5 Questions with an Expert on Cell Death

Did you always hope to have a career as a scientist?

At one time I had no idea that I would even go to college. I grew up in China during the Cultural Revolution, when most colleges were closed for more than ten years.

I had a high-school teacher who believed I should go to college. But the middle-school education I had received had not prepared me for the exams. What was worse, I had no textbooks for study. My high-school teacher helped me; he stole textbooks from the library so that I could study. I did and scored number one in Shanghai. This ranking earned me the opportunity to attend Fudan University in Shanghai.

What inspired you to study regulated cell death?

During my second year of graduate school at HMS, I took a class about neurodegenerative disease and became curious about how a cell dies. I learned that these diseases are caused by the death of specific neurons, not by a total loss of neurons. I wondered how one population of neurons could be affected while others remained mostly okay. Since selectivity in biology means regulation, I thought that cell death must also be regulated. But most people in the field then were interested in studying suppression of cell death, not about how cells die. I decided I wanted to study cell death.

How did you manage to do research at MIT when you were a student at Harvard?

It was hard to find a faculty mentor who was researching cell death. By chance I attended a seminar by H. Robert Horvitz from MIT on programmed cell death in the nematode Caenorhabditis elegans. Most people paid little attention to C. elegans at the time: How can a little worm be relevant to humans? But it was the only model I could use to study cell death, so I joined Horvitz’s lab.

Has this research taken you in unexpected directions?

Yes. I’m now investigating necrosis, a common aspect of human disease that many have considered to be passive cell death and, therefore, unregulated. We observed a form of necrosis that was regulated and discovered a molecule with drug-like properties that targets the enzyme involved in that regulation. This discovery has led to studies of the mechanism of necrosis and its role in human disease.

What compels you to question the dogmas about processes such as regulated cell death and necrosis?

As a scientist, you must dig deeply. It’s difficult to remain confident when you’re working in an area that most consider well defined, but that you think remains unknown. You ask: Is my hypothesis correct? But no matter what, you must go ahead and test it. You must have confidence in yourself.

Image: John Soares