By Delia Ward 

Olga Afanasiev, Ph.D. ’13, is multi-tasking: talking on the phone while waiting for her toddler to wake up. More generally — like a lot of fourth-year medical students at this time of year — she’s between residency site visits. Afanasiev is also part of UW Medicine’s Medical Scientist Training Program (MSTP), an eight-year educational program in which students earn both an M.D. and a Ph.D.

Olga Afanasiev, Ph.D. ’13, displays a sample of a T cell-treated tumor while visiting the lab of her mentor, Paul Nghiem, M.D., Ph.D.

“I was trying to decide: should I go to medical school, because I really liked medicine and interacting with patients?” Afanasiev says. “Or should I go to graduate school and do science?” When a mentor told her she could do it all — that there were programs designed to accommodate both interests — she applied to the MSTP at UW Medicine.

Think about the now

Entering into an eight-year program is a major commitment. The first two years of medical school are followed by four years spent working on a Ph.D. Then come the final two years of medical school — and, probably, several more years spent in residency.

“The program is for people who find it really exciting to function at the interface of what we know and what we don’t know,” says Paul Nghiem, M.D., Ph.D., an MSTP mentor in the Department of Medicine’s Division of Dermatology. “That dual preparation is incredibly empowering and fun and exciting.”

Preparation for a future career in translational medicine is an admirable goal, and 86 percent of UW Medicine’s MSTP graduates have remained engaged in research throughout their careers. The director of the MSTP, Marshall S. Horwitz, Ph.D. ’88, M.D. ’90, Res. ’92, points out, however, that these young people are in school during their most productive years. They have a lot to give while they’re learning.

“I try to tell our students: don’t just think about the future. Think about the present. You can do great things right now,” says Horwitz.

“I try to tell our students: don’t just think about the future. You can do great things right now.” ­— Marshall S. Horwitz, Ph.D., M.D.

Doing great things: the HIV transmission project

“Everyone that I interviewed said, ‘You should really meet Julie,’” says Caitlin Milligan, an MSTP student finishing up her Ph.D. That’s Julie Overbaugh, Ph.D., a virologist and immunologist who studies HIV at Fred Hutchinson Cancer Research Center.

Overbaugh has a reputation as a great mentor, and her lab was doing work in infectious diseases, a topic in which Milligan was keenly interested. And the lab combined “really great science” with population-based studies, a real selling point. Milligan decided to work on the topic of mother-to-infant HIV transmission: why do some babies contract HIV from their mothers, but others not?

She focused on antibodies, one of the immune system’s basic tools. When women are pregnant, their antibodies pass into the womb, where the infants receive them. Milligan set out to find if these antibodies helped protect children born to HIV-positive mothers, and, if so, which characteristics of the antibodies were protective.

Overbaugh praises Milligan’s work, now being evaluated for publication. “This is an important question related to HIV vaccines and HIV prevention,” Overbaugh says. “Caitlin designed a very elegant study that took advantage of the samples we had banked, clinical information, and her laboratory training, which allowed her to tackle this problem from a broad perspective.”

The results of the study are promising. Infants with higher levels of ADCC (antibody-dependent cell-mediated cytotoxicity, a mechanism of the immune system) had slower disease progression or increased survival rates. “This suggests that eliciting ADCC antibodies might be an important component of a vaccine,” says Milligan.


Photos of Afanasiev and Nghiem: Clare McLean; photos of Milligan and Overbaugh: Robert Hood, Fred Hutch

Making connections

Approximately one-third of MSTP students are like Milligan — they choose a mentor at Fred Hutchinson Cancer Research Center, UW Medicine’s primary MSTP partner. And students also are encouraged to seek additional mentors for further guidance. Milligan, for instance, collaborated with other researchers to learn more about epidemiology, statistics and infant immunology.

Afanasiev had similar opportunities. Her primary mentor was Nghiem, who studies Merkel cell carcinoma (MCC), a rare and deadly form of skin cancer often caused by a virus. However, she spent roughly half her time in the first two years of her Ph.D. working with David Koelle, M.D. ’85, Fel. ’92, a viral immunologist at UW Medicine.

“I was learning the immunology techniques that would allow me to answer pressing questions in the field of Merkel cell tumor biology,” says Afanasiev. And the work paid off. Several major cancer- and immune-related journals published her and her colleagues’ findings on MCC, and her work helped pave the way for a larger clinical trial. (Read about Afanasiev’s work on Merkel cell carcinoma.)

Caitlin Milligan discusses her project, which investigates antibodies and mother-to-child HIV transmission, with her mentor, Julie Overbaugh, Ph.D.

Afanasiev says her timing was lucky; she came on the scene just when Nghiem’s lab was beginning to pursue an interesting direction. Nghiem also would point to Afanasiev’s ability to relate to scientists and physicians — and to patients.

After she returned to clerkships and started her rotations, Afanasiev met a 40-something woman suddenly and unexpectedly struck down by end-stage liver disease. Unfortunately, there was nothing to be done to change her condition. But Afanasiev spent time with the patient, and with changes in medical staff, she became the family’s most familiar and comforting point of contact. The patient felt so close to the MSTP student that she asked Afanasiev to help plan her daughter’s wedding. Everyone in the hospital room started to cry.

“Even at the end of life, even with no therapy options available, we can still make a difference in patients’ lives and in their families’ lives,” says Afanasiev. “That connection can be healing.”

Benefiting humanity

What inspires an already busy person to be a mentor in the MSTP? They enjoy it immensely.

“The students are just a blast,” says Overbaugh. “It’s fun to train people who are brighter than you.” Overbaugh, who also serves as an associate director for the MSTP, notes that her lab benefits from her students’ work — and that helped convince her to become an administrator for the program. “As faculty, it’s our responsibility to contribute to the programs that benefit our research,” she says.

“The program sets you up for serendipity.” — Paul Nghiem, M.D., Ph.D.

It’s clear that students like Milligan and Afanasiev have made major contributions to UW Medicine’s and the Hutch’s research enterprise. What’s less clear is exactly what MSTP students will go on to do with the tools they’ve been given. Medicine changes enormously over time, and breakthroughs are unpredictable. When Nghiem was in medical school, for instance, Merkel cell carcinoma had not yet been identified as a distinct disease. “It’s hard to know where people will have an impact,” Nghiem says.

But have an impact they will. Horwitz reflects on the program’s 215 alumni — developmental biologists, biotech entrepreneurs, genomic scientists — people who, in some way, are benefiting humanity. Like all good teachers, he feels a sense of pride.

“Every time they publish something, or make a scientific breakthrough, or do something great, you feel like you’ve had a role in it,” says Horwitz.

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