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April 6, 2009 – (from Blue and Gray)

The Battle Against Drug Resistance
Paul Roepe’s Interdisciplinary Approach to Science Bridges Fields to Educate Young Minds

As a child, Paul Roepe’s interest in science blossomed from visits to his grandfather's small glass factory in Lyndhurst, N.J. He became fascinated with the complicated hand-blown glassware he saw and the stories he heard from his grandfather and glassblowers about how the combinations of the tubes and beakers were used by chemists at research and pharmaceutical companies. Those stories sparked his interest in the sciences and eventually led him into a world of research combining biology and chemistry.

Today, the professor of biochemistry and cellular and molecular biology takes an interdisciplinary approach to his own malarial drug-resistance work. He says it's an approach he learned early on and one he tries to instill in his students.

"When people ask me why am I so passionate about undergraduate exposure in my lab, (I tell them it's) because I feel I owe people," says Roepe, who also serves as chair of the chemistry department and co-director of the Center for Infectious Disease at Georgetown. "I had that experience at a very young age, and that's the kind of thing that really, I think, gets people off to a good start."

Roepe has had a number of disparate experiences that have led to his current research, one of which came during his undergraduate study at Boston University. Looking to make extra money in college, the chemistry major took a job as a bottle washer in a research lab at Massachusetts General Hospital. He found his interest in research growing as he worked in the lab, and he quickly progressed to more complicated tasks on the job. He conducted biopsies on rat kidneys and helped make monoclonal antibodies, which are identical antibodies produced by one type of immune cell.

After completing his undergraduate degree, he continued his academic path at Boston University by garnering a master's and doctorate in chemistry. His post-doctoral studies at the Roche Institute of Molecular Biology focused on bacterial membrane transport proteins that assist in the movement of substances across a biological membrane.

Just before Roepe began his postdoctoral work in 1986, researchers identified the multidrug resistant (MDR) gene that makes tumors drug resistant. It was one of a few hundred genes in the human genome that had been identified at the time -- there are now thousands.

“There were only maybe five or six labs in the country doing the sorts of things I was doing as a postdoc, and literally, all (of us) became experts in drug resistance because (we) played with the molecules that were the closest relatives to this newly isolated MDR protein,” explains Roepe.

Before his postdoctoral work, Roepe didn't know much about drug resistance, but he knew how to play with the molecules.

“I knew how to manipulate the membrane protein, to mutate it, to purify it, to put it back into an artificial membrane so that I could study it biochemically,” he says.

After completing his postdoctoral work, he went on to become an assistant member at Memorial Sloan-Kettering Cancer Center in molecular pharmacology and therapeutics while also serving as assistant professor of pharmacology at Cornell University.

Roepe moved his lab to Georgetown in 1997 and his research then shifted dramatically from mostly tumor drug resistance to mostly microbial. The switch occurred as funding for malaria-related drug resistance has increased over the last decade.

Malaria at the Lab

Roepe's lab at Georgetown is filled with postdoctoral, graduate and undergraduate students, and his malaria research projects fit into four areas: genetics, imaging, drug development and fitness. Over the past 15 years, he has received more than $10 million in research grants from the National Institutes of Health and the Burroughs Wellcome Fund.

The professor's expertise in biochemistry helped identify the chloroquine resistance transporter gene in Plasmodium falciparum, which is the species of malaria that most often kills.

He also helped develop the first inexpensive “high throughput” assay for screening antimalarial drug potency. The chemical testing is able to rapidly measure whether a new formula for antimalarial drugs will work. His discovery is now used by most malaria labs around the world and has been adopted by the U.S. military as their standard assay.

Roepe knows malaria isn't an epidemic in the United States and that he could be involved in other types of research, but he believes he's able to impact the most lives through his current research. Nearly 300 million to 500 million people are infected with malaria each year, according to the Center for Disease Control and Prevention.

“Nearly two million people, mostly children, die each year from this disease,” he says. “And there aren't enough people standing up for the research funding needed to fight it.”

The Collaborative Colleague

In addition to his work in the lab, Roepe commits a great deal of his time building bridges between departments and campuses. The chemistry department chair has collaborated with the physics and biology departments on Main Campus. By nature of his role as faculty in the School of Medicine's biochemistry and molecular biology
and the tumor biology program at the Lombardi Comprehensive Cancer Center, he is able to pull forces together between the Georgetown University Medical Center (GUMC) and Main Campus.

“He is a creative and original thinker who has interesting ideas on almost every subject,” says physics professor Jeff Urbach. “He's also a genuinely interdisciplinary scientist. He understands how to bring physics, chemistry and biology together to tackle the most challenging problems.”

In 2005, the National Institute of Allergy and Infectious Diseases awarded Roepe a five-year $1.1 million grant for his project, “The Physiology of Drug-Resistant Malaria.” He and Urbach are collaborating on new ways of imaging live malarial parasites within red blood cells. Their research has led to pioneering improvements to confocal microscopy. By using the high-tech microscope, Roepe's lab is able to rapidly image cells in four dimensions or three dimensions over time. The technology is now used in laboratories across the globe.

His energy and expertise is often noted by others. Biology professor Steven Singer says Roepe's passion for science is endless.

“In almost any meeting you have with Paul he works himself into a lather because he will never sit on his hands and keep it to himself.” Singer and Roepe co-direct Georgetown's Center for Infectious Disease with Richard Calderone, professor and chair of the department of microbiology and immunology at GUMC.

A Dedicated and Demanding Teacher

Urbach says Roepe's own intensity is infectious, and it spills over into the classroom.

“He cares deeply about science, but also about the people who are learning and doing science. When I sat in on his advanced biochemistry class, I watched him regularly challenge students individually to engage with the material,” he says. “At first I think they were terrified, but they learned to stay on their toes and keep up, and quickly understood that Paul was actually on their side.”

Former biochemistry student, Kateri DuBay (C'02) agrees. She recalls writing a paper that summarized the latest knowledge in an area of biochemistry of her choice. “A very challenging assignment for undergrads,” she says. “But it was really an accomplishment to struggle through the difficult language of the research papers and finally come up with a good synthesis of the research.”

DuBay received her master's in philosophy from Cambridge University in 2003 and is now doing her doctoral research in chemistry at the University of California, Berkeley. “In the lab, Dr. Roepe was tireless, animated, and always driven and excited to figure out something new about malaria or cancer,” she says. “I always came out of a science discussion with him feeling as if my head were spinning with all the new possibilities I needed to consider.”

Benjamin Vaccaro (C'06), now studying at Columbia University's College of Physicians and Surgeons, says Roepe's undergraduate biochemistry class helped equip him for medical school.

“Although demanding at times, I can honestly say that working with Dr. Roepe and my graduate student mentors prepared me more for medical school than any other class or extracurricular (activity) at Georgetown,” he says.

Roepe credits his graduate students for often taking undergraduates like DuBay and Vaccaro under their wings, giving them additional exposure to undergraduate research. He also continues to tell his students about the importance of approaching the sciences in a holistic manner.

“You can't approach science as a chemist or a biologist or a physicist,” he says. “You have to approach science as a scientist, and you have to think about problems. Don't think about approaches or techniques; think about problems.”

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