Defending His Dissertation

Andrew Fontanella could be forgiven for wanting to be somewhere else. At six foot three, with a tousle of curly dark-brown hair that adds another inch or two, he looms above everyone else in this cramped second-floor classroom in the generically named Medical Sciences Research Building on Research Drive. It’s 11:30 on a windy Wednesday morning in March, and Fontanella keeps an eye on the clock. It ticks closer to the noon hour, when he will face a group of esteemed Duke faculty members to defend his doctoral dissertation.

Fellow graduate students and members of his biomedical engineering research lab file in to the classroom and grab deli sandwiches from a selection provided by local restaurant Saladelia. For dessert, there are two homemade cheesecakes, baked by Fontanella’s mother, Evelyn. She and Andrew’s father, Bill, spent nine hours on the road yesterday, driving from Scranton, Pennsylvania, through a late winter snowstorm to be here for the culmination of their son’s graduate-school career.

It’s a journey that began in the fall of 2005, when twenty-three-year-old Fontanella arrived at Duke with a bachelor’s degree in electrical engineering from Penn State. A few years into his graduate studies, in optical imaging and spectroscopy, he began to realize that the work was more abstract than he’d envisioned. Biomedical engineering, with its interdisciplinary approach to devising practical applications for clinical settings, seemed a better fit. He contacted Mark Dewhirst, the Gustavo S. Montana Professor of radiation oncology and director of the Duke Comprehensive Cancer Center’s radiation oncology program, who agreed to serve as his adviser.

“Meeting cancer patients gave me a really valuable perspective on why researchers do the work they do.”

And so, for the past six years, Fontanella has been conducting research in Duke’s Tumor Microcirculation Lab, examining the vasculature of tumors and how it reacts to different forms of radiation therapy. In addition to long hours spent in the lab, Fontanella worked directly with oncology physicians, nurses, and patients to analyze how blood flow to a tumor is altered by hyperthermia therapy. (Hyperthermia treatment involves applying heat to the tumor to increase blood flow and enhance the efficacy of radiation.) As the nurse or doctor placed an optical fiber probe on the patient’s tumor, Fontanella managed the software that collected data, and he engaged in conversation with the patient.

“Meeting cancer patients gave me a really valuable perspective on why researchers do the work they do,” says Fontanella. “People were so willing to enroll in [cancer] studies that wouldn’t help them directly, but that might help the next person.” This past September, his research took on a deeper personal dimension when his maternal aunt, Roberta Ritter, died at the age of fifty-seven, a year after being diagnosed with stomach cancer. He has dedicated his dissertation to her.

As the noon hour approaches, the group files out of the classroom and snakes its way across an elevated walkway into the adjoining Clinical and Research Laboratory and another nondescript classroom. Fellow biomedical engineering doctoral student Amy Frees sets up the laptop on which Fontanella’s PowerPoint presentation is loaded while he stands at the lectern placed at the front of the room. Dewhirst is joined by the other members of the dissertation committee: biomedical engineering professors Nimmi Ramanujam and Joseph Izatt; medical oncology professor Victoria Seewaldt, director of the Breast Cancer Prevention Program at Duke’s Women’s Wellness Clinic; and associate professor of surgery Bruce Klitzman, who also holds appointments in biomedical engineering and cell biology.

“It is a privilege and an honor to introduce Andrew Fontanella to you,” Dewhirst says, welcoming the assembled group. “When I first met Andrew, he knew a lot about electrical engineering but not that much about biology. When I suggested that he look into angiogenesis”—the growth of new blood vessels from existing vessels—“he said, ‘What’s angiogenesis?’” Everyone in the room laughs.

After concluding his remarks, Dewhirst takes his seat, and all eyes are on Fontanella, whose quiet composure of half an hour earlier has given way to understandable nervousness. He faces the audience members without looking directly at anyone, hoping not to stumble over his words. Although he turned in his dissertation a week earlier and has run through the presentation over and over again, this time is different. It’s the real deal.

Fontanella takes a breath and launches his presentation. The title of his dissertation appears on the screen: “Novel Image Processing Techniques to Assess Radiation Responses in the Tumor Microenvironment.” Throughout his talk, he uses the first-person plural as he elaborates on his doctoral research.

“Our results indicate that the tumor vasculature may be sensitive to widefield tumor irradiation, but after spatially fractionated dosing, a robust angiogenic response is observed that may be associated with indirect radiation response in the spared tumor fraction—a phenomenon known as the radiation bystander effect,” he explains. “This response may be modifying the regulation of certain cellular signaling pathways associated with angiogenesis, tumor cell proliferation, invasion, and metastasis.”

For those whose recollection of highschool science is hazy, Fontanella’s investigation explores an intriguing and innovative approach to cancer treatment in which radiation is delivered in a non-uniform manner. Traditional modes of radiotherapy typically strive to deliver constant doses across the tumor, with the goal of sparing any normal cells that lie outside the tumor itself. The rationale for this conventional approach considers only the direct killing of the proliferating cancer cells. But he and other researchers have been exploring alternative radiation models that instead target the vascular component by delivering non-uniform doses across the tumor. His results suggest that the response of the tumor-associated vasculature to radiation is a major factor in tumor death or survival. In other words, treating a tumor’s vasculature—the blood vessels that surround and “feed” it—has a measurable impact on whether a tumor is eradicated (or not).

For the next forty-five minutes, Fontanella describes the premise, design, results, and analysis of his doctoral research. As he wraps up his remarks, the first slide in his PowerPoint presentation comes back around: a montage of his lab mates, plus an adorable picture of a bright-eyed mouse. Everyone applauds, and Fontanella smiles, looking visibly relieved. Dewhirst asks everyone to leave the room so that the dissertation committee can ask him questions in private.

Thirty minutes later, the door opens and Fontanella emerges. He feels pretty good about how it went, although he realized about three-quarters of the way through his presentation that he still hadn’t made eye contact with anyone in the room. “Once I did, it was good to see the encouraging faces of my friends. But I tried to avoid looking at my committee members, because if they had looked concerned I would have started worrying.” Now he waits while the committee deliberates.

At 1:54 p.m., the door opens again, and Dewhirst extends his hand to Fontanella. “Congratulations!” he says, and ushers the soon-to-be Ph.D. back into the room to receive further accolades and feedback from the committee. Official paperwork is signed and dated; Fontanella says he plans to submit the documentation to the graduate school later that afternoon.

But first, festivities are in order. Fontanella and his committee members make their way back to the room where the lunch reception had taken place, and where his friends and family are waiting. Bill and Evelyn Fontanella catch sight of their son and Dewhirst, conversing convivially, and they beam. There are hugs, photos, and hearty handshakes. Dewhirst pops open a couple bottles of champagne and proposes a toast: “To Andrew!”

Later that evening, he will gather with friends and family at Tyler’s Taproom in downtown Durham’s American Tobacco complex. “When I told people a few weeks ago to meet me there the afternoon of my defense, I specifically avoided calling it a celebration, because I didn’t want to assume too much,” he says. A smile spreads across his face, and his voice drops a bit lower, as though confessing a secret. “But I was pretty sure it was going to be a celebration.”

This summer, Fontanella will begin a joint postdoctoral fellowship/medical physics residency program at Memorial Sloan-Kettering Cancer Center in New York.