Science With Heart

Can a compound in red wine improve heart healing?

In modern times, the health benefits of drinking wine (in moderation) continue to be extolled. Most often, drinking wine is associated with improving cardiovascular health—and the key compound at the root of this claim is frequently resveratrol.

Resveratrol is a molecule found not only in red wine but also in berries, chocolate, peanuts, and a host of other plant-based foods. If resveratrol sounds familiar, it may be because it was briefly a media darling. Beginning in the late 1990s, a handful of studies suggested that, thanks to resveratrol, red wine might slow aging and inhibit cancer.

Not surprisingly, the idea of drinking red wine and eating chocolate to live longer, disease-free lives captured the imagination. The media couldn’t resist. Countless stories appeared with variations of this headline, which ran in the New York Times in 2003: “Life- Extending Chemical Is Found in Certain Red Wines.”

A decade later, about the time Casey Jones, assistant professor of chemistry, was hired by Lewis & Clark, it became clear that people couldn’t really sip and nibble their way to longevity. Subsequent studies—“large, long-term studies,” says Jones—confirmed that there is no statistical benefit to consuming a diet high in the supposed miracle molecule.

The problem is not with the molecule itself, which still seems to hold much promise, but rather in its delivery; that is, you could never consume enough of it to have the desired impact. In 2008, The New York Times reported (without apparent irony) on the possible health benefits that came with giving mice a resveratrol dose equivalent to 35 bottles of red wine a day, an excessive amount for even the most committed oenophile.

Jones, however, believes that resveratrol may yet have a second act. Along with a committed team of Lewis & Clark students, she is interested in using the compound to help make better biomedical devices—specifically, arterial stents. These wire mesh tubes are used to fight coronary artery disease, the leading cause of death for adults in the United States.

Melding Biology and Chemistry

Casey Jones, a stellar teacher who earns raves from past and present students, arrived at Lewis & Clark by way of Reed College, the California Institute of Technology, Princeton University, and Oregon Health & Science University.

Jones attended Reed College from 2001 to 2005, developing a love for both Portland and organic chemistry, thanks to two professors. She conducted undergraduate research with Pat McDougal and also met Maggie Geselbracht, an inspiration for her future in undergraduate teaching and research. In 2005, Jones began her doctoral studies at Caltech in the lab of David MacMillan, where she synthesized amino acids not found in nature. When MacMillan moved to Princeton in 2006, Jones left her native California and went along.

The biology side of chemistry was really pulling me in. I was getting the sense that, beyond just doing something really cool scientifically, chemistry and biology could work hand in hand to make something that is relevant and valuable for society.Casey JonesAssistant Professor of Chemistry

Once at Princeton, Jones finished her PhD in the lab of Jeffrey Schwartz, who studies chemistry involved at the interfaces between dissimilar materials like metals, plastics, or synthetic materials (on the one hand) and living tissue (on the other). Understanding what happens at these interfaces is key to improving biomedical devices, which often result in tissue damage or infection when implanted.

Jones became engrossed by the effort to grow cells on metal and polymer surfaces. Her description of those years brings to mind learning how to plan and tend a garden, albeit on a micro scale. If the surfaces were prepared and treated just right, the cells could be made to grow and flourish in specific shapes and patterns.

“The biology side of chemistry was really pulling me in,” Jones says. “I was getting the sense that, beyond just doing something really cool scientifically, chemistry and biology could work hand in hand to make something that is relevant and valuable for society.”

After Princeton, Jones landed a prestigious National Institutes of Health postdoctoral fellowship at OHSU. There she worked in a lab exploring how to improve cardiovascular devices, a line of inquiry she’s continuing at Lewis & Clark.

Helping the Body Heal

When Jones arrived at the college in 2013, she knew her lab work would combine her background in chemically gluing organic molecules to synthetic surfaces and her fascination with endothelial cells. According to Jones, endothelial cells line the inner walls of blood vessels “and form a layer that separates our bodies from our blood.” She adds, “Together, endothelial cells form a huge organ, which is like the skin. But since it’s on the inside, we usually don’t think of it.”

Though out of sight, the health of this organ, the endothelium, is in fact hugely important. These cells collectively act as a gatekeeper, either pulling nutrients into tissues from the blood or keeping toxins out of the body.

Damage to the endothelial cell layer is one of the causes of coronary artery disease. “We need to figure out a way to help that layer,” says Jones. When stents are implanted, they can activate the body’s injury response, leading to blood clots and other problems. Jones thinks that coating stents with a resveratrol-releasing layer might help promote endothelial healing.

“My goal in setting up my lab was to have students be able to synthesize different versions of resveratrol molecules, test them with endothelial cells grown in culture, and see how the cells respond,” says Jones.

To do this, Jones needed two things: the right organic molecule, one that’s fairly easy to make in the lab and that might promote health and growth of endothelial cells, and the right collection of students. As it turns out, she found both.

A Promising Molecule + Talented Students

Despite resveratrol’s travails in the press and academic literature, there is much to recommend the molecule. It’s fairly easy to assemble resveratrol and several closely related cousins, or analogues, in an undergraduate lab. The molecule also includes several hydroxyl groups, which are oxygen and hydrogen atoms tightly bound together. These groups make for good handles when attaching resveratrol to a treated metal surface via the process Jones learned at Princeton.

