When Jack Summers’ research adviser encouraged him in his early days as a scientist to focus on the big questions, he hesitated.
“The big questions were the ones of societal importance that had eluded the best efforts of hard-working scientists for years,” said Summers in an article he prepared for a Western Carolina University 2011 research publication. “What, I reasoned, would make me think that I would succeed where others had failed? It seemed to me that it would be safer to choose easier targets and make slow incremental successes leading to publishable, if not important, results. Now, however, I can see she was right.”
Today as an associate professor of inorganic biochemistry at WCU, Summers is working with Lori Seischab, an assistant professor of biology, and WCU students on the big questions—questions at the interface of chemistry and biology that pertain to health, aging and disease. They are searching for compounds that inhibit an enzyme related to oxidative stress, and this type of stress, which may develop in any living organism that breathes oxygen, can lead to cancer, neurodegenerative diseases, heart disease and other health conditions. So far, their work has yielded some noteworthy findings and attracted support from the N.C. Biotechnology Center and the National Institutes of Health, which recently awarded the project a three-year, $325,000 grant.
“We hope at the end of the day that we will be able to come up with good, drug-like compounds that act against a specific enzyme,” said Summers.
When he first started working as a scientist, most research into oxidative stress focused on its effects on whole cells and large biological macromolecules, but he was interested in researching what was happening at a smaller, molecular level. A senior scientist for whom he worked, however, told him that the chemistry had been worked out for years and that such research would be a waste of his time.
It was not until 2003 when Summers was hired to teach at WCU and began considering what research to pursue on his own that he revisited the topic. The more he read, the more he came to believe the logic supporting established theories was flawed, and research he conducted in WCU’s labs supported a different hypothesis. In 2007, Summers and a group of co-authors published their results on the origins of reactive oxygen species in the Journal of the American Chemical Society.
“The paper we published had important implications for oxidative stress and pointed a clear way forward for developing drugs targeted towards specific metal containing biomolecules,” wrote Summers. “After exploring a few dead ends, we selected a target for our drug development efforts, namely members of a family of enzymes called superoxide dismutases.”
The research was initially supported by a summer undergraduate research fellowship program. With funding from grants designed to help WCU implement its Quality Enhancement Plan, the program provided stipends and supplies for chemistry students to work with faculty on their research in 2008. Mickey Yost, a 2009 graduate, worked with Summers to further examine whether natural products called flavonols, which occur in such foods as broccoli and onions, inhibited the target enzyme. Yost shared in a reflection paper that the experience taught her not just how to do a laboratory test, but why.
“My mind was able to work differently,” said Yost, who is now a clinical technologist with Duke University Health System. “Before, I was able to do a test and tell you what the result was. Now I’m able to wrap my head around a process and come up with new ideas and possibilities, then think of ways to test them.”
Summers said the students’ findings provided information that he and Seischab used when they applied for and won a $67,000 grant from the N.C. Biotechnology Center. Findings from the subsequent research helped them win the recent NIH Academic Research Enhancement Award.
Today, Summers and chemistry students continue conducting research to identify compounds that might be good candidates for inhibiting the target enzyme, and Seischab and biology students test the effectiveness of compounds identified at a cell-based level.
“We see what happens if we introduce the compound to bacteria,” said Seischab, whose graduate and post-doctoral research centered on inflammatory diseases in which oxidative stress plays a major role. “I have always been interested in research related to developing possible therapeutics for diseases – projects where patients may see the benefit of your work – rather than studying basic mechanisms.”
Summers said in his 25 years as a scientist that this is the most exciting work of which he has been part.
“We have not yet published about our latest research results, but we’ve made a lot of progress,” said Summers. “We are trying to give back and do something helpful for society.”