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

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.

Grant Number: 5R35DE027557-08
NIH Institute/Center: NIH
Principal Investigator: Samantha Brugmann