Progenitor Regulation in Craniofacial Development and Regeneration

颅面发育和再生中的祖细胞调节

• 批准号: 10641883
• 负责人: Gage D Crump
• 金额: $ 106.62万
• 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/10641883
• 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.

头和脸的先天缺陷在人口中很常见。头骨伤害和关节疾病 颌骨的颞下颌关节特别是经济和社会负担。这 提案是为了支持职业中期调查员Gage Crump博士的向上轨迹，他在 颅面发育和干细胞生物学的界面。具体来说，他已经发展了有力的新 人类颅面出生缺陷和疾病的斑马鱼模型，使他能够解散 共同的颅面出生缺陷的发展原因，并以大胆的新方向理解 刺激成年头骨内源性修复的机制。 Crump博士是博士学位课程的主任 南加州大学的开发，干细胞和再生医学和建立 Eli和Edyth Tem细胞研究中心的成员，该研究所是由博士执导的快速成长的研究所 安德鲁·麦克马洪（Andrew McMahon）拥有出色的核心资源，最近招募了初级教师。他目前正在 来自NIDCR的三个R01，并发表了发育细胞，Elife，Development和 关于从颅面发育到颌骨修复和关节炎的各种主题的PLOS遗传学 颚。他建立了一个杰出的研究团队，几名受训人员获得了K99和F31奖学金 来自NIDCR，以及享有声望的私人奖学金。他以前的学员已经去了终身 教职员工和行业职位，以及H​​HMI资助的实验室的博士后。他还参加地方和国家 从高中到研究生的干细胞科学招募人数不足的少数族裔学生的努力 水平。这些努力在2017年授予Crump博士的USC指导奖。 重点关注祖细胞在建造面部骨架中的作用，然后将其维护和修复 成人。这些研究利用了斑马鱼的独特遗传和成像强度，并结合其 成年人自然再生的令人印象深刻的能力。第一个程序使用新的基因编辑技术 在斑马鱼中，分析了祖细胞调节中新型颅面图案基因的要求， 使用延时显微镜直接成像祖细胞谱系承诺。如研究 从鱼到人的锯齿状信号传导，将在鼠标中验证斑马鱼发现的努力。 后期。第二个程序研究了两种关节的基于干细胞的维护， 头骨和滑膜下颌关节的缝合线。第三个程序以骨骼，软骨的创新模型为基础 和成人斑马鱼的联合再生以及基础研究人员的高度协作网络 和南加州大学的临床医生，了解如何激活不同类型的内源性干细胞以修复 颅面组织。这些研究的完成将揭示茎之间的共同点和差异 建立然后维护和修复颅面骨骼的细胞，并获得了基础知识 斑马鱼告知未来再生方法，以改善患者的骨骼愈合。