Profiles in Cancer Research
Dr. Jun S. Wei
Staff Scientist, Oncogenomics Section
Pediatric Oncology Branch, NCI's Center for Cancer Research
Dr. Jun Wei’s journey into cancer research began in the 1980s in Shanghai—a cosmopolitan cultural center of China, the first country in history to reach a billion people, and a society just beginning to emerge from the Cultural Revolution. Jun Wei, teenaged son of a physician and a chemical engineer, was thinking about science.
“The idea of our generation was if you have talent or potential you study science or engineering, because not everyone can do that,” he explained. “You are encouraged from the time you’re very young.
“Coming to the United States for college was not that common in the ‘80s,” he said, though some of the practical and financial hurdles were lowered because his uncle’s family was already well established in Houston. One of his uncle’s daughters, Victoria, was around Jun’s age and still in college. The two became very close, and his cousin helped him to assimilate into the new culture as Jun began his studies in biology at the University of Houston.
After becoming more fluent in English and working hard in college, he won a scholarship in 1992 to the Baylor College of Medicine. “In the early 1990s I saw that ‘molecular’ was becoming a buzzword,” recalled Dr. Wei. “I can’t say at that time that I had ‘the big picture’ of a career in mind, but looking back, getting into molecular biology was a good choice.”
For someone who would go on to become a leader in a diverse, active genomics laboratory, the cardiovascular sciences program in the DeBakey Heart Center proved to be the ideal training ground. During the mid-1990s he studied molecular and cell biology, while at the same time becoming fascinated by the emergence and promise of molecular tools like DNA microarrays.
Dr. Wei’s graduate school training in the 1990s coincided with a dramatic change in the potential of molecular biology. In biomedical research, a genome-wide hunt for disease-causing genes was afoot, even if searching for those genes remained difficult at the molecular level. Current NIH Director Dr. Francis Collins was at the helm of the National Human Genome Research Institute (NHGRI) at the time, driving toward the goal of decoding the human genome. Microarray technology was just about to take off, and Dr. Paul Meltzer’s laboratory was one of only a few at NIH (and the world) using that approach to study cancer genetics.
So in 1999, Ph.D. in hand, Dr. Wei answered an NHGRI ad in the British journal Nature for a molecular biologist to study Ewing sarcoma, an uncommon pediatric bone and soft tissue tumor. The senior research fellow he would be working with was Dr. Javed Khan, a Cambridge-trained physician-scientist who had been doing early work at the Sanger Institute in cytogenetics, who began to tutor the junior postdoc in the budding art and science of using microarrays.
The connection would prove to be symbiotic, as Dr. Khan quickly realized. “Jun had an impressive command of a wide range of cell and molecular biology techniques,” he recalled.
“You have to remember,” said Dr. Wei, “in those days, fabrication of microarrays was not yet perfected. We had to basically build them from scratch.” This was a daunting, painstaking process, sometimes requiring hundreds of steps, reliant on judgment, keen observation, and a deft manual touch for manipulating a miniature world that was sensitive to temperature, humidity, and other vagaries of the laboratory environment. “Everything you can imagine could and often did go wrong,” said Dr. Wei.
“But Jun was quite amazing, very adept working in that world,” countered Dr. Khan, who persuaded his lab partner to come with him 2 years later when he moved to NCI to head the Oncogenomics Section of the Pediatric Oncology Branch in the Center for Cancer Research.
Genomics in the Trenches
For nearly a decade now they have been partners and collaborators. Dr. Wei runs Dr. Khan’s lab, one of only a few in the branch using these advanced oncogenomic approaches to study cancers like rhabdomyosarcoma and neuroblastoma.
“You could see that genomics was just taking off when we first started working together, and it was really exciting to get in at that early stage,” said Dr. Wei. “At the time we were actually printing our own DNA microarrays, using what was then cutting-edge technology, but which looks very crude in hindsight.” DNA microarrays have since become one of the most important and widely used genomic tools for cancer research, allowing researchers to look for DNA changes by matching a particular specimen of tissue from a patient to features printed on the chip, which can be as high as tens of thousands or even millions, in one experiment.
“Oncogenomics is a marriage between molecular biology and genetics,” explained Dr. Wei. “Genomic studies systematically hunt for inherited genetic differences between people who have and those who do not have a specific disease. But do these differences cause the disease? Genomic studies only narrow the search to pursue that question.”
Drs. Khan, Wei, and their colleagues take the search further, trying to find out how DNA alterations of all sorts come to matter in cancer. “DNA is a very dynamic and complex system, subject to mutation every time cells divide,” Dr. Wei said. In the lab they are now sequencing the whole tumor genome using next-generation sequencing technologies and comparing the changes with those found in normal tissue taken from the same patient. The resulting molecular profiles, said Dr. Wei, are becoming a “game-changing way” to diagnose cancer, to predict a patient’s response to a particular therapy and his or her outcome, and even to personalize treatment for individual patients.
Their lab has been pioneering this approach since 2001, mastering and enhancing microarray technologies and creating new tools such as artificial neural networks—computer models that can adapt to input by changing and learning like the human brain. Their ultimate target is to discover the “drivers,” the critical genes that are causing cancers and which might also become targets for novel therapies.
From Bench to Bedside
Clinical relevance is the key. “You can go fishing for mutations associated with disease,” explained Dr. Wei, or “you can put a suspicious mutation into a cell and run a controlled experiment to see if it causes the disease.”
Those cell and animal experiments are Dr. Wei’s playing field. Reflecting back on the thousands of hours he has spent in the lab, honing his skills and his instincts as a molecular and cell biologist, Dr. Wei recalls the time he spent with his cousin Victoria studying at the University of Houston library until closing time, where he deciphered medical and biology textbooks and scientific papers with his newly acquired English—something Dr. Wei described as “not so much fun.” But the effort has no doubt helped him develop the sympathetic perspective to better supervise, train, and mentor postdocs in the lab.
The new generation of researchers will have to master a lot of new tools, while trying not to lose sight of what makes this kind of molecular science “biology”—the study of living things, he said.
“Picking up the newest technology, that’s not hard,” he explained. “The challenge is: How do you use this new technology in an innovative way? Everybody can learn to use tools, but how do you use the tools to make a beautiful piece of work?”
Dr. Wei is clearly driven by his lab’s mission. “These childhood diseases can be heartbreaking. Because many of them involve developmental genes, they form in a way that makes it impossible to screen and difficult to detect at early, treatable stages,” he explained. “By the time we get most of these kids into treatment, only 30 percent of them are likely to survive.”
You can hear the scientist explaining, but also an echo of a father who empathizes with the parents of children who have cancer. Dr. Wei paused, silent, before pointing with pride to an intricate 3-D collage his 7-year-old daughter, Esther, created that hangs on his office wall.
“The trick is to make your research into your artwork that would be beneficial to those kids with cancer,” he said.