patients.

头部和面部的先天缺陷在人类中很常见。颅骨损伤和关节疾病，在

项目成果

Craniofacial and cardiac defects in chd7 zebrafish mutants mimic CHARGE syndrome.

• DOI: 10.3389/fcell.2022.1030587
• 发表时间: 2022
• 期刊: Frontiers in cell and developmental biology
• 影响因子: 5.5

Tetraspanin18 regulates angiogenesis through VEGFR2 and Notch pathways.

• DOI: 10.1242/bio.050096
• 发表时间: 2021-02-25
• 期刊: Biology open
• 影响因子: 2.4
• 作者: Li GX;Zhang S;Liu R;Singh B;Singh S;Quinn DI;Crump G;Gill PS
• 通讯作者: Gill PS

The Axenfeld-Rieger Syndrome Gene FOXC1 Contributes to Left-Right Patterning.

• DOI: 10.3390/genes12020170
• 发表时间: 2021-01-26
• 期刊: Genes
• 影响因子: 3.5
• 作者: Chrystal PW;French CR;Jean F;Havrylov S;van Baarle S;Peturson AM;Xu P;Crump JG;Pilgrim DB;Lehmann OJ;Waskiewicz AJ
• 通讯作者: Waskiewicz AJ

Gill developmental program in the teleost mandibular arch.

• DOI: 10.7554/elife.78170
• 发表时间: 2022-06-28
• 期刊: eLife
• 影响因子: 7.7
• 作者: Thiruppathy M;Fabian P;Gillis JA;Crump JG
• 通讯作者: Crump JG