Harnessing the therapeutic potential of neural crest cells by manipulating the primary cilium

通过操纵初级纤毛来利用神经嵴细胞的治疗潜力

• 批准号: 10661606
• 负责人: Samantha A Brugmann
• 金额: $ 92.23万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 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/10661606
• 关键词: Allografting; Biochemical; Bone Transplantation; Cell Differentiation process; Cell Proliferation; Cells; Cilia; Congenital Abnormality; Craniofacial Abnormalities; Development; Disease; Embryo; Face; Goals; Knowledge; Laboratories; Molecular; Nature; Neural Crest Cell; Operative Surgical Procedures; Organelles; Population; Research; Signal Transduction; Skeleton; Source; Therapeutic; Tissue Engineering; Tissues; United States; Work; bone; ciliopathy; craniofacial repair; neuromechanism; novel therapeutic intervention; novel therapeutics; postnatal; programs; repaired; skeletal tissue

ABSTRACT: Craniofacial anomalies (CFAs) comprise 75% of congenital defects and represent a biomedical burden of almost 700 million dollars per year in the United States. Surgical repair of CFAs is difficult and often requires a large source of skeletal tissue to replace/reconstruct the facial skeleton. Bone grafts used to repair CFAs frequently fail to integrate and are commonly allografts from mesodermally derived bone. This is a suboptimal tissue source since the facial skeleton is embryonically derived from an entirely different population of cells called neural crest cells (NCCs). NCCs; however, have not been used in tissue engineering approaches because a robust, postnatal source of cells does not exist and their multipotent nature raises concerns of regarding uncontrolled differentiation. The over-arching, long-term goal of my laboratory is to integrate our understanding of the cellular, molecular and biochemical mechanisms of NCC development and apply this knowledge towards generating novel therapeutic strategies for generating a robust source of NCC-derived tissues amenable for the surgical repair of craniofacial anomalies. To achieve this goal, we are focusing on precisely directing NCCs proliferation and differentiation into skeletal tissue via manipulation of the primary cilia, the cellular organelle which functions as the signaling hub of all cells. Gaining a firm understanding of how the primary cilia work to transduce molecular signals in NCCs, and other cells, will likely identify several novel therapeutic options for disease treatment. The impact of our work would be broad and far-reaching as it has the potential to revolutionize how CFAs and ciliopathies are treated.

文摘:

项目成果

Centriolar Protein C2cd3 Is Required for Craniofacial Development.

• DOI: 10.3389/fcell.2021.647391
• 发表时间: 2021
• 期刊: Frontiers in cell and developmental biology
• 影响因子: 5.5
• 作者: Chang CF;Brown KM;Yang Y;Brugmann SA
• 通讯作者: Brugmann SA

Mutation in the Ciliary Protein C2CD3 Reveals Organ-Specific Mechanisms of Hedgehog Signal Transduction in Avian Embryos.

• DOI: 10.3390/jdb9020012
• 发表时间: 2021-03-25
• 期刊: Journal of developmental biology
• 影响因子: 2.7
• 作者: Brooks EC;Bonatto Paese CL;Carroll AH;Struve JN;Nagy N;Brugmann SA
• 通讯作者: Brugmann SA

Pharmacological intervention of the FGF-PTH axis as a potential therapeutic for craniofacial ciliopathies.

• DOI: 10.1242/dmm.049611
• 发表时间: 2022-08-01
• 期刊: Disease models & mechanisms
• 影响因子: 4.3

The Society for Craniofacial Genetics and Developmental Biology 44th Annual Meeting.

颅面遗传学和发育生物学学会第 44 届年会。

• DOI: 10.1002/ajmg.a.62731
• 发表时间: 2022
• 期刊: American journal of medical genetics. Part A
• 作者: Brugmann,SamanthaA;Merrill,AmyE;Saint-Jeannet,Jean-Pierre;Stottmann,RolfW;Clouthier,DavidE
• 通讯作者: Clouthier,DavidE

Atavisms in the avian hindlimb and early developmental polarity of the limb.

• DOI: 10.1002/dvdy.318
• 发表时间: 2021-09
• 期刊: Developmental dynamics : an official publication of the American Association of Anatomists
• 作者: Bonatto Paese CL;Hawkins MB;Brugmann SA;Harris MP
• 通讯作者: Harris MP