Hutch News Stories

Groundbreaking discoveries in gene regulation in mammals make Groudine a 'deserving' choice for national academy

Drs. Michael Emerman, Steve Hahn and Mark Groudine
As colleagues (from left) Dr. Michael Emerman, Steve Hahn and others look on, Dr. Mark Groudine expresses his appreciation for becoming a member of the National Academy of Sciences, during an afternoon reception in the Double Helix Cafe on May 1. Photo by Theresa Naujack

Dr. Mark Groudine's election to the National Academy of Sciences "couldn't have happened to a nicer or more deserving guy."

That's the assessment of Dr. Lee Hartwell, Center president and director, who also is a member of the distinguished group. "

Mark has made important contributions to our understanding of gene regulation in mammalian cells," Hartwell said, "and he continues to be at the forefront of that field."

The academy May 1 named Groudine, director of the Hutch Basic Sciences Division and a professor of radiation oncology at the University of Washington, to membership in the nation's most prestigious scientific organization. He was among 72 new members and 15 foreign associates from 10 countries recognized for distinguished, continuing achievements in original research.

"It's quite an honor to have the body of work from the lab recognized in this way," Groudine said. "I have had wonderful students, postdocs and collaborators, and it is their contributions that are being recognized. I've also been fortunate to have the support of the Hutch and the UW in pursuing my research and clinical interests."

1,874 members

Those elected this month bring the number of active academy members to 1,874, including Hartwell, Dr. E. Donnall Thomas, director emeritus of the Clinical Research Division and 1990 Nobel Prize winner; and Dr. Robert Eisenman of the Basic Sciences Division. Dr. Hal Weintraub, founding member of the Basic Sciences Division who died in 1995, also was a member.

Groudine has made crucial contributions to the understanding of how genes are regulated in mammalian cells. He developed techniques for studying gene regulation and discovered elements that help regulate the expression of large regions of chromosomes.

Eisenman, who has known Groudine since 1972 when they worked at the Swiss Institute for Experimental Cancer Research in Lausanne, said his colleague has opened up new fields of study.

"Mark found a fundamental role for chromatin structure," he said, referring to the protein complex that helps package DNA into chromosomes. "People knew DNA was wrapped up in proteins, but Mark made the connection that chromatin structure is important for gene regulation."

Much of Groudine's work has centered on the study of regulation of the beta-globin genes, which instruct the cell to make a protein component of hemoglobin, a molecule that transports oxygen in the blood. Regulation of the cluster of beta-globin genes is complex, as different forms of the protein are synthesized in the embryo and adult.

Groudine was the first to show that the form of beta-globin synthesized during different developmental stages is due to changes in gene activation rather than the synthesis of globin proteins from preexisting RNAs, the intermediary molecules with instructions for protein synthesis.

With Weintraub, his longtime friend and colleague, Groudine developed important methods, using enzymes called nucleases, for studying the physical differences between active and inactive genes.

Dr. Paul Neiman, an investigator and former director of the Basic Sciences Divison who helped recruit Groudine to the Hutch in 1979, called his colleague a "pioneer in the field of gene regulation."

"Mark identified a number of major regulatory elements, such as the locus control region (LCR), that control expression of genes," he said.

In the mid-1980s, Groudine was among the first to describe the LCR, a DNA element important for preventing the inactivation of genes. He showed that defects in the beta-globin LCR can result in a blood disorder known as thalassemia.

Later, Groudine showed that an LCR involved in regulating immunoglobulin genes is involved in the inappropriate maintenance of myc gene expression in Burkitt's lymphoma, a cancer involving unregulated division of B-cells.

In his studies of myc, a gene whose synthesis is disrupted in a wide variety of cancers, Groudine was the first to identify another novel mechanism of gene regulation, called attenuation, in higher cells. Until this discovery, it was thought that the rate-limiting step in the activation of mammalian genes was the binding of an enzyme, RNA polymerase, to the start of the gene.

But Groudine showed in the human myc gene that while polymerase binds, its progression down the gene can be blocked. Groudine and others have shown that many genes, particularly those that respond rapidly to changes in the cellular environment, are regulated this way.

In addition to lab research, Groudine, a radiation oncologist, sees patients each week at the UW and is nationally recognized for oncological expertise.

"Mark is an extremely respected and recognized leader in American biomedical science and has held positions on a number of important medical regulatory boards," Neiman said.

Appointed division director in 1995, Groudine wins high collegial praise. "He's so interested in everything and sees things with a lot of depth," Eisenman said. "Anytime you talk to Mark about your work, you come away feeling excited."

Supportive mentor

Hartwell also commended Groudine for his reputation as a supportive mentor and colleague.

"One of the things that is particularly gratifying about Mark's election into the academy is that he is not a self-promoting person," he said. "He puts the careers of his postdocs, graduate students and colleagues above his own credit."

The academy is a private organization of scientists and engineers dedicated to the furtherance of science and its use for the general welfare. It was established in 1863 by a congressional act of incorporation, signed by Abraham Lincoln, that calls on the academy to act as an official adviser to the federal government, upon request, in any matter of science or technology.

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