When Song Wang began a year of laboratory rotations in UCLA's ACCESS program, seeking a place to do his doctoral studies, it wasn't just the scientific ideas that interested him. He wanted a setting that wasn't too crowded with other apprentices. "If you go into a humongous lab, there are a whole lot of postdocs and graduate students," he explains. "An entering-level graduate student can often get lost," missing opportunities for mentoring and interesting work. Song also sought an expanding area of research where he could "perform good experiments and move on to the next stage in my career."

Oliver Hankinson's laboratory in the Department of Pathology and Laboratory Medicine met Song's criteria. Its postdoctoral fellows and graduate students were looking at a number of interesting questions about how environmental pollutants including dioxins and polycyclic aromatic hydrocarbons (PAHs) cause toxic effects at the cellular level. These compounds, which have received a lot of attention in the mainstream press, are created by a variety of natural and manmade events, from brush fires to automobile exhaust and cooking of food, and they move through the food chain from soil to animals to humans.

Dr. Hankinson had discovered a protein called ARNT which associates with the aryl hydrocarbon receptor (AHR) and dioxins in the nuclei of cells. The AHR / ARNT combination (called a dimer) attaches itself to a chromosome and regulates gene activity. This process drew Song's attention. He looked at how AHR and ARNT regulate certain metabolic enzymes as well as the expression of other genes, including those that regulate cell proliferation.

The enzymes have "good intentions," he says: They work on PAH molecules to make them water soluble and thus easy for the body to eliminate. However, when they are out of balance, the enzymes cause accumulation of highly reactive metabolic derivates of PAHs, which can then lead to mutations and cancer. The presence of dioxin, which resists breakdown, probably triggers the prolonged activation of the genes involved in cytokine production and cell proliferation.

"We haven't answered all the questions about how that happens yet," Song says, "but we're trying hard." In the meantime, findings of the studies he's participated in have been published in several top-rung journals.

Song has been the first to apply several new techniques—for example, ChIP (Chromatin Immunoprecipation) assay and RNA interference procedures—to studies on the mechanisms of dioxin and PAH carcinogenesis, and he is continuing to reap the rewards of these innovations, Professor Hankinson says, calling this "a major achievement of his work." In addition, Song "reads voraciously," Professor Hankinson says. "He is probably more apprised of recent developments in mechanisms of gene transcription than myself. His suggestions are routinely penetrating and useful."

Song says he enjoys the process of "looking through the abundance of existing knowledge to find a niche where you can develop a contribution," he says. "That's a fun thing for me to do." He's grateful to Professor Hankinson, not just because he "has provided a lot of support and guidance," Song says, but also because he encourages "a degree of intellectual independence in the lab" that Song believes is "quite important for training future independent investigators" and thus achieving his career goal. Professor Hankinson is confident that Song "has the potential to develop into a first-rate independent investigator."

At the moment, Song is reviewing opportunities to do postdoctoral research unrelated to his dioxin studies: in stem cells, tumorigenesis, or neuroscience. Then, he thinks, a research position in the pharmaceutical industry might complete the American period of his resume.

Song hopes someday "to transplant some of this knowledge back into China," where he grew up in Tianjin, a major city not far from Beijing. When he was a boy choosing a career direction, bright students like himself were often steered toward science. Although this wasn't done "forcefully, without asking my opinion," Song acknowledges that a science career was not entirely his choice. It was just that careers in business and law had not developed in China to the extent they have today.

The academic environment in China continues to grow, Song says. At one time, Chinese scholars might have remained in the West because that was the only way to access the resources they needed to do their work. "Now, China is developing so fast that in a few more years, there may be a very good environment for science," he says. It's an environment that appeals to Song. "I would like to contribute to the development of my country," he says, "perhaps the development of its health care system."

When Song was in high school, he chose basic biological science over medical school, with consequences he's come to appreciate. While clinical research is valuable, he says, it is basic scientists who are "going deep into the molecular mechanisms" of diseases, where causes can be identified and cures developed.

Published in Spring 2003, Graduate Quarterly