Yiyu Zou, Ph.D., studies the inhaled drug azacytidine for preventing lung cancer. It acts epigenetically—i.e., it strips off methyl groups that silence cells’ tumor-suppressor genes. An associate professor of medicine (oncology), Dr. Zou earned master’s and Ph.D. degrees in his native China, and did postdoctoral work in cancer pharmacology and experimental therapeutics at the M. D. Anderson Cancer Center in Houston before coming to Einstein in 2002 with his research colleague, Roman Perez-Soler, M.D.
How did you get interested in lung cancer?
One reason was my father, a heavy smoker who lost 80 percent of his lung function before dying of lymphoma at age 65. I also saw that a lot of people in China were developing lung cancer, and I thought, “I have to gain the knowledge to fight this disease.”
Could you describe your research for us?
One of my projects looks at how environmental carcinogens cause lung cancer. I developed a mouse model in which we mimic human lung cancer by continually injecting tobacco carcinogens into the mouse lung for more than a year. We saw the classic precancerous stages and, after nine months, tiny cancer nodules. When we administered aerosolized azacytidine along with the carcinogens, only half the mice developed tumors. We are submitting an Investigational New Drug application to the Food and Drug Administration for testing this therapy on people.
What gave you the idea to try an aerosolized drug against lung cancer?
Tobacco carcinogens can damage epithelial cells that line the airway. Azacytidine can potentially reverse the epigenetic changes, which precede the genetic changes. And using azacytidine in aerosol form means it comes in contact with all those epithelial cells directly affected by tobacco smoke.
Why do you view your drug as preventing lung cancer rather than treating it?
This method won’t work against large tumors already in the lung. Instead, we’re aiming at an earlier stage, when thousands of epithelial cells of a smoker’s airways have those potentially reversible epigenetic abnormalities. Such a therapy could prevent smokers from developing primary tumors and prevent lung cancer patients from developing what we call second primary tumors.
You’re known for the unique way that you hold mice.
When you touch mice, you have to be nice. I hold mice in my whole hand, just like you’d hold a small pet, and I make them as comfortable as I can. If they want to bite me they can, but they rarely do. These mice contribute much to humanity, so we must help them live comfortably.
Did you meet your wife here at Einstein?
Yes, my wife was an Einstein M.D./Ph.D. student. What brought us together were our common interests: sports and classical music. We went kayaking, rollerblading and skiing and played tennis together. And after we got married we had subscriptions to concerts at Carnegie Hall for a couple of years.
What happened then?
Our son, An Ping, was born. He’s now almost three. His name means “safe and quiet.” But he’s certainly not quiet!