The young man in Mombasa, Kenya, was just 17 or 18 when Dr. Julie Overbaugh sat down to give him some insights into what she does so well: HIV research.
“I asked him about himself,” Overbaugh recalled. “And he said, ‘I’m the only one in my family left. My mom and my dad and my brothers and sisters are all dead from HIV.’
“What was inspiring was he said, ‘I want to do something. I want to do something with my life and I want to know how people do that’ … [Even through his loss] he wanted to be thinking about his future.”
Overbaugh, a scientist at Fred Hutchinson Cancer Research Center, is no stranger to the desire to help others. On hiatus from a Ph.D. in chemistry in Colorado, she spent four months in Oklahoma in 1982 aiding the effort to ratify the Equal Rights Amendment. And for more than 20 years, much of her HIV research has focused on people particularly vulnerable to HIV and its effects: commercial sex workers, and HIV-positive mothers and their infants in Kenya.
“She was one of the first basic scientists to join hands with clinical scientists, especially internationally, and have the foresight to see where we should be doing the research,” said Dr. Dara Lehman, a senior staff scientist in Overbaugh’s lab who also did her graduate work with her.
Overbaugh has contributed many insights into HIV transmission, the immune responses it triggers and those it evades, as well as its methods of slipping past our defenses, but it’s the relationships with people — family, colleagues, students, and friends — of which she is most proud.
There’s good reason for this. A quick poll of Overbaugh’s colleagues and trainees results in glowing responses. She’s as famed for her mentorship as she is for the quality and breadth of her research. On Dec. 1, Overbaugh, associate director for Graduate Education and holder of the Chair for Graduate Education at Fred Hutch, was recognized for her excellent mentoring with the lifetime Nature Mentoring Award in Science at a ceremony at Fred Hutch.
Trainees often seek out Overbaugh based on her reputation as a mentor, and count their blessings that earning a place in her lab also offers a chance to investigate interesting questions.
“As a mentor, she’s renowned,” said fellow Hutch HIV researcher Dr. Michael Emerman, who has collaborated with Overbaugh and shared a lab meeting with her group for more than 20 years. “Every time I go up to see her and walk past her office, she’s talking to someone in her office.”
“She made me excited about science again,” said Dr. Catherine Blish, who joined Overbaugh’s lab as a postdoctoral fellow and now leads her own lab at Stanford University, where she studies a type of immune cells known as NK cells.
“I look up to her as a role model,” said Dr. Bhavna Chohan, who first met Overbaugh in Kenya in 1993, then did her Ph.D. work in Overbaugh’s lab and now runs her own HIV drug-resistance testing lab in Nairobi. “I want to walk her path as a mentor and leader in science.”
From sports to science
Overbaugh didn’t start out dreaming of becoming an internationally respected scientist. Growing up in a large, working-class family in rural Pennsylvania, she focused on sports (the family passion) and art.
“I was not science-minded as a kid. I picked art over science classes. At the dinner table we’d talk about how we did in the game as opposed to what our grades were,” said Overbaugh, who had a vague notion that her future career would somehow involve sports.
Athletics guided her choice of college when she was recruited to play Division I basketball at the University of Connecticut. Overbaugh’s mathematical aptitude prompted a stab at engineering, but it held little appeal. Even after landing on chemistry as a major in college, Overbaugh had no grand future plan.
Overbaugh completed her Ph.D. in chemistry at University of Colorado, but ultimately she felt that chemistry “was too esoteric … I liked solving problems, but I couldn’t see the application of it. To see how science could apply to improving health was more motivating to me.”
She made the jump to Harvard’s School of Public Health and, around the same time that HIV was discovered, began studying the feline leukemia virus, or FeLV, which causes an AIDS-like disease in cats.
“And by then I liked it … I also liked the people part of running a lab. It’s not just the science — it’s the whole package,” said Overbaugh, who established her virology lab at the University of Washington in 1988. More inclined to “follow her nose” than map out a firm career plan, Overbaugh would soon expand beyond basic virology to help pioneer international, interdisciplinary HIV research. With the support of the Fred Hutch virology community and then-President and Director Dr. Lee Hartwell, she moved to the Hutch in 1999.
Virology on an international scale
Though Overbaugh honed her expertise on FeLV, she didn’t immediately leap into the hotly contentious world of HIV research. That connection came through a fellow in her lab with an unexpected link to the Nobel Prize–winning development of bone marrow transplantation by Fred Hutch’s Dr. E. Donnall Thomas: his daughter, Dr. Elaine Thomas.
“I came in to lab one day and someone said, ‘Did you know Elaine’s dad won the Nobel Prize?’” said Overbaugh, “I said, ‘Who’s her dad?’ I had no idea. I was still relatively new; she was my first fellow.”
Thomas, who was interested in moving into HIV research, introduced Overbaugh to UW’s Dr. Joan Kreiss, who wanted to study the HIV transmission risk that breastfeeding posed to uninfected infants of HIV-positive mothers. With Kenyan researcher Dr. Ruth Nduati, Kreiss, Overbaugh and a team of talented clinicians and fellows tackled a pressing question for women in an area where contaminated water could often make breastfeeding a safer option than formula. But in the era prior to antiretroviral therapy, no one knew how much risk breast milk from an HIV-positive mother posed.
“I realized that the issues in Kenya were so critical — for women, for infants, for high-risk groups — that this was a place where the science you do could actually impact public health,” said Overbaugh, who started by contributing methods to detect HIV infection to the multi-center Kenya Research Program, which involves researchers at Fred Hutch, UW and the University of Nairobi.
Initially, the collaboration, which included clinicians and epidemiologists in addition to the molecular biology expertise Overbaugh provided, was met with puzzlement by others in the HIV field — until data from their studies began coming out, she said. Now, such interdisciplinary, international collaborations are commonplace.
