Four new grants

We received 16 applications this year from all over the world, from as far away as Switzerland, the Netherlands and Canada. Ten of these grants were outstanding. This is a huge improvement over last year.

Each grant will have a significant impact on VHL science and our understanding of the disease process. Major breakthroughs have occurred in the last few years, leading us to explore new questions that will result in new therapies in the not too distant future.

The Board voted in June to award four grants, for a total of $120,000 in new grants this year. Because we are still paying second-year funding to Dr. Judith Frydman of Stanford, we will pay out a total of $160,000 in grant money between now and June 2006.

We are encouraging young researchers to study VHL, and helping them gather data so that they can solve another piece of the puzzle of VHL in particular and cancer in general. You will notice that this year much of the work focuses on kidney cancer. Drugs are somewhat easier to test in the kidney than in other organs, but the mechanism is the same and hopefully the same drugs will work throughout the body.

Researchers you are supporting 2005-2006

Dr. Judith Frydman of Stanford has completed her first year of the 2-year grant we awarded last year. With the support of the VHL Family Alliance she has published a paper in the prestigious journal Cell, which raised a great deal of interest in the scientific community and was reviewed in three other journals. Her work helps us to understand the process of “folding” which is important to the correct functioning of the VHL protein. When the protein cannot fold properly, the body invokes a kind of quality control process intended to dispose of the incorrectly folded protein, making way for correctly folded protein instead. This paper describes the different sets of “chaperone” proteins needed for correct folding, and for elimination of incorrectly folded protein.

Dr. Ian Frew, of the department of cell biology at the Swiss Federal Institute of Technology, is working toward better therapies for kidney cancer, by improving our understanding of how the VHL protein works, and specifically what other events are needed for the tumor to progress to cancer. He will study closely the interaction among the loss of VHL, a change in PTEN, and a disruption of the P13K pathway. If interactions among these are proven, this would be a very attractive target for drug development to aid in the control of kidney cancer.

Dr. Kimryn Rathmell (an oncologist) and Dr. Shufen Chen (a renal pathologist) at the University of North Carolina at Chapel Hill have been investigating the activities of the VHL protein which normally acts to prevent the development of kidney cancer. They are making a series of animal models (mice), each with small changes in the VHL gene, that will allow us to learn important things about the biology of VHL-induced kidney cancer, and will aid in testing proposed new therapies.

Pei-Yin Lin is a doctoral candidate in the Graduate Group of Immunology at the University of California, Davis, working with Dr. Robert Weiss (nephrology). Kidney cancer does not respond well to most kinds of chemotherapy. One possible reason is that protein p21, which works against chemotherapy, is elevated in kidney cancer. Lin will be studying p21 and using a method of neutralizing some of the effects of p21, to see if the kidney will respond better to chemical treatments.

Dr. Andreea Ruxandra-Schmitzer [left] is an Assistant Professor at the University of Montreal working on the chemical modification of proteins. In this project, she is working with Dr. Shawn Collins [right] on creating “molecular clips” to stabilize and deactivate telomerase, an enzyme found in most human tumors, that has been found to be a powerful marker and therapeutic target in cancer. By doing so, they hope to prevent the progress and spread of VHL tumors.

Thank you! -- Let's Do It Again!

As printed in the VHL Family Forum 13:3, Annual Report 2005. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.