Calcium might be a key to understand Wolfram syndrome

We have recently found a critical enzyme executing cell death in Wolfram syndrome. It seems like that activity of this enzyme is regulated by calcium. Based on our preliminary data, endoplasmic dysfunction creates a shunt between the endoplasmic reticulum and the cytosol, leading to calcium leakage into the cytosol. This may be a key event that can cause cell death. We are actively looking for drugs that can prevent this event.

www.erstress.com, updated our lab web site

I have updated our lab web site. I will start hiring new staff members and taking fellows here at Washington University to accelerate our progress.

My funding for Wolfram syndrome research in 2012

I have been working very hard to obtain funds supporting research and clinic for Wolfram syndrome. Here is the list of my research funds related to Wolfram syndrome in 2012.

1. 112-CT-61 (Urano, Hershey, Marshall) 1/1/12-12/31/14
American Diabetes Association
Identifying Biomarkers for an Endoplasmic Reticulum (ER) Stress Related Diabetes
     This study proposes a novel strategy that will assess patients with Wolfram syndrome (WS), a disease caused by a single mechanism that causes stress in the cells endoplasmic reticulum (ER).

2. ICTS (Urano, Hershey, Marshall)                  6/1/11-5/30/13
Support for clinic                            
Translating mechanisms for a genetic neurodegenerative diseases into new therapies

3. R01DK067493 (Urano)                          9/30/10-6/30/14
National Institutes of Health           
Endoplasmic Reticulum Stress and Diabetes
     This study proposes to study the mechanisms of ER stress-mediated cell death in Wolfram syndrome and type 1 and type 2 diabetes.

4. 40-2011-14 (Urano)                            10/01/10-9/30/12
Juvenile Diabetes Research Foundation
Targeting ER Enzymes for Enhancing Human Beta Cell Mass And Function
     This study proposes to develop a method for increasing Wolfram syndrome 1 gene function for enhancing human beta cell mass and function in patients with juvenile-onset diabetes.

5. 47-2012-760 (Urano)                            9/01/12-8/31/13
Juvenile Diabetes Research Foundation      
Identifying beta cell ER stress biomarkers for predicting type 1 diabetes
     This study proposes to identify beta cell ER stress biomarkers for predicting juvenile-onset diabetes including Wolfram syndrome using bioinformatics.

Two new ways of getting disease treatments to patients faster

Dr. Francis Collins, current Director of National Institues of Health, beautifully articulated two new ways of getting disease treatments to patients faster: repurposing existing drugs, and testing on fabricated human tissue. I agree with him and am currently using the same strategies that he mentioned in this video.

http://www.youtube.com/watch?v=spUoPC_TU_8

Discovery of a mechanism inducing cell death by ER dysfunction

We have discovered a critical mechanism inducing cell death by endoplasmic reticulum dysfunction. This mechanism is activated in a mouse model of Wolfram. We need to verify this mechanism is also activated in patients with Wolfram.

If we can prevent the activation of this cell death mechanism, we may be able to delay the progression of the disease. This will be published in a top journal. So Cell press, Washington University, JDRF (juvenile diabetes research foundation) and other communications media are coordinating a press release. This would be a great opportunity for us to raise awareness of Wolfram.