Couple joins forces to research breast cancer genetics

If one sign of a happy relationship is that the partners rarely run out of things to talk about, then cancer researchers Stephen Baylin and Feyruz Rassool of Baltimore have been a blessed couple indeed.

In the 13 years they've been married, they've shared their passions for everything from hiking to Muddy Waters to Asian art. They regularly swap tales of their latest triumphs in the lab or struggles with a grant proposal.


"We're better than the sum of our parts," Baylin said.

Now, women struggling with breast cancer might benefit from the way the pair interact.


Last October, Baylin, deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, and Rassool, an associate professor at the University of Maryland Marlene and Stewart Greenebaum Cancer Center in Baltimore, jointly won the inaugural Laura Ziskin Prize in Translational Cancer Research.

The $250,000 grant, named for Laura Ziskin, a Hollywood film producer who died of metastatic breast cancer two years ago, is given annually to a research team investigating radical new cures for the disease that kills tens of thousands of American women each year. It was the first time the two have united on a project.

Baylin and Rassool haven't cured the malady in their 12 months of work, but they've made inroads, using their separate strengths to develop a one-two chemical punch that kills its malignant cells with surprising speed.

"We're already using certain drugs, known as PARP inhibitors, to fight [breast and other] cancers, and what Steve and Fey have shown is that those drugs may work a lot better if the patient receives some epigenetic therapy first," said Dr. John Glaspy, a professor at UCLA's Jonsson Comprehensive Cancer Center who treated Ziskin and has followed their work. "It's a finding with major implications."

Oncological jargon aside, Baylin, 70, and Rassool, 53, call to mind discrete materials that spark a reaction when mixed in a beaker. They differ, but they have chemistry.

Baylin was born in North Carolina, where his father was a radiology professor at Duke. He washed test tubes in the old man's lab, grew up with a taste for research and went to medical school in hopes of becoming a physician.

But the causes behind disease intrigued him more than treating patients. He joined the oncology and medicine departments at Johns Hopkins and researched cell biology and the genetics of cancer.

"I just morphed into this other side, into science," Baylin said. "I couldn't leave it alone."


Rassool, whose ancestry is Indian and Lebanese, began life in South Africa, where her father, a high school English teacher, fought against apartheid. The family fled the country for London for political reasons.

Rassool excelled at English literature and writing, and planned to become a Shakespearean actress. But she couldn't stop thinking about the complex possibilities of genetics, a subject she took on in high school and college.

"I was fascinated by the question of why genes changed, by what makes certain genes, when altered, cause cancer," she said.

She applied to graduate programs in the sciences, earned a doctorate in biology and landed a fellowship with Janet Rowley, a University of Chicago geneticist famed for showing that two normal genes can collide and form another — and that this process, known as chromosomal translocation, is one cause of leukemia.

Rassool was drawn to investigating DNA, the tiny molecular strands that encode a living organism's genetic information, especially the question of how it triggers cancer if damaged by external agents like radiation or smoking. Her research has centered on using our increasingly elaborate knowledge of genetics to disable those processes.

Baylin, on the other hand, became less interested in the DNA itself than in the physical materials (mostly proteins) that surround it. During the 1980s, he helped establish that if DNA is life's raw material — its computer hardware, if you will — then those packaging materials, known as the epigenome, are its software, allowing the organism to create distinct identifiable parts such as eyes, toes and kidneys.


Over the years, Baylin established himself as a pioneer in the now-burgeoning field of epigenetics, showing it's not just flaws in DNA strands that lead to cancer. Abnormalities in the packaging materials, or epigenome, also are present in most types of cancer and may even cause it — and treating a damaged epigenome can even reverse flaws inside the DNA.

Looking back, it seems almost evitable that when hardware expert Rassool and software maven Baylin met at a conference in China, they'd connect. They fell to talking science, then wandered with equal vigor into Bach, baseball and Woody Allen. They met several times on three continents over the next two years, married in 2000 and haven't stopped gabbing since.

They share a Federal Hill rowhouse and work a few minutes apart, Baylin at the Bunting Blaustein Cancer Research Building on Orleans Street and Rassool in her labs on South Greene Street. They try to coordinate their busy schedules, often Skyping midday. And over the years, as they chatted, a question kept arising: If cancer can be attacked both genetically and epigentically, what would happen if you tried both approaches at once? The Ziskin Prize offered them a chance to find out.

Ziskin, a Hollywood powerhouse who helmed hits such as "Pretty Woman" and all three "Spider-Man" films, was in the midst of a battle with breast cancer in 2008 when she and eight other women in show business founded Stand Up 2 Cancer, a nonprofit aimed at accelerating ground-breaking research in cancers. (Baylin, co-recipient of an early Stand Up 2 Cencer grant in his field, spoke admiringly of her courage.)

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When Ziskin died at 61 in 2011, she earmarked $1.1 million to set up the annual grant on breast cancer research. The couple proposed a dual treatment, hitting tumors first with Vidaza, an epigenetic drug, then with ABT-888, a so-called PARP inhibitor that affects the DNA side. Their idea was chosen during Breast Cancer Awareness Month 2012.

They got results. The paired drugs killed so many more breast cancer cells (and some leukemia cells) than they would have if used separately that Baylin, no stranger to breakthroughs, called it a "Eureka" moment. The University of Maryland prepared to begin clinical trials. But at about the same time, a California pharmaceuticals company, BioMarin, developed a PARP inhibitor, BMN-673, so powerful it worked better than their joint approach.


That hasn't deterred the duo. Science works in fits and starts, they say, and any advance against cancer is great news. And their work showed that software and hardware almost certainly work together in cancers, including breast cancer, a finding likely to spark further discoveries.

They still have half the Ziskin grant money left and plan to spend part of the next year experimenting with dosage sizes and other variables. They'll be returning to their numerous other cancer projects as well. Both hope future collaborations are in the cards.

In the meantime, the conversation continues. Baylin and Rassool can be seen most weekends chatting as they hike through the Inner Harbor or over tapas after a film at the Charles. He's learning blues guitar, and she lends vocals. And science — they never tire of that subject.

"It may strike other people as strange," Baylin said, "but for us, it's a language of romance."