William G. Kaelin Jr., MD

Dana-Farber Cancer Institute

Nominated by: VHL Family Alliance

My first introduction to Dr. Kaelin was when the phone rang one Sunday about 1994.  "Is this the VHL Family Alliance?"  "Yes."  "And you're in Brookline?" "Yes."  "I could practically throw a stone over there from my office!"  In his first venture on the Internet, he had typed "VHL" into a search engine, and found our little website.  We had a long talk about VHL.  He had done some very important work with retinoblastoma, and was interested in VHL, another tumor-suppressor gene.

Since then, Dr. Kaelin has made enormous strides in helping us understand the function of the VHL protein in the cell.  He and his team have written a large number of papers, and researchers who trained in his lab have gone on to found exciting labs of their own (for example, Dr. Othon Iliopoulos who now heads a medical genetics practice and research lab at Massachusetts General Hospital).

His overarching goal is to understand why mutations affecting tumor-suppressor genes cause cancer. He works to lay the foundation for the development of new anticancer therapies based on the biochemical functions of specific tumor-suppressor proteins.

One of his key discoveries, published in 2001 in the journal SCIENCE, was that hydroxylation is used as a signaling mechanism.  This was one of the major clues to understanding angiogenesis (formation of new blood vessels).  Dr. Kaelin discovered that when oxygen levels are normal, the VHL protein helps mark another cellular protein, called HIF, for destruction. When oxygen levels fall, HIF is allowed to persist, so it can restore a healthy supply of oxygen by promoting blood vessel growth and stimulating erythropoietin production.  This work has led to the development of drugs that regulate VEGF, two of which are already on the market.

He has published seminal papers on retinoblastoma, von Hippel-Lindau (VHL), tuberous sclerosis (TS), pheochromocytoma, and the field of angiogenesis inhibition in general.

Dr. Kaelin's work has been recognized by his election in 2007 to the Institute of Medicine of the National Science Foundation.  Membership in IOM is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service. Current active members elect new members from among candidates nominated for their accomplishments and contributions to the advancement of the medical sciences, health care and public health.

Those of us with VHL are particularly grateful for his kindness and his passion for finding answers that will translate into medicines and treatments in the clinic.  We value his partnership not only in VHL but in the many other cancers and related diseases touched by these basic cellular mechanisms.  We recommend him to you as an honoree in rare disease research.

Von Hippel-Lindau disease is caused by a tiny misspelling in one gene on one copy of chromosome 3.  This tiny flaw puts the person at increased risk of tumors of the retina, brain, spinal cord, kidney, pancreas, adrenal glands, and various other organs.  People with this disease experience a series of tumors throughout their lifetime.  The VHL gene is one of the primary regulatory mechanisms of the process of angiogenesis (blood vessel development), oxygen sensing, glucose processing, and more.

In the general population, changes to the VHL gene during one's lifetime may cause kidney cancer and many other sporadic tumors.  We now know that all clear cell renal cell carcinoma (85% of all kidney cancer tumors in the general population) contain changes to the VHL gene in the tumor.  Thus research on VHL has the potential to unlock the secrets of many cancers.