I moved to Washington University Medical Center in July, 2012. My focus has been to develop novel treatments for Wolfram syndrome. I believe in the strong power of rare diseases, especially Wolfram syndrome, to understand the pathogenesis and develop novel therapeutic modalities for more prevalent forms of diabetes, type 1 diabetes and type 2 diabetes.
It has been shown that genetic variations of WFS1, a causative gene for Wolfram, are associated with type 2 diabetes. My hypothesis is that a certain variation of WFS1 gene makes our pancreatic beta cells more susceptible to environmental stress, more specifically endoplasmic reticulum (ER) stress. Drugs that can alleviate ER stress should be beneficial for this group of patients with type 2 diabetes.
In type 1 diabetes, ER dysfunction may produce abnormal structure of insulin in pancreatic beta cells, leading to autoimmune-mediated destruction of beta cell and diabetes. We have scientific evidence supporting this model, and are trying to publish the data. For this group of patients with type 1 diabetes, drugs that can restore ER dysfunction should be beneficial.
Its monogenic aetiology makes Wolfram syndrome more amenable to dissecting out the mechanisms underpinning cellular responses to ER dysfunction than other diabetic conditions, type 1 and type 2 diabetes, in which multiple factors typically interact to produce the disease manifestations. Thus, Wolfram syndrome represents an ideal model to identify novel biomarkers and drugs for type 1 and type 2 diabetes. I believe that “A cure for Wolfram syndrome could lead to a cure for diabetes.”