Evidence is mounting that resveratrol, delivered in sufficient amounts to areas of the body that might most benefit—for example, an artery recovering from the insertion of an arterial stent—activates proteins known as sirtuins. The scientific consensus seems to be that these proteins are associated with many downstream health benefits, including scavenging free radicals, decreasing inflammation, and helping endothelial cells heal.

“The overall concept that resveratrol is a miracle cure came and went,” Jones said. “But I think targeted applications will come out of the work to discover the mechanisms sirtuins help to trigger.”

In other words, Jones and her students may be helping to write resveratrol’s redemption story.

One of those students was Mackenzie Batali, who graduated in May 2015 as a chemistry major. Batali’s work culminated in a nearly 80-page thesis that dispels any doubts that undergraduates can do original research at a high level. More important, her thesis points the way to which versions of resveratrol might show the greatest promise for use with stents.

Working with Casey has been a great experience. When I first went into her lab, I felt like a student; now I feel like a scientist. Casey taught me how to ask the right questions and how to follow my scientific intuition.Julian Harris CAS ’16

Batali’s work earned accolades beyond Lewis & Clark. She presented at various conferences, most notably the well-attended American Chemical Society’s national meeting in San Francisco in fall 2014. As Batali and her lab mate, then-junior Julian Harris, fielded questions about the poster summarizing their work, “lots of people came up and were surprised they weren’t graduate students,” says Jones.

“Casey is an incredible mentor,” says Batali in a phone interview on her lunch break from her new job as an R&D technician at Emerald Performance Materials in Kalama, Washington. “I never left a meeting feeling stressed or discouraged. I would come to her when I was struggling, and I would always leave her office or the lab feeling 10 times better than I thought would be possible.”

“Working with Casey has been a great experience,” says Harris. “When I first went into her lab, I felt like a student; now I feel like a scientist. Casey taught me how to ask the right questions and how to follow my scientific intuition.”

Strong Bonds

This past summer, four students joined Jones in her lab: senior Julian Harris, senior Jacob Gigliotti, junior Naomi Widstrom, and sophomore Will Owen. All of them worked in Jones’ lab with support from the John S. Rogers Science Research Program.

John S. Rogers Science Research Program

This past summer, 55 Lewis & Clark students—including the students in Casey Jones’ lab—took part in the John S. Rogers Science Research Program. This initiative is supported, in part, by the James F. and Marion L. Miller Foundation and works in partnership with Lewis & Clark’s Howard Hughes Medical Institute Undergraduate Science Education Program.

The Rogers program promotes collaborative research in the mathematical and natural sciences by providing the framework and financing for more than two dozen student-faculty projects each summer. It gives science majors a taste of real-world scientific investigation and helps them acquire skills they need to further their education and pursue a career in the sciences.

“Rogers fellows are treated as fledgling scientists who have a responsibility to communicate the purpose and results of their work to a general audience,” says Michael Broide, associate professor of physics and director of the program. “And when they go to graduate school,” he adds, “they hit the ground running.” More

During a typical lab session in late July, Harris and Owen huddle in front of a computer screen, studying a Tinkertoy-type 3-D model of a sirtuin protein. In the fume hood at the back of the room, a darkish liquid burbles away. It’s another resveratrol variation (or analogue) to try out with the lab’s cultured endothelial cells, a task that Gigliotti and Widstrom will likely complete.

Harris dons gloves and safety goggles to extract a small piece of metal (called a coupon), half the size of a postage stamp. Jones and her students will use a process to make the coupon chemically sticky—think licking a stamp before putting it on an envelope—and attach the resveratrol analogue. The coated coupon will then be placed in dishes of endothelial cells, which, with any luck, will start proliferating and growing faster, thanks to the molecule.

Jones asks for an update and Owen announces that the liquid in the hood “sort of looks like teriyaki sauce, but maybe that’s just because I’m hungry,” before a more serious discussion of whether the synthesis was on track. (It was.)

Indeed, food is one of the ways Jones keeps the mood light in her lab. Earlier in the summer, her group celebrated National Corn on the Cob Day. (June 11, if you want to mark your calendars for next year.) Birthdays are marked with unique homemade dishes that could only be dreamed up by creative chemists living in a foodie city like Portland. The main dish at the most recent celebration: falafel waffles. During the 2015–16 academic year, Jones is launching a molecular gastronomy club. Once a month, club members will prepare a unique dish and talk about the science going on behind mixing the ingredients and doing the cooking. “A fun new adventure,” Jones calls it.

Stories shared by Jones and her students suggest that shared adventures beyond the lab cement the relationships, much like the strong chemical bonds that tie resveratrol to the tiny metal squares churned out by her lab.

Looking Forward

Casey Jones has plans for at least a decade’s worth of experiments on resveratrol. Lewis & Clark, she says, is just the right place to explore whether the molecule might yet live up to its promise.

“Occasionally, it’s hard to get grants funded for this project. I’ve gotten comments from reviewers that there’s no way undergraduates can do all these things,” says Jones, with a wry smile and a glint in her eye.

“But our undergraduates can do amazing things,” she says, knowing that her retort to detractors is based on what science prizes most of all: “I have proof!”

Geoff Koch is a writer in Portland. His last article for the Chronicle, “Tamily Weissman-Unni and the Amazing Technicolor Brain,” appeared in the winter 2013 issue.