Research Departments & Organizations
Our laboratory is interested in understanding congenital birth defects. Many children are born with various birth defects including defects of the heart, brain, lungs, and face. These birth defects often require surgery and can be difficult to treat for the child. We hope to discover the genes that lead to these birth defects with the hope of improving our understanding of how human development (embryology) occurs.
Extensive Research Description
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 In collaboration with Lifton and Brueckner labs, 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.
|Children's Health, Genetics - Pediatric||YSM Pediatric Critical Illness Patient Registry and Biorepository|
The ribosome biogenesis factor Nol11 is required for optimal rDNA transcription and craniofacial development in Xenopus.
Griffin JN, Sondalle SB, Del Viso F, Baserga SJ, Khokha MK. The ribosome biogenesis factor Nol11 is required for optimal rDNA transcription and craniofacial development in Xenopus. PLoS Genetics 2015, 11:e1005018. 2015
Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation.
Romberg N, Al Moussawi K, Nelson-Williams C, Stiegler AL, Loring E, Choi M, Overton J, Meffre E, Khokha MK, Huttner AJ, West B, Podoltsev NA, Boggon TJ, Kazmierczak BI, Lifton RP. Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation. Nature Genetics 2014, 46:1135-1139. 2014
The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality.
Boskovski MT, Yuan S, Pedersen NB, Goth CK, Makova S, Clausen H, Brueckner M, Khokha MK. The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality. Nature 2013, 504:456-9. 2013
Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning.
Fakhro KA, Choi M, Ware SM, Belmont JW, Towbin JA, Lifton RP, Khokha MK, Brueckner M. Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108:2915-20. 2011