800-627-5482
swf@sturge-weber.org

The Sturge-Weber Foundation is happy to announce these new grants

Report from Charles Swindell, PhD, SWF Consultant

 

Request for grant applications for financial support of research related to Sturge-Weber syndrome was announced by the Foundation this past September 2013. We were delighted to receive a number of impressive applications.  

 

These applications were reviewed by The Medical Advisory Board:   Alex V. Levin, MD, MHSc, FRCSC, Wills Eye Institute; Chair, SWF Medical Advisory Board Mustafa Sahin, MD, PhD, Boston Children’s Hospital; Member, SWF Medical Advisory Board Michael H. Gold, MD, Medical Director, Gold Skin Care Center; Member, SWF Medical Advisory Board as well as two independent expert reviewers.  

 

Two applications— Jonathan Pevsner. PhD.  Associate Professor, Johns Hopkins University School of Medicine and Kennedy Krieger Institute and Kristen Kelly, M.D. Professor , University of California, Irvine – have been selected for funding.

 

We are delighted to be able to support the kind of high quality research programs that Jonathan and Kristen will undertake and are confident that the achievement of their objectives will hasten our progress toward better care and treatment options for those with SWS.  We look forward to hearing of their progress.   Brief summaries of Jonathan’s and Kristen’s research programs follow.

 

Jonathan Pevsner, PhD, Associate Professor, Johns Hopkins University School of Medicine and Kennedy Krieger Institute. 

“From discovering the Sturge-Weber mutation to basic research enabling treatment strategies.”

First year:  $29,796

Second year:  $25,604

Total:  $55,400  

We recently identified mutations in the GNAQ gene as the cause of Sturge-Weber syndrome (SWS). We did this in collaboration with Dr. Anne Comi (Director, Hunter Nelson Sturge-Weber Center at Kennedy Krieger Institute) and Dr. Douglas Marchuk (Duke University).

 

To do this we sequenced the genomes of affected and unaffected parts of the body of three individuals, then confirmed the finding by sequencing 97 samples from 50 individuals

 

GNAQ is a gene that specifies a protein, Gαq, that regulates pathways inside cells controlling basic functions such as growth of cells and their ability to respond to signals. Gq responds to a chemical messenger (called GTP) by binding it, thus activating pathways inside cells, and then breaking it down.

 

In SWS Gαq is persistently activated to a small but significant extent. If Gαq is like a switch with “on” and “off” positions, in SWS the switch is locked into the partially “on” position.

 

We propose experiments to further understand the basic biology of SWS and how to develop treatment strategies.

(1) We propose to set up a screen, made available to the entire SWS research community, to sequence DNA samples from patients. Because of the nature of the mutation—from about 82% to 99% of DNA in a SWS sample are normal, while just 1% to 18% harbor the mutation—specialized DNA sequencing is needed.

(2) We propose to create an antibody that is specific to the mutant form of Gαq. This will allow us to determine which cell type(s) harbor the Gαq mutation. This antibody will also be shared with the research community and is likely to greatly facilitate SWS research.

(3) We propose to characterize the biochemical changes that occur in the mutant Gαq. This includes studying its GTP binding properties, its protein interaction partners, and the receptor(s) it is coupled to. This information is essential to develop treatment strategies.

 

Kristen Kelly, MD, Professor, University of California, Irvine 

“Vascularized Port Wine Stain Skin Model for Evaluation of Cell Types in Lesion Pathogenesis.” 

First year:  $14,973

Second year:  $15,025

Total:  $29,998  

The cause of port wine stain birthmarks (PWS) is unknown and this makes development of good new treatments difficult. Our experiments will help us better understand what causes PWS in order to identify targets for treatment.

 

It is not known whether the problem is due to the cells that form blood vessels or to an abnormality in their environment. First, we will take biopsies from PWS and separate the three main cell types found in these lesions: the cells that form blood vessels, support cells, and the cells of the top-layer of skin.

 

We will construct a model of a PWS using these cells. In a series of experiments we will mix and match normal and PWS variants of the three main cell types to determine which cell type(s) contribute most to the disease. In addition, we will test the different cell types to determine which of them contains the gene change that was recently identified by researchers supported by the Sturge-Weber Foundation.

 

A better understanding of how blood vessels in PWS are growing abnormally and what cells are primarily responsible for this change is the next important step for research supported by the Sturge-Weber Foundation and together we can use knowledge to develop targeted treatments to eliminate the physical and psychosocial trauma associated with these lesions.