New generation of leaders in cancer research honored

November 13, 2001

NEW YORK, November 12, 2001 - Recipients of the first Paul Marks Prize for Cancer Research, a unique $125,000 award to be shared by young investigators for major accomplishments in cancer research, have been named. The prize, named after Paul A. Marks, M.D., President Emeritus of Memorial Sloan-Kettering Cancer Center (MSKCC), recognizes significant contributions to the basic understanding and treatment of cancer. This is the first major prize for most of the winners, who are no more than 45 years old. They were selected from among 49 nominees by a committee chaired by Joan Massagué, Ph.D., who leads MSKCC's Cell Biology Program.

"These investigators are still young, but they already are leaders in the field of cancer research," Dr. Massagué said. "Each of the four winners has made important contributions toward our understanding of cell division, cell death, and malignant transformation. The committee is very excited about honoring their work because they represent a new generation of leaders in cancer research."

Titia de Lange, a professor at Rockefeller University who just turned 46, is being honored for her discoveries of proteins that bind telomeres, the sections of DNA at the ends of chromosomes. She has described the key components of the protein machinery that maintains the lengths of these chromosomal ends. Loss of these specialized ends can cause chromosomes to stick together in ways that may contribute to cancer.

"Normal cells eventually stop dividing because they lose telomere function and we believe this is part of a tumor -suppressor pathway," said Dr. de Lange. "Tumor cells have found a way to circumvent this problem by maintaining their telomeres with every cell division. Our next step is to look at how normal cells are alerted when telomeres stop functioning, because this will tell us how the telomere tumor-suppressor pathway works."

Stephen J. Elledge, a professor with the Howard Hughes Medical Institute at the Baylor College of Medicine, identified two related but independent systems that have important roles in the cell cycle. One system helps cells sense and respond to DNA damage. This is important because when DNA is damaged, the cell must stop dividing so that the error can be repaired and not be passed on. Cells unable to sense damage are genetically unstable and cancer prone. "My hope is that once we fully understand this damage-recognition pathway, we'll be able to exploit the vulnerability of cells that don't have it and develop drug therapies to target those cells," Dr. Elledge said.

Dr. Elledge, who is 45, also discovered major components of a protein complex that targets other proteins in the cell for degradation. A failure to degrade proteins normally may underlie several diseases, including cancer.

William G. Kaelin, Jr., a 43-year-old investigator with the Howard Hughes Medical Institute at the Dana-Farber Cancer Institute, discovered the novel mechanism used by a normal protein, called VHL, to protect against tumors. The VHL protein is abnormal in von Hippel-Lindau disease, which is characterized by a high risk of certain types of cancer, especially kidney cancer. "This is a rare syndrome but it can teach us a lot about normal human physiology," Dr. Kaelin said. "As a clinician, I appreciate and understand the unusual features of this disease and I use those features to guide our research."

The risk arises because VHL normally causes the degradation of another protein, HIF, which stimulates the growth of blood vessels. When VHL is mutated, HIF is not degraded and tumor growth is enhanced by new blood vessels. Dr. Kaelin also has done important work on other proteins that control the cycle of cell division.

Work by the youngest investigator, Xiaodong Wang, a 38-year-old professor with the Howard Hughes Medical Institute, was conducted at the University of Texas Southwestern Medical Center. He unveiled a key, previously unsuspected biochemical step in the process of programmed cell death in mammalian cells. A failure to initiate cell death is now recognized as an important cause of some cancers. Dr. Wang showed that mitochondria play a surprising role in the death process by releasing several mitochondrial proteins including cytochrome C, an essential part of the cell's energy-making machinery.

"We now have a pretty good idea of what signals are involved in programmed cell death," Dr. Wang said. "What we don't yet know is how these signals are linked to the mitochondria. That connection is an important one in deciding whether cells live or die, and once we figure it out, it could be a target of future therapies."

"The beauty of the science conducted by each of these individuals is remarkable," said Harold Varmus, MSKCC President. "To accomplish this at a relatively young age deserves recognition, and this is the intent of the Marks Prize - to encourage investigators who have a unique opportunity to help shape the future of cancer research and treatment."
The winners will be honored with a dinner on December 18, 2001, and will speak about their work at a public symposium at MSKCC's Rockefeller Research Laboratories building on December 19, 2001. They will share a cash award of $125,000.

Dr. de Lange is the Leon Hess Professor and head of the Laboratory of Cell Biology and Genetics at The Rockefeller University, New York, New York. She received her Ph.D. degree in biochemistry from the University of Amsterdam and The Netherlands Cancer Institute.

Dr. Elledge is an HHMI investigator and Professor in the Department of Biochemistry at Baylor College of Medicine in Houston, Texas. He received his Ph.D. degree in biology from Massachusetts Institute of Technology.

Dr. Kaelin is an Associate Professor of Medicine at Harvard Medical School, an Associate Physician at Brigham and Women's Hospital, and an Attending Physician at Dana-Farber Cancer Institute, in Boston, Massachusetts. He received his M.D. degree from Duke University School of Medicine. He is also an HHMI investigator.

Dr. Wang is George L. MacGregor Distinguished Chair Professor in Biomedical Science at University of Texas Southwestern Medical Center in Dallas, Texas, and an Assistant Investigator in the Howard Hughes Medical Institute. He received his Ph.D. degree in biochemistry from UT Southwest.

In addition to Drs. Massagué and Varmus, the other members of the prize committee were Drs. Richard Axel of Columbia University; Stephen Burakoff of New York Medical College; Jeffrey M. Friedman of The Rockefeller University; Carol Prives also of Columbia; and Richard Rifkind, James Rothman, and David Scheinberg of MSKCC.

Memorial Sloan-Kettering Cancer Center is the world's oldest and largest private institution devoted to prevention, patient care, research, and education in cancer. Our scientists and clinicians generate innovative approaches to better understand, diagnose and treat cancer. Our specialists are leaders in biomedical research and in translating the latest research to advance the standard of cancer care worldwide.

Memorial Sloan Kettering Cancer Center

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