Mustafa Khokha, MD

My laboratory is interested in the problem of birth defects that occur when embryonic patterning fails to occur properly. A fertilized egg must activate a complex genetic program in order to form functional adult structures. Failure to do so correctly leads to congenital malformations in children, the main cause of infant mortality in the US. We are particularly interested in cellular signals and transcriptional regulation that lead to particular fate changes that specify new tissue types during development. We are also interested in morphogenesis that provides shape to the developing embryo.

Our main approach is to analyze genes identified in infants and children that have birth defects.

We focus on Xenopus as a model system because it is the most closely related human model that is easily and rapidly manipulated. Also there are many congenital malformation genes to analyze and the low cost of Xenopus allows us to study many of these genes by engaging in high-throughput screens. Our main focus is:

• Analysis of human mutations using Xenopus We have identified a number of genes that are mutated in patients that have congenital heart disease, a failure to properly pattern the heart. We have validated a number of these genes by showing that they also cause abnormal development of frog hearts and are now analyzing the mechanisms of their development. Many of these genes are novel and identifying their mechanisms of cardiac morphogenesis will lead to new understanding of congenital malformations and the underlying developmental biology. We are looking to expand to other organ systems as well including the patterning of the face and other organ systems.