Research efforts you are supporting 2008-2009

Thera Links, M.D., Ph.D., of the University of Groningen in the Netherlands, has completed the preparations for the study she began for us last year.  She is now ready to begin scanning patients in her project “Visualizing VEGF producing lesions in von Hippel-Lindau.”  When the second copy of the VHL gene is inactivated in a cell there is heightened production of the vascular endothelial growth factor (VEGF).  The greater the production of VEGF, the higher the growth rate of the tumor. 

Dr. Links and colleagues have developed a radioactive labeled antibody, based on bevacizumab (Avastin) which binds to VEGF, making it possible to see concentrations of VEGF on a PET scan.  They will be scanning 30 people with VHL to detect and quantify the level of VEGF production in VHL-associated lesions.  The goal is to use the information learned through these scans to formulate a plan for monitoring and treatment of these patients.

Rachel Giles, M.D., Ph.D., of the University of Utrecht, also in the Netherlands, has developed a unique animal model for VHL, a zebrafish with no VHL gene at all.  An animal model allows scientists to watch tumors develop in the body of the animal, and test the reaction of the tumor to various treatments.  Small animals that go through many generations in a short period of time are preferred, allowing the researcher to see the consequences of a treatment quickly. 

Zebrafish are particularly interesting because they are small and transparent.  You can see right through them.  With the aid of a microscope and various contrast media, you can observe changes in the blood vessels while the animal continues to live.  Dr. Giles; team will be systematically testing VHL patient mutations by injecting this mutation into a zebrafish embryo and watching the development of the fish.  They can inject hundreds of zebrafish embryos in a single morning and perform the phenotypic analysis within two weeks.

In the four pictures shown here, the lower two pictures are of the eye of a fish with no VHL protein (vhl -/-).  The top two pictures are of the eye of a fish at the same age with normal VHL protein function (vhl +/+).  In the centers of the two left-hand pictures you can see that where the eye with normal pVHL has only three visible blood vessels, the eye with no pVHL has many blood vessels.  In the two right-hand pictures, you can see those same blood vessels from the top.  In full motion under the microscope, you can see the blood pulsing through these vessels, or watch cells divide.  As time goes on, more blood vessels grow, forming a hemangioblastoma.

Different drugs can be tested to see if the tumor responds.

VHLFA continues to invest in building a robust Research Infrastructure consisting of surgically removed tissue and donations of tissues after death.  These priceless biomaterials are the essential building blocks for all research.  Our bank continues to grow, with 357 samples collected from 24 donors, and nearly 60 people registered with the Tissue Bank.   We are working to double that number this year.

As printed in the VHL Family Forum 17:4, Annual Report 2009. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.