Mustafa Khokha, MD
Research & Publications
Biography
News
Locations
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 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.
Coauthors
Research Interests
Embryo, Nonmammalian; Germ Layers; Notochord; Organizers, Embryonic; Neural Plate
Research Images
Selected Publications
- Membrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTORSempou E, Kostiuk V, Zhu J, Cecilia Guerra M, Tyan L, Hwang W, Camacho-Aguilar E, Caplan M, Zenisek D, Warmflash A, Owens N, Khokha M. Membrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTOR. Nature Communications 2022, 13: 6681. PMID: 36335122, PMCID: PMC9637099, DOI: 10.1038/s41467-022-34363-w.
- Kap-β2/Transportin mediates β-catenin nuclear transport in Wnt signalingHwang WY, Kostiuk V, González DP, Lusk CP, Khokha M. Kap-β2/Transportin mediates β-catenin nuclear transport in Wnt signaling. ELife 2022, 11: e70495. PMID: 36300792, PMCID: PMC9665845, DOI: 10.7554/elife.70495.
- Mechanical stretch scales centriole number to apical area via Piezo1 in multiciliated cellsKulkarni S, Marquez J, Date P, Ventrella R, Mitchell B, Khokha M. Mechanical stretch scales centriole number to apical area via Piezo1 in multiciliated cells. ELife 2021, 10: e66076. PMID: 34184636, PMCID: PMC8270640, DOI: 10.7554/elife.66076.
- WDR5 Stabilizes Actin Architecture to Promote Multiciliated Cell FormationKulkarni SS, Griffin JN, Date PP, Liem KF, Khokha MK. WDR5 Stabilizes Actin Architecture to Promote Multiciliated Cell Formation. Developmental Cell 2018, 46: 595-610.e3. PMID: 30205038, PMCID: PMC6177229, DOI: 10.1016/j.devcel.2018.08.009.
- RAPGEF5 Regulates Nuclear Translocation of β-CateninGriffin JN, del Viso F, Duncan AR, Robson A, Hwang W, Kulkarni S, Liu KJ, Khokha MK. RAPGEF5 Regulates Nuclear Translocation of β-Catenin. Developmental Cell 2017, 44: 248-260.e4. PMID: 29290587, PMCID: PMC5818985, DOI: 10.1016/j.devcel.2017.12.001.
- Congenital Heart Disease Genetics Uncovers Context-Dependent Organization and Function of Nucleoporins at Ciliadel Viso F, Huang F, Myers J, Chalfant M, Zhang Y, Reza N, Bewersdorf J, Lusk CP, Khokha MK. Congenital Heart Disease Genetics Uncovers Context-Dependent Organization and Function of Nucleoporins at Cilia. Developmental Cell 2016, 38: 478-492. PMID: 27593162, PMCID: PMC5021619, DOI: 10.1016/j.devcel.2016.08.002.
- The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and lateralityBoskovski 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: 456-459. PMID: 24226769, PMCID: PMC3869867, DOI: 10.1038/nature12723.
- CFAP45, a heterotaxy and congenital heart disease gene, affects cilia stabilityDeniz E, Pasha M, Guerra M, Viviano S, Ji W, Konstantino M, Jeffries L, Lakhani S, Medne L, Skraban C, Krantz I, Khokha M. CFAP45, a heterotaxy and congenital heart disease gene, affects cilia stability. Developmental Biology 2023, 499: 75-88. PMID: 37172641, PMCID: PMC10373286, DOI: 10.1016/j.ydbio.2023.04.006.
- Mink1 regulates spemann organizer cell fate in the xenopus gastrula via Hmga2Colleluori V, Khokha M. Mink1 regulates spemann organizer cell fate in the xenopus gastrula via Hmga2. Developmental Biology 2022, 495: 42-53. PMID: 36572140, PMCID: PMC10116378, DOI: 10.1016/j.ydbio.2022.11.010.
- Discovering the Function of Congenital Heart Disease GenesGonzález D, Khokha M. Discovering the Function of Congenital Heart Disease Genes. 2022, 233-244. DOI: 10.1201/9781003050230-19.
- Disrupted ER membrane protein complex-mediated topogenesis drives congenital neural crest defectsMarquez J, Criscione J, Charney RM, Prasad MS, Hwang WY, Mis EK, García-Castro MI, Khokha MK. Disrupted ER membrane protein complex-mediated topogenesis drives congenital neural crest defects. Journal Of Clinical Investigation 2020, 130: 813-826. PMID: 31904590, PMCID: PMC6994125, DOI: 10.1172/jci129308.
- White paper on the study of birth defectsKhokha MK, Mitchell LE, Wallingford JB. White paper on the study of birth defects. Birth Defects Research 2017, 109: 180-185. PMID: 28398650, DOI: 10.1002/bdra.23590.
- Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in DevelopmentOwens NDL, Blitz IL, Lane MA, Patrushev I, Overton JD, Gilchrist MJ, Cho KWY, Khokha MK. Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development. Cell Reports 2016, 14: 632-647. PMID: 26774488, PMCID: PMC4731879, DOI: 10.1016/j.celrep.2015.12.050.
Clinical Trials
| Conditions | Study Title |
|---|---|
| Children's Health; Genetics - Pediatric | Pediatric Genomics Discovery Program (PGDP) |