Department of Biology Center for Regenerative Biology and Medicine
Craniofacial and skeletal deficits associated with Down syndrome
Individuals with Down syndrome (DS) display phenotypes including cognitive, cardiac, craniofacial and skeletal abnormalities. Our laboratory has investigated craniofacial and skeletal phenotypes in DS using mouse models as well as clinical data from infants with DS in collaboration with Riley Hospital for Children. Our collaborative preliminary data from infants with DS suggests that over half of 0-6 month infants with DS had some degree of dysfunction related to craniofacial structure that warranted further investigation to ensure proper growth of these infants. The long term goal of our translational research is to understand the molecular and genetic bases of craniofacial and skeletal defects in DS and develop effective screening, therapeutic and preventative strategies. Our central hypothesis is that Trisomy 21 disrupts fundamental genetic and cellular mechanisms in development that cause craniofacial and skeletal abnormalities and adversely affect individuals with DS. We seek to overcome these disruptions by etiological based treatments and clinical practices. To this end, our laboratory has shown that trisomy disrupts essential genetic and cellular pathways, including those involving Dyrk1a and Nfat as well as the neural crest, important in early craniofacial and skeletal formation. Our preliminary and other published evidence suggest that therapeutic treatment with substances that inhibit Dyrk1a activity may correct mandibular precursor, growth retardation, and skeletal deficits associated with DS. Our quantification of craniofacial and skeletal properties in DS mouse models during development after treatment will determine potential clinical applications for individuals with DS. Testing etiological based therapies in mouse models is an essential next step to improving the quality of life for individuals with DS by improving deficits in craniofacial formation and by extension, functional abnormalities.