{"id":1279,"date":"2016-09-16T11:04:59","date_gmt":"2016-09-16T18:04:59","guid":{"rendered":"https:\/\/keck.usc.edu\/news\/usc-researchers-awarded-3-3-million-nidcr-grant-to-find-more-effective-treatment-for-common-birth-defect\/"},"modified":"2023-11-19T12:15:28","modified_gmt":"2023-11-19T20:15:28","slug":"usc-researchers-awarded-3-3-million-nidcr-grant-to-find-more-effective-treatment-for-common-birth-defect","status":"publish","type":"post","link":"https:\/\/keck.usc.edu\/news\/usc-researchers-awarded-3-3-million-nidcr-grant-to-find-more-effective-treatment-for-common-birth-defect\/","title":{"rendered":"USC researchers awarded $3.3 million NIDCR grant to find more effective treatment for common birth defect"},"content":{"rendered":"\n \n \n\n\n\n\n\n\n\n
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\n\n \n Press Release<\/span>\n\n\n\n<\/div>\n \n \n
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USC researchers awarded $3.3 million NIDCR grant to find more effective treatment for common birth defect<\/h1>\n\n\n<\/div>\n \n \n
\n John Hobbs<\/span>\n \n September 16, 2016<\/span>\n <\/div>\n \n \n
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Human skull with sutures (Public domain image courtesy of Gray's Anatomy)<\/figcaption>\n <\/figure>\n \n \n \n\n<\/div>\n \n\n <\/div><\/div>\n\r\n\r\n\n\n \n \n\n\n\n\n\n\n\n
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It might surprise you to learn that your cranium is not one continuous smooth bone encasing your brain.
\nIt\u2019s actually comprised of eight bones, separated by fibrous joints, to give your skull flexibility. That\u2019s the reason babies have \u201csoft spots\u201d and your brain was able to continue growing unabated throughout childhood.
\nWith craniosynostosis\u2014a birth defect estimated to occur in roughly one out of every 2,500 live births\u2014the fibrous joints (or sutures) fuse together prematurely, leaving the cranium little room to expand to accommodate the growing brain. In a mild case, this may lead to a misshapen skull. In more severe cases, it can cause developmental delays, hearing loss, blindness and even death.
\nBut maybe not for long, thanks to a $3.3 million grant from the National Institute of Dental and Craniofacial Research (NIDCR), which could eventually lead to more effective treatments.
\n<\/span>\u201cThis is not just awesome funding,\u201d said Yang Chai, associate dean of Research at the Herman Ostrow School of Dentistry of USC and one of three principal investigators on the study. \u201cIt also showcases what great collaborations can do, bringing three principal investigators together at this university so we can work on a complex problem like craniosynostosis.\u201d
\nJoining Chai are Rob Maxson, professor of biochemistry and molecular biology, and Gage Crump, associate professor of stem cell biology and regenerative medicine, both from the Keck School of Medicine of USC.
\nWith the five-year project, titled \u201cMolecular and Cellular Basis of Craniosynostosis,\u201d the three researchers will leverage their complementary expertise in craniosynostosis, stem cells, genetics and craniofacial bone development to better understand the genetic and molecular mechanisms behind suture development.<\/p>\n

Stem Cells, Not Scalpels<\/h3>\n

At the center of the study are two genes called\u00a0TWIST1<\/em>\u00a0and\u00a0TCF12<\/em>, mutations of which have been discovered to contribute to craniosynostosis.
\n\u201cThose genes really give us an entr\u00e9e into the molecular and developmental processes that are going awry in craniosynostosis,\u201d said Maxson, who helped to identify\u00a0TWIST1<\/em>\u00a0and\u00a0TCF12<\/em>\u2019s role in suture development.
\nNot only will the scientists delete the two implicated genes during various stages of development using a mouse model, they will also observe the cranial suture fusion in zebrafish. Both animals develop craniosynostosis just like humans.
\n\u201cThe great thing about zebrafish is that they\u2019re laid as one-cell embryos, they develop completely outside the mother, and they\u2019re largely transparent,\u201d said Crump, a zebrafish geneticist. \u201cWe can do live imaging on the fish to look at the bones as they\u2019re developing and see what\u2019s going wrong when the sutures fuse.\u201d
\nBy better understanding the genetic and molecular processes underpinning craniosynostosis, the researchers hope to one day develop biological interventions to treat craniosynostosis, rather than traditional surgical treatments, which often have to be done multiple times and have a high morbidity rate.
\n\u201cIt\u2019s a very traumatic surgery,\u201d Crump explained. \u201cThey take the whole skull cap off the child, fragment the bones and transplant the bones back into the skull.\u201d
\nCrump said their research could eventually lead to a pharmacological intervention that compensates for the loss of the\u00a0TWIST1<\/em>\u00a0and\u00a0TCF12<\/em>\u00a0genes, which would keep the sutures open for normal brain development and make numerous surgeries unnecessary.<\/p>\n

Greater than the Sum of the Parts<\/h3>\n

Each of the researchers brings decades of expertise to the study.
\nChai is widely recognized throughout the dental and craniofacial research community for his investigations of the molecular and cellular mechanisms of craniofacial development, including oral and facial birth defects such as cleft palate. He is the director of USC\u2019s Center for Craniofacial Molecular Biology.
\nIn a\u00a0Nature Cell Biology<\/em>\u00a0article published last year, Chai identified a population of stem cells that are required for long-term suture patency and calvarial bone growth.
\nCrump has pioneered live imaging techniques in zebrafish to examine the cellular basis of craniofacial defects. He is the principal investigator of the\u00a0Crump Lab<\/a>, which researches how genes affect bone and cartilage development in zebrafish.
\nMaxson has long-standing expertise in mouse models of synostosis, having contributed to the identification of\u00a0TWIST1<\/em>\u00a0and\u00a0TCF12\u00a0<\/em>as the two most affected genes in Saethre-Chotzen syndrome, a rare congenital disorder characterized by craniosynostosis. His lab also described the first mutation in people,\u00a0MSX2<\/em>, that causes craniosynostosis, in the 1990s.
\nMaxson and Chai have been collaborating on research for more than 20 years and together recruited Crump to USC.
\n\u201cThis study involves faculty members from two different schools, but we have a long history of very productive collaboration and a mutual trust that makes this venture possible,\u201d Chai said.
\n\u201cI think each one of us individually could have done something that would\u2019ve been useful and interesting, but I think when you put the three of us together, there really is a synergism,\u201d Maxson said. \u201cI think there\u2019s a good chance that we\u2019ll do what this grant is intended to do and that is to come up with something where the whole is greater than the sum of the parts.\u201d
\nResearch reported in this publication was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under Award Number R01DE026339.<\/p>\n\n\n\n<\/div>\n <\/div>\n\n\n <\/div><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":118,"featured_media":1280,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"advgb_blocks_editor_width":"","advgb_blocks_columns_visual_guide":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[6],"tags":[436],"class_list":["post-1279","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-press-release","tag-usc-stem-cell"],"acf":[],"yoast_head":"\nUSC researchers awarded $3.3 million NIDCR grant to find more effective treatment for common birth defect<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, 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