Researchers share Nobel Prize for discoveries that may improve treatment of cancer, anemia

William G. Kaelin Jr., MD 
William G. Kaelin Jr.
Gregg Semenza 
Gregg L. Semenza

Three scientists — two from the United States and one from England — have been awarded the Nobel Prize in Physiology or Medicine for their discoveries of how cells sense and adapt to oxygen availability.

The recipients — William G. Kaelin Jr., MD; Sir Peter J. Ratcliffe, MD; and Gregg L. Semenza, MD, PhD — were announced by the Nobel Assembly at Karolinska Institute in Stockholm during a ceremony earlier today.

Research done in the labs of these three investigators provided insight into how different oxygen levels regulate the body’s physiological processes.

“The seminal discoveries by this year’s Nobel Laureates revealed the mechanism for one of life’s most essential adaptive processes,” the Nobel Committee said in a press release. “They established the basis for our understanding of how oxygen levels affect cellular metabolism and physiological function. Their discoveries have also paved the way for promising new strategies to fight anemia, cancer and many other diseases.”

Kaelin is Sidney Farber professor of medicine at Harvard Medical School, professor of medicine at Dana-Farber Cancer Institute, and senior physician in medicine at Brigham and Women's Hospital.

His contributions to this year’s Nobel Prize focused on identifying the cellular components of the hormone erythropoietin’s response to hypoxia. The work led to the discovery of the hypoxia-inducible factor (HIF), a protein complex that binds to an identified DNA segment in an oxygen-dependent manner.

“Science today is not done by individuals but by an ecosystem,” Kaelin said during a press conference earlier today at Dana-Farber. “There are countless examples where my work has been made better not only by the people at Dana-Farber but by the fabulous biomedical ecosystem we have here in Boston.”

Kaelin dedicated the prize to his late wife — Carolyn Kaelin, MD — who was a breast cancer surgeon at Dana-Farber.

“Like most scientists, I occasionally let myself dream that this may one day happen,” Kaelin said, adding that he and his wife used to laugh about the idea of him winning a Nobel Prize.

Semenza is professor of pediatrics, radiation oncology and molecular radiation sciences, biological chemistry, medicine and oncology at Johns Hopkins University School of Medicine. He also is director of the vascular program at the Institute for Cell Engineering.

Semenza’s research on how cells sense and adapt to oxygen availability centered on the levels of erythropoietin and its response to hypoxia. It showed that specific DNA segments near the gene regulated the response to hypoxia in gene-modified mice.

“This is an award that is shared by everybody at Johns Hopkins past and present, because I couldn’t have done it without my colleagues,” Semenza said during a press conference earlier today at Johns Hopkins. “I have been fortunate to have a long list of students and post-docs who have worked in my lab who have all contributed to this honor.”

Ratcliffe is the director for the Target Discovery Institute within the Nuffield Department of Medicine at Oxford University, as well as director of clinical research at Francis Crick Institute in London. His work examined oxygen-dependent regulation of the erythropoietin gene and showed that an oxygen-sensing mechanism was present in nearly all tissues.

“This discovery of how oxygen interacts with tissues is a powerful reminder of how the biggest discoveries come from the understanding of basic mechanisms,” George Q. Daley, MD, PhD, dean of Harvard Medical School said during today’s press conference.

“The discoveries made by [Kaelin] and his colleagues have fundamentally defined how cells respond to oxygen. ... Their work has broad application across a broad swath of medicine,” added Elizabeth Nabel, MD, president of Brigham Health.

Semenza was asked during the press conference what impact the science behind this year’s Nobel Prize in medicine will have for those suffering from disease — particularly those with cancer.

His response highlighted a deficiency in proper targeting among today’s cancer drugs that can be addressed because of the basic science knowledge obtained from the research that he, Kaelin and Ratcliffe conducted.

“Because oxygen is so critical to life, many of the common human diseases have derangements in their ability to maintain proper oxygen levels,” Semenza said. “When cancer cells become hypoxic, they turn on genes that enable them to invade, metastasize and spread throughout the body. Most chemotherapy drugs are developed to treat well oxygenated dividing cells, and there are none that are made to target hypoxic cells.”

Semenza identified renal cell carcinoma as an ideal first target for therapies that target hypoxic cells because kidney cells are known to express large amounts of EPO. Phase 1/phase 2 trials are underway to test their safety and feasibility, he said. – by Drew Amorosi

 

Reference s :

Maxwell PH, et al. Nature. 1999;doi:10.1038/20459.

Mircea I, et al. Science. 2001;doi:10.1126/science.1059817.

Semenza GL, et al. Proc Natl Acad Sci USA. 1991;doi:10.1073/pnas.88.13.5680.

