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.

Public Health Relevance

Diseases that impact facial development are difficult to repair because a large source of skeletal tissue is often necessary. Our research program studies the cells that give rise to the facial skeleton (neural crest cells) and tries to direct their differentiation into skeletal tissues amenable for surgical repair.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Unknown (R35)
Project #
5R35DE027557-04
Application #
9951029
Study Section
Special Emphasis Panel (ZDE1)
Program Officer
Stein, Kathryn K
Project Start
2017-09-14
Project End
2025-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
Elliott, Kelsey H; Brugmann, Samantha A (2018) Sending mixed signals: Cilia-dependent signaling during development and disease. Dev Biol :