Mustafa Kezar Khokha, MD

Associate Professor of Pediatrics (Critical Care) and of Genetics

Research Interests

Embryo, Nonmammalian; Germ Layers; Notochord; Organizers, Embryonic; Neural Plate

Research Organizations

Animal Organogenesis

Pediatrics: Pediatric Critical Care Medicine

Research Summary

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 embryonic patterning. 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, a significant cause of inherited childhood diseases. 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. We have three approaches to discover these patterning events: 1) genetic screens in Xenopus tropicalis 2) quantitative analysis of Xenopus epidermis to create a coordinated field of cells 3) human genetic studies of children with congenital malformations. We focus on Xenopus as a model system because of the power of the frog system for gain of function and experimental embryology (“cut-and-paste” developmental biology). In addition, we have pioneered X. tropicalis as an amphibian genetic system because of its diploid genome and genomic tools.

  • Analysis of X. tropicalis mutants A number of mutants have been identified in previous genetic screens and additional screens are ongoing. Mutants that have been identified are now being cloned using next-gen sequencing and exon capture arrays. Once cloned, we are using all the power of the Xenopus system to analyze gene function.
  • 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.
  • Quantitative analysis of a field of ciliated cells that create fluid flow Specific cells on the epidermis of the Xenopus embryos are ciliated. These ciliated cells beat in a coordinated fashion to create flow across the entire length of the embryo. How these cells generate flow and sense flow to coordinate their beating remains uncertain. We are using advanced imaging techniques and quantitative biology to better understand how cilia driven flow is established and maintained. In addition, we have identified cilia mutants that have abnormal flow and so combining mutants, morpholino knockdowns, ablations, and transplants, we hope to better understand how local cells can coordinate cellular pattern over a large field of cells.

Selected Publications

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Contact Info

Mustafa Kezar Khokha, MD
Patient Care Locations
Yale Pediatric Critical Care MedicineYale-New Haven Children's Hospital
1 Park Street, Ste West Pavilion 2nd Floor

New Haven, CT 06504
Yale Pediatric GeneticsYale-New Haven Children's Hospital
1 Park Street, Ste West Pavilion, 2nd floor

New Haven, CT 06504
Lab Location
Khokha LabFitkin Memorial Pavilion
789 Howard Avenue, Ste FMP 425

New Haven, CT 06519
Office Locations
PICU OfficeHunter Building
15 York Street, Ste 305

New Haven, CT 06510
Office - Mustafa KhokhaFitkin Memorial Pavilion
789 Howard Avenue, Ste FMP 410

New Haven, CT 06519
Mailing Address
Yale PediatricsPO Box 208064
New Haven, CT 06520-8064

Curriculum Vitae

Khokha Lab