“She’s able to see the big picture,” said Emerman. “She looks for important questions and then sees how the materials that she and her collaborators have collected, or can collect, can answer those questions. Both the large-scale and small-scale, mechanistic levels.”
Overbaugh’s role grew from the program’s early days. After Kreiss retired, she helped foster the careers of many junior scientists working in Kenya and the U.S. Chohan, for example, initiated the team’s long-standing study of HIV superinfection, which is when an individual already infected with HIV becomes infected again with a new strain. Chohan studied superinfection in commercial sex workers in Mombasa during her graduate training with Overbaugh and before establishing her own laboratory in Nairobi. The team was the first to show how common HIV-1 superinfection could be, especially via heterosexual transmission.
The Kenya research team also found that breastfeeding could transmit HIV within an infant’s first few months, showing the high risk that breastfeeding could pose to infants of HIV-positive mothers and also that early weaning wouldn’t help prevent transmission. Once antiretroviral therapies became available, the breastfeeding trial results helped shape treatment paradigms designed to prevent HIV transmission to infants.
Still drawing on samples collected for the Nairobi breastfeeding trial, Overbaugh’s team was the first to show that broadly neutralizing antibodies, which may be able to block infection from a wide swath of HIV variants, can develop in infants within months and with little genetic tweaking. In contrast, HIV-infected adults may take years, and much genetic tinkering, to develop similar antibodies. Because vaccines need to be able to elicit broadly neutralizing antibodies in months instead of years, infant immune responses may hold clues to designing quick-acting HIV vaccines.
Overbaugh and her team also have shown that maternal antibodies that trigger direct killing of HIV-infected cells, the same type that helped provide partial protection in the Thai HIV vaccine trial, can help prevent HIV infection in breastfed babies and also reduce disease severity in children who do become infected.
“She has amazing scientific breadth,” Lehman said. “She studies everything from receptors for viral entry to differences in how gender affects the number of viral variants to antibody characterization.”
“She was one of first people to show that … sugar addition to the HIV envelope was important in terms of inhibiting the antibody response,” noted Dr. Adam Lauring, a University of Michigan virologist who began training as an M.D./Ph.D. student with Overbaugh at UW in the mid-90s and followed her to Fred Hutch in 1999. “It’s dogma now.”
Those findings “tie very nicely” into new understanding of broadly neutralizing antibodies, Overbaugh said, as many of these antibodies target sugar groups on HIV and prevent them from shielding the virus from an antibody response.
Overbaugh was also the first scientist to question whether transmitted HIV variants were somehow unique — and demonstrated a transmission bottleneck that allows only a few variants to pass to a new host and spark infection. She subsequently called for researchers hoping to understand HIV transmission and pathogenesis to focus on those variants that made this jump. The National Institutes of Health devoted $30 million to a Center for HIV/AIDS Vaccine Immunology founded on the principles Overbaugh had espoused.
As much as Overbaugh appreciates basic science for basic science’s sake, connection to Kenya helps keep her grounded. Her commitment to the country and its people runs deep. She has helped acquire funding to expand clinics to reduce trial participant wait times. She also coordinated the donation of equipment and transfer of technology that make it possible for Chohan to run molecular diagnostic tests in Kenya instead of sending samples across an ocean and two continents for analysis. Including Chohan, three Kenyan scientists obtained their Ph.D.s in Overbaugh’s lab before establishing scientific careers in Kenya.
“At a recent conference, she was introduced as an ‘honorary Kenyan’ because of her contributions to Kenyan science,” Chohan said.
Mentoring the person
“Growing up in a working-class family where we talked about people and sports and not grades and career goals, I think has made me more interested in the people and who they are and what they want,” Overbaugh said. “I don’t think there’s one formula [for mentorship].”
Her mentees cite Overbaugh’s ability to tailor her guidance to the individual as one of her great strengths as a mentor.
“She mentors different people effectively,” Laurng said. “She doesn’t have just one way of mentoring, one desired outcome.”
Blish remembers Overbaugh's lightning-fast turnaround for comments on grants and papers, as well as big-picture discussions of mentees’ career goals. Chohan values Overbaugh’s gifts in listening and providing guidance, and how thoroughly she helps students prepare for intense oral exams.
Overbaugh draws inspiration from mentorship that she’s witnessed. Dr. Maxine Linial, a senior virologist at the Hutch and research professor of microbiology at UW, took Overbaugh under her wing when she first arrived at UW. Linial nominated Overbaugh for talks at conferences and offered unflinching advice on early grants.
“There was one early grant where I told her to rip it up and start over,” remembered Linial, who now considers Overbaugh an ideal mentor choice for young scientists hoping to learn how to do high-quality research. “She did, and she got the grant.”
Perhaps one of Overbaugh’s most amazing feats is her ability to balance life inside and outside the lab. She works few evenings or weekends and finds time to get outside every day. Still close friends with her fellow graduate students from Colorado, Overbaugh meets them for yearly backpacking reunions. Because of the value and perspective Overbaugh gains from her time outside the lab, she also encourages her lab members to take time off or try a new project if they’re running into frustrations at the bench.
The effects of Overbaugh’s scientific endeavors stretch around the globe, from drug-resistance testing labs in Kenya back to rural Pennsylvania, where her always-supportive parents never quite understood what she did. But after they attended the ceremony where then-First Lady Hillary Clinton bestowed the Elizabeth Glazer Scientist Award on Overbaugh, her father voted Democrat for the first time.
“Even though they didn’t understand the particulars of my day-to-day, they knew I was doing something important,” she said.
Sabrina Richards, a staff writer at Fred Hutchinson Cancer Research Center, has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a Ph.D. in immunology from the University of Washington, an M.A. in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at srichar2@fredhutch.org.
