Host research mentor: Michael T. Longaker, M.D.
Stanford University
The Longaker lab is a reconstructive plastic surgery lab focusing on skeletal and epithelial reconstruction and regeneration. I am working with the skeletal biology and bone team, under the guidance of Dr. Natalina Quarto. My project is primarily an investigation into the effects of Twist1 haploinsufficiency on calvarial development and regeneration. In a normal skull, Twist1 is expressed in the mid-sutural mesenchyme. Although Twist1 does not affect the expression of the master osteogenic gene Runx2, it does inhibit transactivation of the gene by binding to the DNA binding motif of Runx2. In short, osteogenesis is a negatively regulated process which is at least partially regulated by Twist1. In haploinsufficient animals, Twist1 expression is not sufficient to successfully inhibit the onset of osteogenesis. This leads to an early ossification of the cranial sutures, called craniosynostosis; in humans this is called Saethre-Chotzen syndrome. Although much is known about how and why this mutation causes abnormal ossification of the sutures, little is understood about the potential effects this may have on calvarial healing. Currently, very few modalities exist for calvarial reconstruction and we hope to further understand the underlying mechanisms through which osteogenesis in the skull is achieved in search of techniques and treatments to meet this biomedical need.