Every morning Clyde Denis enters his laboratory in Rudman Hall with the expectation that, before the day is through, he might learn something that nobody ever knew before. That’s why he’s a molecular biologist, he says: because we know so little about life, and there is so much more to discover.

For the past 19 years, Denis, a professor of biochemistry and molecular biology, has been investigating how cells function and why cancerous cells grow uncontrollably. Most recently, he has focused on two proteins manufactured by cells that appear to turn off that growth. In the past 19 years, the National Science Foundation and National Institutes of Health have given him more than $5.6 million to continue this promising line of inquiry.
Denis works with yeast cells, which function like human cells but are quicker and easier to grow in the lab. Further work must now be done with human cells, but his research could lead to novel drugs or gene therapies to suppress cancer.

Denis became intrigued by the possibility of discovery in a high school biology class, but it wasn’t until he took organic chemistry and microbiology at the University of Illinois in the early 1970s that he abandoned his plan to become a physicist. As an undergraduate he was strongly in�uenced by Carl Woese, one of his professors. Woese studied bacteria living in extreme environments— at the bottom of the deep ocean, for example— and found what many scientists now agree is a whole new kingdom of living things.

“He was always thinking, creating questions, formulating hypotheses,” Denis says. “That’s what I liked about the scientific process.”

Denis has spent his own career figuring out how cells know what proteins to produce, when to produce them, and when to stop. That’s critical because most cell functions are carried out by proteins.

The proteins that a cell produces are determined by the genetic coding stored in the double helix of DNA in the cell’s nucleus. DNA provides the original template for the production of messenger RNA which, in turn, serves as a template for the production of proteins. Ordinarily, the cell keeps producing a particular protein as long as it needs it and then stops. Denis has been looking for the mechanism that turns off the protein production. Working with a colleague at the University of Arizona, he has recently shown that two proteins, CCR4 and CAF1, act together to trigger the breakdown of RNA and stop production. Both proteins occur in human cells, so this discovery could ultimately lead to a new method of tumor suppression in humans.

Research is painstakingly slow and often takes decades to lead to a breakthrough. Denis first isolated CCR4 in 1981 and is still investigating exactly how it is regulated. Yet he remains as excited about the opportunities for generating new knowledge today as he was when he started studying biology as a teenager. “Science is all about making those connections,” he says. “All we’re limited by in science is our imagination.”

—Maggie Paine,
UNH Alumni Publications