Connecticut College Magazine · Summer 2012

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Former Dean of the College Jewel Plummer Cobb with Beverly Clark Prince '72 in Cobb's lab at Connecticut College. Photo courtesy of the Linda Lear Center for Special Collections and Archives.

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Studying the cell's gatekeepers

Studying the cell's gatekeepers

Today's research by Heather Pinkett '97 could help her mentor's grandson tomorrow

by Julie Wernau


For some cancer patients, chemotherapy treatment isn't an option. Their cells reject the drugs, dumping them before they can destroy the malignant material. Heather Pinkett '97 is working to change that.

An assistant professor of molecular biosciences at Northwestern University, Pinkett is one of only a few researchers in the world studying the structure of proteins in human cells called ABC transporters. These transporters are embedded in the walls of cells and act as pumps — carrying materials, including medicine and toxins, across cell membranes.

“In general, membrane proteins are the cell's gatekeepers, controlling how compounds get into or out of cellular compartments. It's the cell's first line of defense,” Pinkett says.

But very little is known about why ABC transporters reject helpful medication in some patients and not others. Of the more than 1,000 transporters identified in all living things, the structure and details of just eight of them are known. Yet their ramifications are profound for everything from the treatment of cystic fibrosis to everyday infections: The growing resistance to antibiotics stems from the same transporters, which are increasingly able to recognize and pump out lifesaving drugs.

“Membrane proteins represent over 50 percent of drug targets, but we know very little about the structure — what they look like,” Pinkett says. “I wanted to focus my research on an area that would have a huge impact on human health. What's the next big question — something that's going to be relevant for the next 20, 30, 40 years?”

For David Lewis, the Margaret W. Kelly Professor of Chemistry and Pinkett's first research mentor, Pinkett's work recently became personally relevant. His 3-year-old grandson was diagnosed with an extremely rare ABC transporter mutation and has to spend much of each day on supplementary oxygen because the mutation negatively impacts his lung functioning.

“I was completely blown away. That personal link, it's the kind of information that pushes me on,” says Pinkett, who counts Lewis as one of a handful of people who have profoundly influenced her career.

As a freshman at Connecticut College, Pinkett didn't set out expecting to major in biochemistry. But a psychology class that touched on the biology of the brain left her itching to learn more.

Lewis says Pinkett was an average student in his analytical chemistry class, but he saw her potential. Women and minorities are often underrepresented in the sciences, Lewis says, because they encounter barriers and may be reluctant to ask for help — a subject he has researched extensively. The summer after Pinkett's junior year, he offered her a chance to conduct research with him at Colgate University.

“It was an amazing research experience and the start of my research career,” Pinkett says.

Lewis stayed in touch with Pinkett after graduation, when she entered the Postbaccalaureate Intramural Research Training Award program at the National Institutes for Health, where she was a researcher in biomedical sciences. Later he and his wife visited Pinkett while she was earning her Ph.D. in biochemistry and molecular biophysics at the University of Pennsylvania School of Medicine.

“In a chemical reaction, catalysts lower energy barriers so molecules can get over those barriers faster,” Lewis says. “My job as a teacher and research mentor is to lower the barriers so that students who have potential can get over the hang-ups in the way of their reaching that potential. Everything Heather has accomplished is the result of her efforts and her intelligence and her people skills. She's on fire.”


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