Alumni Profiles

A Microscopic Magic Bullet
John Rossi '69 seeks cures for AIDs and cancer at the molecular level



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In a city known for its movie stars, you'd hardly expect a hospital lab to be where the action is.

But in a research lab at the City of Hope Hospital in Los Angeles' Duarte suburb, John Rossi '69 and his team of 20 scientists are making discoveries with the potential to change the lives of millions. By manipulating molecules and controlling the expression of certain genes, Rossi and his researchers are at the forefront of discoveries that may some day cure two of medicine's most dreaded illnesses: cancer and AIDS.

Thanks to newer medications that hold the human immunovirus at bay, over the past decade AIDS has gone from being regarded as an imminent death sentence to a treatable illness. "While of course that's good news, the downside is that a lot of people have stopped paying attention," Rossi says. "And the fact is, AIDS is still a lethal epidemic." The drugs that are effective against the virus cannot be tolerated by some patients and are extremely toxic and debilitating in others. In all patients, they work only to suppress, not eradicate, HIV. "Even the healthiest patient who stops treatment will experience a full-force return of the virus within days," Rossi explains. "For me, it remains essential that we continue to pursue a cure for AIDS."

Rossi's descriptions of his work are peppered with references to aptamers, nanoparticles, ribozymes and RNA catalysis—the building blocks of biological therapies that manipulate genes to halt or reverse the damage done by disease. One application modifies genes known as small interfering RNAs to silence certain genetic messages. For patients with AIDS, small interfering RNAs disrupt the growth and replication of HIV. For patients with cancer, these genes hold the potential to destroy cancer stem cells that have eluded chemotherapy. A second therapy Rossi has developed utilizes different RNAs known as ribozymes to target HIV-infected cells. While much of Rossi's work is strictly lab-based, this particular application is currently being tested with 10 HIV-positive patients—an exciting step that signals the therapy's promise.

Raised in Connecticut, Rossi followed in the footsteps of his father, Louis '38, and enrolled at UNH, planning to study forestry. A genetics class convinced him to switch to biology, and after graduation he moved with his wife, Mary Jane Robert Rossi '71, to UConn, where he earned a Ph.D. in genetics. In 1980, he landed a position at City of Hope, where the nascent field of AIDS research was getting its start.

Today, Rossi serves as chair and professor of molecular biology and dean of the City of Hope's Irell and Manella Graduate School of Biological Sciences. He has been recognized with many awards, including the Cozzarelli Prize from the National Academy of Sciences, an honor he's quick to point out he shared with one of his graduate students. Despite 80-plus-hour workweeks at an age when many are thinking about retirement, Rossi says his work is fun. For him, the excitement lies not in personal achievement but in drawing ever closer to that elusive goal: a cure.

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