William G. Kaelin Jr., MD 
William G. Kaelin Jr.
Gregg Semenza 
Gregg L. Semenza

Three scientists — two from the United States and one from England — have been awarded the Nobel Prize in Physiology or Medicine for their discoveries of how cells sense and adapt to oxygen availability.

The recipients — William G. Kaelin Jr., MD; Sir Peter J. Ratcliffe, MD; and Gregg L. Semenza, MD, PhD — were announced by the Nobel Assembly at Karolinska Institute in Stockholm during a ceremony earlier today.

Research done in the labs of these three investigators provided insight into how different oxygen levels regulate the body’s physiological processes.

“The seminal discoveries by this year’s Nobel Laureates revealed the mechanism for one of life’s most essential adaptive processes,” the Nobel Committee said in a press release. “They established the basis for our understanding of how oxygen levels affect cellular metabolism and physiological function. Their discoveries have also paved the way for promising new strategies to fight anemia, cancer and many other diseases.”

Kaelin is Sidney Farber professor of medicine at Harvard Medical School, professor of medicine at Dana-Farber Cancer Institute, and senior physician in medicine at Brigham and Women's Hospital.

His contributions to this year’s Nobel Prize focused on identifying the cellular components of the hormone erythropoietin’s response to hypoxia. The work led to the discovery of the hypoxia-inducible factor (HIF), a protein complex that binds to an identified DNA segment in an oxygen-dependent manner.

“Science today is not done by individuals but by an ecosystem,” Kaelin said during a press conference earlier today at Dana-Farber. “There are countless examples where my work has been made better not only by the people at Dana-Farber but by the fabulous biomedical ecosystem we have here in Boston.”

Kaelin dedicated the prize to his late wife — Carolyn Kaelin, MD — who was a breast cancer surgeon at Dana-Farber.

“Like most scientists, I occasionally let myself dream that this may one day happen,” Kaelin said, adding that he and his wife used to laugh about the idea of him winning a Nobel Prize.

Semenza is professor of pediatrics, radiation oncology and molecular radiation sciences, biological chemistry, medicine and oncology at Johns Hopkins University School of Medicine. He also is director of the vascular program at the Institute for Cell Engineering.

Semenza’s research on how cells sense and adapt to oxygen availability centered on the levels of erythropoietin and its response to hypoxia. It showed that specific DNA segments near the gene regulated the response to hypoxia in gene-modified mice.

PAGE BREAK

“This is an award that is shared by everybody at Johns Hopkins past and present, because I couldn’t have done it without my colleagues,” Semenza said during a press conference earlier today at Johns Hopkins. “I have been fortunate to have a long list of students and post-docs who have worked in my lab who have all contributed to this honor.”

Ratcliffe is the director for the Target Discovery Institute within the Nuffield Department of Medicine at Oxford University, as well as director of clinical research at Francis Crick Institute in London. His work examined oxygen-dependent regulation of the erythropoietin gene and showed that an oxygen-sensing mechanism was present in nearly all tissues.

“This discovery of how oxygen interacts with tissues is a powerful reminder of how the biggest discoveries come from the understanding of basic mechanisms,” George Q. Daley, MD, PhD, dean of Harvard Medical School said during today’s press conference.

“The discoveries made by [Kaelin] and his colleagues have fundamentally defined how cells respond to oxygen. ... Their work has broad application across a broad swath of medicine,” added Elizabeth Nabel, MD, president of Brigham Health.

Semenza was asked during the press conference what impact the science behind this year’s Nobel Prize in medicine will have for those suffering from disease — particularly those with cancer.

His response highlighted a deficiency in proper targeting among today’s cancer drugs that can be addressed because of the basic science knowledge obtained from the research that he, Kaelin and Ratcliffe conducted.

“Because oxygen is so critical to life, many of the common human diseases have derangements in their ability to maintain proper oxygen levels,” Semenza said. “When cancer cells become hypoxic, they turn on genes that enable them to invade, metastasize and spread throughout the body. Most chemotherapy drugs are developed to treat well oxygenated dividing cells, and there are none that are made to target hypoxic cells.”

Semenza identified renal cell carcinoma as an ideal first target for therapies that target hypoxic cells because kidney cells are known to express large amounts of EPO. Phase 1/phase 2 trials are underway to test their safety and feasibility, he said. – by Drew Amorosi

 

Reference s :

Maxwell PH, et al. Nature. 1999;doi:10.1038/20459.

Mircea I, et al. Science. 2001;doi:10.1126/science.1059817.

Semenza GL, et al. Proc Natl Acad Sci USA. 1991;doi:10.1073/pnas.88.13.5680.