Investigating Craniofacial Development and Dysmorphology

The Cox lab investigates the genetic contributions, and their interplay with environmental (nutritional and teratogenic) factors, to the presentation of cleft lip and palate , midface hypoplasia and other common craniofacial disorders.

Investigating the causes of cleft lip and palate

Chick embryo, prior to upper lip formation, in which a cleft lip gene (green) is electroporated into the facial epithelia

Chick embryo, prior to upper lip formation, in which a cleft lip gene (green) is electroporated into the facial epithelia.

Cleft lip, with or without cleft palate (CLP), is one of the most common birth defects, affecting around one in 700 children. The condition occurs when a child's lip, and often also the palate (the roof of the mouth), fail to come together during prenatal development.

Dr. Timothy Cox 's lab is studying how the proteins encoded by different CLP genes disrupt normal development of the face, and how environmental and/or dietary factors - including alcohol use and nutritional deficiencies - influence susceptibility to CLP. The team's ultimate goal is to unravel these connections and lay the foundation for measures that could prevent or minimize future cases of the disorder.

State-of-the art genetic and imaging tools

Polarized epithelial cells showing the localization of ZO1 protein (red) at the sites of adhesion. Nuclear DNA is blue.

Polarized epithelial cells showing the localization of ZO1 protein (red) at the sites of adhesion. Nuclear DNA is blue.

The lab's current research uses avian and murine model systems and has two distinct but integrated areas of investigation - one being a traditional wet lab with a strong molecular, cellular and developmental biology focus, while the second centers around quantitative 3-D imaging to understand the impact of individual gene mutations and non-genetic factors on development of the midface.

3D rendered image of a mouse embryo imaged using optical projection tomography showing the craniofacial cartilage (gold) and major vasculature (red)

3D rendered image of a mouse embryo imaged using optical projection tomography showing the craniofacial cartilage (gold) and major vasculature (red).

The wet lab's research focuses on understanding the role of a number of genes, including IRF6, the Nectins and the MID1/2 proteins, that cause CLP when mutated in humans. The lab uses traditional epithelial cell culture systems as well as procedures developed in-house for modulating gene expression in the early facial epithelia to understand the mechanisms controlling lip and primary palate formation.

The lab's imaging side investigates how dietary factors and individual genes influence early development of the face and proper formation of the craniofacial skeleton.

The lab is uniquely positioned in the craniofacial field because of its cell biological focus and research approaches to understand cleft lip pathology and its expertise in quantitative 3-D imaging. With respect to the latter, the lab has unique access to complementary high-resolution X-ray and light-based tomographic scanners. For more information about the scanners and our imaging work, visit the Small Animal Tomographic Analysis (SANTA) Facility .

Investigator Biography

Dr. Cox  

Timothy C. Cox, PhD, is a professor in the department of pediatrics at the University of Washington School of Medicine, and inaugural holder of the Laurel Endowed Chair in Pediatric Craniofacial Research. Cox is a member of Seattle Children's Research Institute's Center for Developmental Biology and Regenerative Medicine and an affiliate member of the University of Washington's Center on Human Development and Disability . He also holds an adjunct faculty appointment in both the University of Washington's Department of Oral Health Sciences and the Department of Anatomy and Developmental Biology at Monash University (Australia). 

Prior to joining Seattle Children's Research Institute, he held several leading positions in craniofacial medicine in Australia, including director of genetic programs at the Australian Craniofacial Unit and co-director of Monash University's MouseWorks, a highly regarded mouse genetic modification facility. Cox is also a past president of the Australia and New Zealand Society for Cell and Developmental Biology.