The Spinner Lab focuses on the identification and understanding of genes that cause pediatric developmental disease. Lab director Nancy Spinner, PhD, has worked to merge her efforts as a clinical laboratory director involved in the diagnosis of cytogenetic, cytogenomic and genomic disorders, with research into the underlying mechanisms of genetic disease.
The lab has studied the autosomal dominant, multi-system disorder Alagille Syndrome since the early 1990s, identifying both Jagged1 and NOTCH2 as disease genes. Once these disease-causing genes were identified, the team was able to expand the phenotype of this variably expressed disorder, analyze the effect of missense mutations on gene function, and investigate factors that modify the expressivity, notably identifying Thrombospondin 2 as a modifier of liver disease severity in Alagille patients with a JAG1 mutation.
The Spinner Lab has also focused on understanding the potential genetic contribution to the less understood disorder, biliary atresia. The team has looked for genetic susceptibility factors via genome-wide association studies and identified several candidate genes and genomic regions. They have hypothesized that there is a genetic susceptibility that requires an environmental insult to cause the disease and taken several approaches to identify the putative genetic susceptibility factors. The lab has also worked to expand their understanding of several chromosome abnormalities, including chromosomal mosaicism in general as well as ring chromosomes 14 and 20, two rare chromosome abnormalities associated with seizure disorders. The current focus of the Spinner Lab is on the continued improvement of genomic diagnostics to better understand unsolved pediatric disorders, and how this information improves the lives of affected individuals.
Chief, Division of Genomic Diagnostics
Dr. Spinner's research focuses on the etiology and expressivity of pediatric developmental disorders. She uses genomic methods to focus on the multisystem disorder Alagille syndrome and biliary atresia, a likely heterogeneous and poorly understood condition. She is also interested in using genomic tools to continue to improve diagnostic rates for constitutional genetic disorders.