Protein research by University prof may unlock new cancer treatments

A team of molecular biologists at the University, led by associate professor Yigong Shi, and the U.S. Department of Energy's Brookhaven National Laboratory have unveiled details about the structure of the cancer-inducing protein Ski.

Ski is a protein that is naturally found in the body. When mutated, it interferes with the mechanisms of cell growth, causing cancer in the individual.

"Ski is a protein that performs several other functions in the body," Shi said. "What our lab is interested in finding out is how it promotes cancer growth."

Cancers gain their advantage by the disruption of cellular signals, he said. Shi and the Brookhaven team aim to discover how the cancer-causing protein Ski disrupts the pathway that affects cellular growth.

During the past year, the Princeton team has concentrated on the structure of the Ski protein using X-ray crystallography — a method by which the three-dimensional structure of the protein can be determined using X-rays.

...Determining the 3-D structure of Ski will help researchers decipher where certain atoms are located in the protein and how each atom relates to the protein's function.

"We have a motto in our lab," Shi said. "Crystal structure makes things crystal clear!"

Using the information about the crystal structure, researchers can induce mutations in the protein to determine how such mutations will affect the function of the protein.

Support nonprofit student journalism. Donate to the ‘Prince’. Donate now »

Knowing the structure of the Ski protein will also help pharmaceutical companies develop drugs that could inhibit Ski's cancer-inducing properties.

"It would be great to one day see my work used in the creation of medications to help cancer patients," Shi said. "The goal is to have the work done here translated into the clinical field."

Several pharmaceutical companies have already shown interest in Shi's old work and are planning to use the structural information to develop drugs that may help fight cancer, he said.

Though the human genome has been sequenced for years, little is known about most disease-causing proteins. Most of the information available today has been discovered in the past two to three years. Much of this work has concentrated on genetic factors, cellular pathways and the interaction of proteins.

Get the best of the ‘Prince’ delivered straight to your inbox. Subscribe now »

"I consider myself a structural biologist more than a molecular biologist," Shi said. "My lab spends most of its time on determining the structure of disease proteins to help understand their function."

Shi first came to the United States in 1990 after obtaining his undergraduate degree in Beijing, China. He then obtained a doctorate from Johns Hopkins University and a postdoctoral degree from the Memorial Sloan Kettering Cancer Center in New York. Shi came to the University as a researcher in February 1998, working in the Schultz Laboratory of the molecular biology department.