A Profile in Persistence
By Matthew Kincanon (’19)
Gonzaga News Service
SPOKANE, Wash. — Professor Jennifer Shepherd, chair of the chemistry and biochemistry department at Gonzaga University, has been researching since 1998 to find new ways to treat parasitic infections, a Third World epidemic.
The effort is a marathon, not a sprint. Shepherd’s work is a profile in persistence, dedication and tenacity as each hard-won breakthrough brings her a step closer to better, more effective treatments.
“I have been working on this project since I started my faculty position at Gonzaga, and it has changed directions many times as new technology and instrumentation has become available,” said Shepherd who has made significant strides toward addressing a problem that the World Health Organization estimates is responsible for sickening some 1.5 billion people worldwide at any given time.
“We have had several breakthroughs, but each one takes many years to explore.”
She remains undeterred in her war against these insidious invaders that can infect people without them knowing what is making them sick. Untreated, parasites can cause severe malnutrition and a host of serious physical and cognitive impairments including irritability, chronic fatigue, rashes, sleep problems, anemia, muscle cramps, allergies, poor concentration, and headaches.
“Many people don’t recognize that parasitic infections are an epidemic since they occur primarily in Third World countries. However, these infections are among the most neglected tropical diseases,” Shepherd said. Exacerbating the problem, new treatments take years to develop. Only four anti-parasitic drugs have been brought to market since 1975, and parasites have developed resistance to many treatments.
In 2010, Shepherd herself contracted a parasitic infection while living in Ghana for three months during the adoption of two of her three children from an orphanage there.
“It definitely became more relevant to me when I experienced an infection firsthand, and even more so because I actually saw many children and adults suffering from severe infections in Ghana,” said Shepherd, who purchased “dewormer” medication for the entire orphanage a few times.
Shepherd, who has been to Ghana seven times, said her Ghanaian friends were excited to hear about her research.
“Some of the older kids at the orphanage recognized when they had severe infection symptoms and knew when they needed treatment,” she said. “I will never forget the image of these kids. It personalized the research for me.”
Rhodoquinone biosynthesis, an essential process for parasites to survive in people, has been identified by Shepherd as a unique pathway for drug design. Current anti-parasitic treatments target the energy systems of both parasites and people, some of which can have negative side effects including dizziness, hair loss, seizures, signs and symptoms of liver injury and other problems.
Paloma Roberts Buceta, a senior biology major doing research with Shepherd, said parasites are responsible for significant socioeconomic consequences as well. Like many health problems, the poor tend to be disproportionately harmed by parasitic infections as children underperform in school and adults are unable to work, locking them in a cycle of poverty.
Shepherd’s research focuses on helminth parasites, which include tapeworms, flatworms and flukes — the most infectious agents of humans in developing countries. They typically are found in the intestines, but can move into the lungs, liver, blood and other parts of the body.
In 2012, Shepherd and her colleagues discovered a new gene, named “rquA,” which is required for rhodoquinone biosynthesis in a bacterial model system. If the gene is mutated or deleted from the genome, rhodoquinone cannot be produced and the bacteria can’t survive in the absence of oxygen, she said.
“Humans don’t have rhodoquinone, they don’t make it, they don’t need it, so the idea is to selectively stop the parasites from making it and then they can’t survive inside a host,” Shepherd explained.
Currently, researchers are using a nonparasitic worm model that produces rhodoquinone and is similar to the parasites. In the last two months, they found another gene target that is required to make rhodoquinone in the worms, which may lead to even stronger results.
Through her research, which has received funding from the National Science Foundation, the National Institutes of Health, and Research Corporation, Shepherd has also worked with dozens of GU undergraduates and faculty, and researchers from such institutions as the University of Florida, UCLA, Dalhousie University in Canada and the Institut Pasteur de Montevideo in Uruguay — the latter has been sending samples to Shepherd for testing.
“We can’t do everything here at Gonzaga, but we’re making an impact and when we do come up with an inhibitor, we can then move it to a group that’s actually working with the parasites; we have model systems that work well here,” Shepherd said.
Her most recent research involving a dozen GU undergraduate co-authors has been submitted this fall for publication to two peer-reviewed journals.
“We are doing important work at Gonzaga to combat global health issues, and our undergraduates are doing the majority of the experiments right here on campus,” Shepherd said. “Our results have the potential to make a big impact on the treatment of parasitic helminth infections in the future.”