Berkeley cell biologist wins Lasker Award

By Robert Sanders, Public Affairs

25 September 2002 | Many high-school students dread science-fair projects, but Randy Schekman lived for them, a hint of the passion that would drive his research for 30 years and earn him the nation’s highest award for basic medical research, the Lasker Award.

Schekman, 53, a Berkeley professor of molecular and cell biology and an investigator with the Howard Hughes Medical Insti-tute, will share the 2002 Lasker Award for Basic Medical Research with James Rothman of the Sloan-Kettering Institute in New York City.

The Lasker Awards for basic and clinical research are touted as the American equivalent of the Nobel Prizes, and 65 Lasker Award recipients have gone on to win Nobel prizes. Schekman is being honored for his pioneering work to describe the secretion system of cells, a biological system that is critical in the treatment of some forms of diabetes, hemophilia and, possibly, Alzheimer’s disease.

He and Rothman will receive their awards during a luncheon ceremony Sept. 27 at the Pierre Hotel in New York City.

The two scientists, working independently, have mapped out one of the human body’s most important transportation systems. All cells have a specific way of secreting hormones and enzymes, and adding to their surface, which allows them to grow and divide. That secretion system uses little membrane bubbles to move molecules around inside the cell, but it is so crucial to cell growth and division that any snags along the way will inevitably lead to the cell’s death.
“Ten percent of the proteins that cells make are secreted, including growth factors and hormones, neurotransmitters by nerve cells, and insulin from pancreas cells,” Schekman says.

The discovery has important implications for some diseases, such as Alzheimer’s. Recent findings hint that some Alzheimer’s patients may have a problem with this secretion pathway. Their cells seem unable to package up certain proteins for transport to the cells’ surface; hence, the cells, unable to secret the proteins, become overloaded until they die.

A rare form of hemophilia — factor-5, factor-8 deficiency — may also result from a defect in the packaging machinery of cells. Patients with this form of the disease have low levels of two different clotting factors. In 70 percent of the patients, the clotting-factor membrane receptor is defective and interferes with the secretion of the two clotting factors. With blood that does not clot, patients with that form of hemophilia face potentially life-threatening situations every time they cut a finger.

Schekman got his start in the study of cell secretion at Stanford University, which was a hotbed of molecular biology research in the early 1970s. Working as a graduate student in the lab of renowned biochemist Arthur Kornberg, he assisted with cutting-edge DNA replication experiments. “The ferment in that department was unbelievable — for DNA work, it was the center of the universe,” he says.

While Schekman was purifying enzymes involved in chromosome replication, Stanford colleague Stanley Cohen teamed up with UC San Francisco professor Herbert Boyer to insert recombinant DNA into bacteria that could be cloned. That discovery launched both the genetic-engineering revolution and the first company to exploit the technology to make pharmaceuticals, Genentech.

“I learned a great deal, not just about biochemistry or DNA, but about how to look at a problem, how to take it apart and put it back together, how to focus on things,” Schekman says. “It really set the stage for me. Focus, in particular, was critical to my work, and I learned that from Kornberg.”

But the atmosphere in Kornberg’s lab was highly competitive and the field of DNA replication contentious. So Schekman found a less-competitive niche at UC San Diego, where he spent two postdoctoral years with John Singer studying cell membranes. Singer was doing groundbreaking work with electron microscopy to study the membranes of mammal cells, but Schekman was frustrated by the lack of tools to manipulate these cells. Spoiled by the well-equipped laboratories he used to work in, he decided to focus on another easy-to-grow microbe, baker’s yeast, in the hope that combining genetics and biochemistry would lead to an understanding of the machinery of cell secretion.

He left UC San Diego for a position as assistant professor of biochemistry at Berkeley in 1976, and continued his studies of yeast genetics. In the ensuing years, Schekman was able to unravel the machinery by which yeast cells sort, package, and deliver proteins via membrane bubbles to a cell’s surface, where they are secreted. He learned that cells also use this process to control other activities, such as the intake of nutrients, like glucose, which proved important in the treatment of some forms of diabetes.

In the 1980s and 1990s, these findings enabled the biotechnology industry to exploit the secretion system in yeast to create synthetic and industrial enzymes. Today, one-quarter of the insulin used by diabetics worldwide is produced and secreted by yeast, and all of the hepatitis B vaccine is produced by yeast. Both systems were developed by Chiron Corp. of Emeryville, during the 20 years in which Schekman served as a company consultant.

“Our findings have aided people in understanding these diseases,” says Schekman, whose once-isolated research niche is now crowded. Fortunately, although he has little time to pursue all of the new research directions his work introduced, his graduate students are picking up the slack.

But, he admits, his children won’t be following the same path. Both are musically inclined, which reflects the interest in classical music and opera shared by Schekman and his wife, Nancy Walls. Son Joel is a graduate student at the University of Southern California, a classical musician studying clarinet. Schekman’s daughter, Lauren, is a junior at Berkeley, majoring in economics.

“The highlight of my 27 years [at Berkeley] was when she was admitted as a student,” says the “dad” in him. “Even more so, when I had the opportunity as a proud father to tour the campus with her on Cal Day 2000, I was in seventh heaven.”