Charis Eng, AB’82, PhD’86, MD’88, discovers key genetic markers linking cancer and autism.
Some people have trophies; geneticist Charis Eng, AB’82, PhD’86, MD’88, has empty wine bottles arranged on a high shelf in her office at Cleveland Clinic’s Lerner Research Institute. The budget-minded Seaview Brut and Roeder Estate hark back to the late 1990s, when Eng and her colleagues at Dana-Farber Cancer Institute toasted her discoveries around PTEN, a gene linked to a tumor-causing disease called Cowden syndrome. “We were poor then,” says Eng, the chair and founding director of the Cleveland Clinic’s Genomic Medicine Institute, with a twinkle behind her silver-rimmed glasses. Rouge Homme 1985, an elusive claret, was poured in honor of findings on RET, another tumor-related gene. Eventually, confesses Eng, “we published so many papers that I stopped this. I said, ‘If we drank a bottle every time we published a paper, we’d be drunk all the time.’” Postdoc work at the University of Cambridge, where Eng was the lone woman in a sea of men, spawned her interest in the grape. In England the drinking culture was huge, she says. “The old boys wouldn’t even collaborate with me if I didn’t know my wine.” So she began reading Wine Spectator and going to free wine tastings at local shops on Saturdays. “So, I’d read and taste. After one year, they said, ‘Boy, you’re so good we want to invite you to the wine committee.’ That’s the committee that picks wines for the college. It’s a huge deal. Unfortunately, they tasted on Mondays at 10 a.m. But I’m like, I’m in the middle of my work!” An effervescent presence in the church-like halls of Lerner Research Institute, Eng has made a name for herself with her discoveries of several key genetic links to Cowden syndrome, a disease characterized by the spread of benign tumors. Cowden patients with the PTEN mutation have much higher incidences of colon, thyroid, and breast cancers. In the 1990s Eng discovered the first PTEN gene mutation associated with Cowden. Later she and her research team found that patients with the PTEN mutation and an epigenetic alteration called KILLIN have even higher cancer risks. Eng’s findings have led to early screening for Cowden patients who carry the PTEN or KILLIN mutations. For instance, thyroid cancer tends to show up in PTEN patients at a much younger age than in the general population. “With our recent 2012 study, the youngest age of thyroid cancer is six years old,” says Eng. “So the moment you find a PTEN mutation, we start screening the thyroid.” Back in the bargain-wine days of her career, Eng had a tough time landing research funding. “As [UChicago oncologist] Funmi Olopade herself said, I was a translational investigator before the word ‘translation’ came into being,” she says. Translational medicine is an interdisciplinary approach to research where findings in the lab don’t exist in a vacuum but are closely linked with clinical observation and improving patient care. The National Institutes of Health “kept saying ‘Where’s your mouse model?’ I don’t care. I’m looking at the patients. … They couldn’t get their heads around that.” Her first funder was the American Cancer Society (she’s an ACS professor now) and then others came around. Sitting at a round table in her office, amid a smattering of gifts from colleagues over the years—glass animal figurines and pillows embroidered with goofy sayings—Eng says she learned the importance of connecting with patients from growing up around her “number one uncle,” the personal physician of the founding prime minister of Singapore. He made rounds every day, even off days. She did the same as an internal medicine physician and oncologist. “My patients loved it,” she says. “There’s none of ‘Oh, the regular doctor’s not here.’ Horrible things happen on weekends.” When she was a teen, Eng’s family moved to the United States so her father, Soo Peck Eng, PhD’72, could work on his doctorate. She enrolled in the University of Chicago Laboratory Schools, where she caught the genetics bug from biology teacher Murray Hozinsky. Her father had to return to Singapore after two and a half years, but she managed to stay in the United States by dropping out of Lab early and starting in the College at age 16. Professor Michael Blackstone, “a man so smart he frightens chairmen of medicine,” taught her the complexities of tumor-causing syndromes. “I said ‘Oh boy, these lumps and bumps, they seem to affect every layer of the germ cells,’” she recalls. “And so it must be a very important gene not only for cancer development” but for normal development as well. “And in retrospect, the PTEN gene is vital for human development.” That’s why when it mutates it not only gives rise to cancers but is associated with autism, a neurodevelopmental disorder. In 1999 Eng was recruited to lead the human genetics division of Ohio State University’s internal medicine department. A few years later, she began noticing that a significant number of patients in her Cowden cohort there had children with autism. So she “called up all my friends who are developmental pediatricians”—this is the sort of collaboration that fuels her research—and asked for tissue samples on their autistic patients. She found that 10 percent of patients with autism and large head circumference had the PTEN mutation. Eng’s finding, along with research by others into a disease called tuberous sclerosis, in August 2014 resulted in partial funding from the National Institutes of Health for a clinical trial of a tumor-suppressing drug in autistic children who have the PTEN mutation. Eng arrived at the Cleveland Clinic in 2005, on the condition that she could start a genetics institute where physicians and scientists interact across disciplines. “Most places have a small cancer genetics initiative in the cancer center,” she says. “Then they have pediatrics balkanized away, then they have prenatal balkanized away. And nobody talks.” She wanted a broad platform of genetics for everyone: science, clinical work, education. “The original searching was just for a basic science department. I said, ‘Let me show you my vision. Can I do this?’ And they said yes.”