Dr. Samantha Brugmann, PhD

Harnessing the Therapeutic Potential of Neural Crest Cells by Manipulating the Primary Cilium

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, are not 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 Dr. Brugmann’s 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, the lab is 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 treatment of CFAs and ciliopathies.