University of Vermont

College of Agriculture and Life Sciences

Wallace's DNA Research Sheds Light on Cancer's Origins and Potential Treatments

In September, Susan Wallace, chair of microbiology and molecular genetics in UVM's College of Agriculture and Life Sciences, received more than $9 million from the National Cancer Institute for a grant through 2015 to study individual human variants of the enzymes that repair DNA.

When Susan Wallace was a little girl, she remembers collecting specimens—newts, tadpoles, frogs and other creatures—with a friend of her father's who was a high school biology teacher. "I decided that I wanted to be a scientist from that time on, and everything I ever did education-wise was based on that," she says.

Today, Wallace is known worldwide for her contributions to DNA damage and repair—and for discoveries that have produced a greater understanding of the molecular processes that can ultimately lead to cancer. She is a UVM professor, chair of microbiology and molecular genetics, program leader of the Vermont Cancer Center's Genome Stability and Expression Research Program and one of the most prominent researchers in her fiel

Her work centers on the battle going on in our bodies, at the microscopic level, every day. We sustain 10,000 to 20,000 "hits," or assaults, per cell per day—simply because we breathe, says Wallace. A certain percentage of oxygen in our body becomes toxic, creating free radicals that cause oxidation and damage DNA. If this damage isn't repaired, it can lead to cell mutation and potentially, cancer.

Luckily, a group of enzymes—known as glycosylases—function as a repair team, patrolling the twisted strands of DNA, looking for lesions, or places where one of the DNA bases has been damaged. Wallace and her colleagues were the first scientists to discover the enzymes that recognize oxidatively damaged DNA bases in E. coli bacteria.More recently, her laboratory cloned, expressed and characterized three human versions of one of these enzymes, which perform the same reparative function in humans.

"We started out like all other molecular biologists doing things in E. coli because we could do them, and progressed to asking the same questions in human cells," Wallace says. "Interestingly, this particular repair system is highly conserved from bacteria to humans.... These systems were selected for, somewhere in the 'primordial soup' and have been preserved up through us."

Wallace's work has an important connection to the study of environmental causes of cancer-a key research focus for the Vermont Cancer Center, says Nicholas Heintz, interim director of basic science cancer research and UVM professor of pathology. "Her work focuses on repair of oxidative DNA damage, which is the predominant form of damage induced by endogenous, or internal, metabolism, inflammation and environmental insult

In September Wallace received more than $9 million from the National Cancer Institute for a grant through 2015 to study individual human variants of the enzymes that repair DNA. These variants, or proteins, may be present in a certain percentage of the population, and in some cases, have a greater likelihood of becoming pre-cancerous cells. The project will also look at variants of DNA repair enzymes in tumor cells-which could shed light on whether certain cancers will respond to radiation therapy or chemotherap

Throughout her career, Wallace has also been dedicated to mentoring and teaching. She teaches post-doctoral fellows as well as graduate, medical and undergraduate students. Her colleagues praise her many contributions to science, leadership and teaching. "She is an outstanding research scientist and one of the international leaders in the fields of radiation biology and DNA repair," says her colleague Philip Hanawalt, a professor at Stanford University specializing in DNA repair. "In recent years, she has been an invited plenary speaker and/or session chair at essentially all of the major conferences in the field."

Hanawalt also credits Wallace for being an exemplary role model for women scientists because she was one of the first women scientists in her field. Wallace recalls a site visit at her lab when she applied for her first NIH grant. "They said they'd never given a grant to a woman with children before, and they weren't sure they should," Wallace says. She got that grant-and she still has it. In fact, it has been honored twice by the prestigious NIH MERIT awar

Lynn Harrison, associate professor in the Louisiana State University's department of molecular and cellular physiology, says Wallace has been instrumental in supporting her career over the years. "To a young female graduate student, she set an extremely powerful and shining example as to what was possible for female scientists in what seemed to be a man's world," says Harrison, who later worked with Wallace as a post-doc. "She was a great mentor to me when I was in her lab and still is in many ways."

As Wallace manages the department that she founded in 1988, teaches students, mentors new researchers and conducts hands-on science, she appears to have carried through that enthusiasm and passion for science that she first developed as a young girl. When asked what she enjoys most, she says, "I think getting the answer to a long-standing question is the most fun. But asking the questions is pretty exciting, too."

This story first appeared in the Vermont Cancer Center's newsletter "Innovations."

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