Grant: Foundation Grant

We study structural birth defects of the face. Upwards of 3% of children are born with either structural birth defects of the face such as cleft lip or holoprosencephaly or a genetic disease that affects the face. Both types of conditions cause suffering for affected children and their families. Individualized treatment of diseases such as birth defects is a key goal of precision medicine. Variation among individuals produces differences in responses to treatments. To understand birth defects one has to understand the causes of this variation. We aim to understand how genetic influences act through development to produce variation of the face. Ultimately, the goal is use the knowledge gained to alleviate suffering by either preventing birth defects or, when they occur, to offer the most appropriate treatment for each patient. We propose to modulate central pathways of craniofacial development to determine how they and their interactions determine variation in morphology, cellular dynamics and the expression of downstream genes. We employ novel imaging, genetic and analysis methods to integrate multiple datasets for individual embryos in order to study the mechanisms that drive variation. The PIs have a track record of productive collaboration (3 NIH R01 grants, 30 publications, 13 co-supervised trainees) that has been transformative by integrating morphometrics with developmental biology to study the mechanisms for quantitative variation in morphology.