It’s personal. A pioneering Alzheimer’s researcher takes the helm of URI’s new George & Anne Ryan Institute for Neuroscience, ready to marshal the state’s burgeoning scientific forces into an organized army. Her mission: to battle the poorly understood causes of neurological decay that have touched so many lives—including hers.

BY TODD MCLEISH AND PIPPA JACK

The whole time that beta-amyloid research—into the protein that forms plaques in the brains of Alzheimer’s sufferers—has been grabbing all the headlines and research dollars, Paula Grammas has been quietly working on a different angle.

Actually, to say that Grammas does anything quietly isn’t quite right. She’s a petite New Yorker with a pronounced Far Rockaway accent who does not, to be clear, talk loudly—but who talks so confidently, concisely, candidly, and incredibly quickly, that it takes concentration to keep up. She commands attention. So no one would ever mistake her for a wallflower—or for her seamstress mother, who immigrated to the U.S. in the 1950s with Grammas’ father, both without a high school diploma, a penny or a word of English. “I wish I had one ounce of the courage my parents had,” Grammas reflects.

But then, it takes courage to keep working on an idea—that blood vessels play a role in neurodegenerative diseases like Alzheimer’s—when the rest of the research community is taking a different tack. It was something Grammas ran up against again and again in her early career. “I’d go to conferences where everyone was either presenting on amyloid or on tau, another abnormal protein. When I would get up to talk about vascular disorders, everyone would be like, ‘Sit down, little girl.’”

But that wasn’t Grammas’ style. An only child, she lost her father, who ran a diner in Long Island, to heart disease when he was only 55. Then, as Grammas was pursuing her Ph.D. in Detroit, it was suddenly clear that her mother, just back from a trip home to Greece to visit with her sister, would need to move in. Grammas had picked her up at the airport and been dismayed to discover she couldn’t walk. “When the neurologist put all the pieces together and realized she had ALS, I didn’t tell her right away,” Grammas remembers. “What was there to say? It’s just grim with grim. She became a prisoner in her own body.”

Grammas trained as an experimental pathologist, a field that allowed her to study in many disciplines despite the silos that ruled the academic world of the 1970s and 80s, when biochemists stuck to biochemistry, and cell biologists to physiology. Pathology integrated it all, an insight that is practically gospel in today’s research environment. But at the time, it gave Grammas an unusual edge, and she made full professor at 40. Since then, at universities in Michigan, Oklahoma and Texas, she has been an investigator for $24 million in research grants from the National Institutes of Health, published 141 peer-reviewed papers, won prestigious awards for her Alzheimer’s research as well as undergraduate teaching, and led neuroscience and aging centers.

But back when she took her first faculty position, her mother was just coming to live with her (she would hang on for only two more years, refusing a breathing machine to extend her life). Grammas was low woman on the totem pole at Wayne State, having to scale back on research to balance teaching responsibilities. But then, as now, she made adversity work for her. “They gave me the lectures nobody wanted: aging and nutrition,” she remembers. “I didn’t know anything about them, and I had to come up to speed. It was fate.” Indeed, those two areas ended up being a kind of prescription for her work since, a wide-ranging exploration into how blood vessels, inflammation, and diet play a role in Alzheimer’s, diabetes, AIDS and atherosclerosis.

There’s been no new treatment approved for Alzheimer’s since 2002 despite the millions the NIH has granted to amyloid and tau research. And all the treatments now available treat the symptoms only—they slow the synaptic communication deficits that occur early in the disease, but do nothing to halt the underlying decay of neurons. As Grammas points out, Alzheimer’s, like many diseases, seems increasingly likely to be caused by a confluence of factors, which makes it play out in different ways in different people. “It’s complicated,” she says, “which is why I would never presume to say Alzheimer’s, or anything else, is because of one thing. That’s also why it’s so important that everyone come together—and never dismiss a single lead.”

But research isn’t the only, or even the most important, factor in Grammas coming to URI. It’s an exciting time for brain research, here as everywhere, with Obama’s brain mapping project announced in 2013 and brain imaging technology growing by leaps and bounds. The fact that URI brought its neuroscience programs together under one multidisciplinary umbrella in 2011 is a plus; so is its push to hire more faculty. But Grammas, with her personal sense of urgency and hard-won skepticism of accepted wisdom, says what really attracted her was the collaborative atmosphere at URI and across the state. “Between Lifespan, Care New England, Brown University and the VA—to have so many entities play nice is unheard of,” she says. “My take on this is, I don’t want us to reinvent the wheel or compete in areas where other institutions in the state already have expertise. We can do this together.”

She is grateful for the leadership of donors like former CVS Health chair Thomas M. Ryan ’75 and his wife Cathy, who gave URI $15 million to establish The George & Anne Ryan Institute for Neuroscience, which will focus its research, teaching and outreach on neurodegenerative disorders. It’s personal for the Ryans, too—the institute memorializes Tom’s father, who died in 2004 from a stroke and resulting Alzheimer’s, and his late mother, whose health declined while caring for her husband.

Ryan says he’s looking forward to seeing Grammas in action. “Her demonstrated ability to collaborate across multiple organizations and bring in a variety of perspectives is critical,” he reflects. “I believe we will position Rhode Island as a primary destination for research, therapies and treatments.”

Grammas acknowledges that expectations are high, but seems anything but daunted—except, perhaps, at the prospect of once more enduring Northeast winters after years in Texas. But when it comes to the Institute, she’s ready. “Neuroscience is probably the area of biology that we know least about, so there’s the most potential for groundbreaking discoveries,” Grammas says. “Where we were with the cardiovascular system in the 1960s, is where we’re at with the nervous system now. And think about how far we’ve come.” •