Using DNA microarray technology to find the key to cancer

George Watts, PhD
George Watts, PhD

George Watts, PhD, has always been interested in how things work.

As a chemistry major at University of Delaware, George Watts, PhD, wasn’t content to be told a substance in the lab was toxic, he wanted to understand its actual effect on the body. That curiosity led him to study Pharmacology and Toxicology at the University of Arizona, during which time he did a rotation in an Arizona Cancer Center lab.

“It took me a week or two before I saw how cool molecular biology was and understood the size of the problem we were trying to tackle in terms of cancer, and I thought, ‘this is where it’s at.’ I’ve been here ever since,” he said.

As a postdoctoral fellow at the Arizona Cancer Center in 1997, Watts became the first scientist in the state of Arizona to analyze the genetics of cancer cells using DNA microarray technology.

A product of the Human Genome Project, DNA microarray technology has enabled scientists to use the human genetic code to study diseases at the most basic level with the aim of improved prediction, detection, monitoring and treatment.

Watts soon became the co-director of the Cancer Center’s Genomics Shared Service, which has provided the technological support for National Institutes of Health-sponsored research grants as varied as understanding gene-environment interactions in human disease to the development of molecular classifiers of leukemia.

In his personal research, Watts has used DNA microarray technology to discover epigenetic markers (changes in gene appearance or expression not caused by alterations in DNA structure) that can anticipate ovarian cancer disease course. Studies are now being done to translate these discoveries to clinical use.

Watts is currently using DNA microarray technology to try to determine factors related to cancer cell migration, invasion and angiogenesis (the development of blood vessels that support tumors). He’s now focusing on one gene, Fn14, which is expressed in certain types of cancer cells and seems to play a role in the process leading to metastasis.

“I think once you get the cancer started, Fn14 helps the tumor grow because it helps with angiogenesis and it increases the ability of the tumor cells to leave the site,” Watts said.

He’s working to determine whether inhibiting the function of Fn14 in tumor cells will stunt the cells’ ability to spread and grow a tumor at a new site.

“Our argument is: there’s a reason why cancer cells over-express this gene – it helps them do a number of things we consider bad - therefore this gene is a good target for therapeutic development,” Watts explained.

Fn14 seems to be an attractive target for the development of novel treatments for other reasons as well. It sits on the cell membrane and is a signaling receptor so new drugs wouldn’t have to be designed to go through the membrane, they just have to interact at the surface. Plus, an Fn14-targeted therapy could have wide-ranging applications.

“Fn14 is over expressed in esophageal cancer, lung cancers, breast cancer, glioma, and I have preliminary data that suggests it’s over expressed in colon cancer,” Watts said.

There is a lot more research that must be done before therapies based on his research can be developed or applied in a clinical setting, but Watts will continue working to deconstruct the base mechanisms of cancer, because understanding how cancer fundamentally works may be the key to preventing or curing it.