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May 2011 Issue

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George Rieveschl Award for Distinguished Scientific Research for 2010: Peter Stambrook

Published May 2011

As an undergraduate student at Rensselaer Polytechnic Institute in New York, Peter Stambrook, PhD, switched from engineering to biology because, as he puts it from the safe distance of several decades, "I couldn’t draw a straight line.”

That may have been the last time he took the easy way out.

As the winner of the George Rieveschl Award for Distinguished Scientific Research  for 2011, Stambrook—a professor in the University of Cincinnati College of Medicine Department of Molecular Genetics, Biochemistry and Microbiology—is being honored for an approach that has typically led him away from the crowd as he sought insight into the mysteries of cancer.

The telltale phrases show up in his nomination letters for the award: "Contrary to dogma …”  "At a time when other investigators  …”  "Peter again is pushing the envelope.” And, in more than one letter, the C-word—in this case, creativity.

"I try not to follow the rules,” Stambrook says. "I tell my students and postdocs two things: One, don’t believe everything you read in the literature, because it may or may not be correct.

"Secondly, data that don’t fit your hypotheses are very often the most exciting data, because those are the data that lead you in new directions.”

Questioning began early for Stambrook, who became interested in DNA replication and cell cycle regulation as a graduate student. DNA replication is crucial to cancer research because DNA—which carries genetic information—has to be replicated faithfully to maintain integrity. Cancer results from replication errors, or mutations.

In his PhD thesis, Stambrook was the first to show that, in a vertebrate organism, the temporal sequence with which DNA duplicates itself, or replicates, can change during embryogenesis. At the time, the dogma was that DNA was an inflexible machinery for duplicating its genetic material and for transcribing that genetic material into RNA and then proteins.

Later, Stambrook took on another challenge regarding the nature and structure of replication origins. At a time when other investigators were studying replication in rapidly dividing invertebrate and amphibian embryos, in which the entire DNA replication phase is very short, making it relatively easy to visualize replicating molecules by electron microscopy, he chose to study mammalian cells even though the much-longer phase (six to eight hours) made the probability of seeing a replication structure extremely low.

By devising a novel approach involving selective heavy metal binding to the fork of the replicating molecule, Stambrook was able to observe the process and show that the mammalian cells also contained the tiny "replication bubbles” previously observed in the rapidly dividing embryonic cells.

Evangelia Kranias, PhD, Hanna Professor of Cardiology and chair of the department of pharmacology and cell biophysics at UC, wrote in her letter nominating Stambrook for the Rieveschl Award that these findings "changed the thinking in the field.”

Born in London to parents who were war refugees from Vienna, Stambrook grew up in Ithaca, N.Y., after the family moved to the United States to be closer to relatives. Shortly thereafter, he received a scholarship to attend Millbrook School, a small boarding school in the hills of New England. Following his graduation from Rensselaer, he earned a master’s degree at Syracuse University and his PhD from the State University of New York, Buffalo, and was a postdoctoral fellow at the University of Kentucky.

In 1981, after three years at the Carnegie Institution in Washington, D.C., and seven years at Case Western Reserve University, Stambrook joined the faculty at UC and turned his attention to a knockout mouse model that permitted the detection and quantifications of mutations in vivo.

Stambrook spent 28 years in the department of cancer and cell biology (formerly cell biology, neurobiology and anatomy), rising to acting chair in 1994 and then Francis Brunning Professor and Chair two years later after a national search. He joined the department of molecular genetics, biochemistry and microbiology in 2008.

Stambrook’s current research, funded by the National Institutes of Health, focuses on a critical signaling pathway that responds to DNA damage.  He also has recently formed a collaboration with the UC Brain Tumor Center to develop novel cancer gene therapy approaches.

"It’s a project I’m very excited about,” he says. "We’re looking at how to identify genomic rearrangements in a brain tumor, and then seeing if we can detect those rearrangements in plasma. If we can, that gives us a tool to look at the progression of the disease—and that’s a step in individualized medicine, which I think is the future of much of medicine.”

In other words, this researcher believes, the best is yet to come—and his nominators for the Rieveschl Award agree.

"With these ideas, Peter again is pushing the envelope,” writes Jan Vijg, PhD, professor and chair of the department of genetics at Albert Einstein College of Medicine. "More than ever, he is at the top of his game, with a great publication record, a consistently high scientific productivity and an unbelievably persistent, seemingly ever increasing dose of creativity in his approach to research.”

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