WASHINGTON (Dec. 21, 2018) — Craniofacial abnormalities are among the most prevalent birth defects, and are often caused by gene mutations. Branchiootorenal spectrum disorders (BOS) are included in that class of defects, causing hearing loss and kidney defects because of genetic mutations. Researchers at the George Washington University (GW) received a $1.9 million grant from the National Institutes of Health to study the known and unknown genes associated with BOS.
Principal investigators (PIs) on the grant include Sally A. Moody, PhD, chair of the Department of Anatomy and Cell Biology at the GW School of Medicine and Health Sciences; Karen Neilson, PhD, assistant research professor of anatomy and cell biology at the GW School of Medicine and Health Sciences; Dominique Alfandari, PhD, professor of developmental biology at the University of Massachusetts Amherst; and Francesca Pignoni, PhD, associate professor of ophthalmology, and interim chair of neuroscience and physiology at SUNY Upstate Medical University.
“Our research will focus on mutations in two genes linked to BOS: SIX1 and EYA1,” said Moody. “However, the causative genes for over half of BOS patients have yet to be identified. We hypothesize that there are other key co-factor proteins that bind to SIX1 to regulate its activity, and that mutations in these co-factors contribute to the unknown causes. We hope to identify these additional genes, which could lead to more comprehensive screening for infants with suspected hearing impairment.”
Using data published for Drosophila, the fruit fly, Moody and her co-PIs identified 15 vertebrate proteins that potentially bind to the SIX1 protein, many of them involved in expression in the developing ears and kidney, which could be potentially relevant to BOS. The team will use gain- and loss-of function approaches to determine whether any of these candidates play a role in inner ear or kidney gene expression and formation. They will also determine the impact, if any, on SIX1 function.
“Twenty years ago, before genomes were sequenced, when we were doing all sorts of library screening and old-fashioned molecular biology and sequencing, we were looking for genes involved in early neural development,” said Moody. “We came across the SIX1 gene and it had a unique expression pattern in the sensory organs of the head. My lab has spent the last 20 years trying to figure out what it does. We look forward to this next step in our research.”
The project, titled “SIX1 Co-factors in Craniofacial Development,” began in August 2018 and will continue through May 2023.
For more information on Moody’s research, visit the Moody Lab.
