Dr. Rosemary Cater

Understanding the molecular role of WFS1 and how mutations in this protein cause Wolfram syndrome.

Wolfram syndrome manifests as a genetic disorder marked by early-onset diabetes, progressive optic atrophy, and hearing loss. In addition to these defining symptoms, some individuals may also experience neurological complications, including motor impairments, neurological disorders, and deficits in memory and learning. Tragically, Wolfram syndrome carries a high mortality rate, and currently, there are no therapeutic interventions available to halt or slow its progression. This lack of effective treatment stems, in part, from our incomplete understanding of the disease’s underlying mechanisms.

While it is known that Wolfram syndrome is caused by mutations in the WFS1 gene, the precise role of the WFS1 protein in healthy individuals remains elusive, as does the link between its various mutations and Wolfram Syndrome. Our research is focused on understanding the molecular function of the protein encoded by WFS1, and what this protein looks like on an atomic level. By gaining these molecular insights into the normal WFS1 protein, we will be able to understand how mutations in this protein disrupt its activity and cause Wolfram syndrome.

Through a collaborative effort with Prof Vania Broccoli (San Raffaele Hospital and CNR-Institute of Neuroscience in Milan) and Prof Filippo Mancia (Columbia University, USA), we have preliminary results that are already helping us understand what this protein looks like and are enthusiastic about furthering this research to fill this gap in knowledge within the field, and ultimately contribute to the development of effective treatments for Wolfram syndrome.