Nine VHL research proposals were submitted to the VHLFA this year. Because of your generosity we were able to fund five of these. Nonetheless there is a great deal more work to be done. Hospitals and universities are cutting back their own spending on research, so those of us who want VHL research to move forward swiftly need to fill this gap. Even with a modest budget, however, we have made a significant contribution to the advancement of VHL research.

One of the stated goals of our research grants program is to assist young researchers in gathering sufficient data to prove the validity of their ideas so that they can qualify for other larger grants elsewhere and continue their research. In this regard, we are very happy to announce that in 2001 Dr. Maria Czyzyk-Krzeska, whom we funded for two years (1999 – 2001), was able to obtain substantial funding from the NIH (National Institutes of Health) and the ACS (American Cancer Society) for the continuation of her research on the Role of VHL in Pheochromocytoma. Similarly, Dr. Ehud Gazit at Tel-Aviv University, whom we funded last year, has won a very large grant from the Israel Cancer Research Fund, to continue his work on ‘The Role of Protein Folding and Stability in the VHL Syndrome’.

There are two aspects we are focusing on in this year’s grants. First, we continue to learn more about how the VHL protein (pVHL) operates in the cell – what it regulates in normal function, and what doesn’t work when pVHL is not present. Second, we are trying to move from this knowledge to real therapies. This work moves ahead more quickly when there is a "biological model", preferably one that goes through many generations in a short period of time so that genetic changes can be tracked. The mouse and even the fruit fly have a VHL gene. This shows how very essential a role the VHL gene plays in the cell.

We have renewed funding for a second year for Dr. Robert J. Duronio of the University of North Carolina to further his research on E3 Ubiquitin Ligase Complexes’. pVHL’s role within the E3-ubiquitin ligase is often compared to that of a ‘g Page arbage collector’, functioning as an "off" switch by gathering up certain cellular proteins that are needed for cellular growth and proliferation. The investigators have made good progress on the goals they set out to accomplish over the past year of funding, and are continuing and extending that work.

Dr. Georges Mer of the Mayo Clinic in Minnesota is investigating how the VHL protein binds to another key protein named HIFa. These studies increase our knowledge of how pVHL and HIF1a interact, thus helping in search for drug molecules that can restore the normal function of pVHL.

Dr. Tien Hsu of the University of South Carolina is interested in addressing how pVHL mutations cause cancer growth and metastasis. Dr. Hsu has identified a pVHL-interacting protein named nm23 (nm: non-metastatic), which may be a good target for therapeutic intervention. Fortunately, nm23 belongs to a class of enzymes that have been very well studied, so drug development should be feasible.

Dr. Daniel George of the Dana Farber Cancer Research Institute in Boston proposes to use the Novartis Pharmaceuticals drug PTK/ZK to carry out a Phase II clinical trial to treat patients with VHL, especially those with advanced central nervous system disease. The VHL study is due to open to VHL patients in December 2002.

Thank you very much for giving me this grant. I assure you that the funding will be put to good use. My gratitude to the VHL Family Alliance for this great opportunity.

-- Georges Mer, Mayo Clinic

Pierre Jacomet and a team at the Catholic University Medical Center in Santiago, Chile, are studying "Pheochromocytoma and Altered Mental Function." The objective is to compile data on the number of people suffering from panic attacks and other personality disorders that could be traced to undetected pheochromocytomas. With the help of statistical information, he hopes to raise the visibility of this issue so that health care professionals will be more likely to suspect and diagnose a pheochromocytoma.

Dr. Gorospe is Investigator Chief of the Cell Cycle Control Unit, Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health

As printed in the VHL Family Forum 10:4, December 2002. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org.