You never know what sort of wonders will emerge from the laboratory of Kit Lam. In addition to being chief of the Division of Hematology and Oncology at UC Davis Cancer Center, Lam is also a combinatorial chemist, plowing the outermost edges of the burgeoning field of biotechnology in an effort to develop novel cancer treatments.
Combinatorial chemistry involves the rapid synthesis and screening of large numbers of different but related chemical compounds. Lam's particular mission is to develop and arm peptides to hunt down and kill targeted cancer cells without destroying their healthy neighbors. He holds Ph.D. and medical degrees, blending clinical expertise with a knack for basic research that is described as nothing short of exceptional by colleagues.
Before arriving at UC Davis in 1999, Lam was an associate professor of medicine, microbiology and immunology at the Arizona Cancer Center at the University of Arizona. It was there, in 1991, that he created a chemical library containing more than one million different peptides – the short stretches of proteins responsible for the work of a cell. Each peptide was housed on a different plastic bead with a diameter similar to that of a human hair. The beads allowed laboratory scientists to run millions of chemical reactions simultaneously, a huge time-saver in the hunt for more effective and less toxic cancer drugs.
Recently, Lam added another important tool to the combinatorial chemist's research kit. In an April article published in the Journal of Combinatorial Chemistry, Lam revealed a new technique that involves color-coding those polystyrene beads, creating an array he calls "rainbow beads."
To create this kaleidoscope, Lam stained the beads with oil-based organic dyes that function as a sort of color-coded labeling system. The dyes, trapped inside the bead, do not affect cell binding to the bead's surface and are insoluble in water.
Simple, but powerful
Seemingly simple, the method substantially accelerates screening because the color-coding allows for small samples from multiple chemical libraries to be simultaneously screened against live cells "in one pot." This, Lam says, allows the binding of cells to these different libraries to be compared directly.
Another major advantage is that scientists need only an ordinary inverted microscope to conduct the analysis, as opposed to a more sophisticated – and expensive – fluorescent microscope or flow cytometer.
The technique also allows researchers to color-code beads displaying known cancer-targeting molecules.
"If I take cancer cells from a patient named John and put them in a dish with 10 different colored beads, I can look and see which bead the cancer cells bind to," Lam says. "Each bead has a different chemical molecule, so immediately I can make a diagnostic connection about John's cancer, and maybe even use the specific molecule as a vehicle to deliver drugs to John's cancer while sparing his normal cells. And, instead of doing 10 separate experiments to get this information, I can do this in just one."
Lam's work is part of broad revolution that is radically changing cancer research and how drugs are developed. Traditionally, oncologists have drawn on natural materials to create cancer drugs that are nonspecific and often carry significant side effects for patients.
But, using sophisticated chemistry, scientists have increased their understanding of the molecular biology of cancer and are creating millions of new compounds in the laboratory. This paves the way for the development of drugs that can target cancer cells more precisely and effectively.
Leading the way toward individualized treatment
For now, Lam says, the rainbow beads are mostly useful in the laboratory. Ultimately, however, he hopes the system might be used as a bedside diagnostic test, a sort of "dip stick," he said, that could yield quick results and help cancer specialists provide individualized patient therapy.
"Many of Dr. Lam's inventions have been used extensively by cancer scientists," says Chong-xian Pan, assistant professor of hematology and oncology. "My work has benefited tremendously from his findings. His rainbow bead-coding system, for instance, has greatly accelerated the process of identifying bladder cancer-specific cells that can now be targeted for new treatments."
Lam received his bachelor's degree from the University of Texas at Austin, his Ph.D. from the University of Wisconsin and his medical degree from Stanford University. His interest in cancer took root when he was a graduate student at the McArdle Laboratory for Cancer Research at the University of Wisconsin. It intensified later, when he was at Stanford, after his father contracted lymphoma and ultimately died from the disease.
Last year, he and four other researchers developed an efficient, high-yield method for the synthesis of flavonoids, cancer-fighting molecules that occur naturally in fruits and vegetables. That work, outlined in a January 2007 article in the Journal of Combinatorial Chemistry, comes at a time of increasing interest in the design of synthetic anticancer compounds that mimic natural products and can be less toxic than current medications.
In addition to cancer-drug development, Lam is also interested in signal transduction, molecular immunology, chemical microarray, proteomics and Alzheimer's disease. He combines his passion for research with valuable clinical experience, a winning combination that brought him to the attention of UC Davis Cancer Center in the late 1990s, in particular the chair of internal medicine – Fred Meyers – who recruited Lam.
"Dr. Lam is unique in the fierce intelligence and commitment he brings to his work," says Meyers. "I have met many oncologists and investigators during my career. He is one of a handful who I believe will cure a cancer during my lifetime."