Judy Campisi elected to the National Academy of Sciences for her pioneering work on cellular senescence

Being elected to the National Academy of Sciences is a widely accepted mark of excellence in science and is considered one of the highest honors a scientist can receive. Buck Professor Judith Campisi knew she had been nominated for membership based on her pioneering work on senescent cells, which drive chronic inflammation and are associated with aging, tissue degradation, and promotion of disease. But Campisi didn’t think she’d make it into the organization this year, given that it often takes several tries for nominees to make the grade. The potential award was not on her radar screen. So, when Buck President and CEO Eric Verdin called her early in the morning on May 1 to congratulate her on the award, Campisi answered, “What award?”

At an employee champagne party that afternoon, Campisi — to the surprise of no one who knows her — gave all the credit for the achievement to the people who have worked in her lab.

A jagged road to success – the first in her family to attend any type of college
Campisi’s backstory is not typical of most scientists and should provide comfort for parents of bright teens who appear to have no sense of direction. Campisi — who attended an all-girls Catholic high school in New York City — didn’t have a clue what to do with her life in high school. She had no one to advise her, either in her middle-class family or at the school. “Because we didn’t have that much money, I knew I pretty much had to stay close to home, and the local college had these little two-year curricula. At the bottom of each course description was the number of males and females in the class,” she says. “And my guiding principle was that I wanted to be where the boys were — and that was science, it was chemistry. I said ‘sign me up.’ I was pretty good at it, but my motivation was, unfortunately, teenage hormones.”

After completing the two-year program, Campisi got a low-level position at a local pharmaceutical company. She got bored, quit, and tried her hand at a variety of jobs, everything from pumping gas to being an editorial assistant at a small-town newspaper. She took off on an extended road trip with a girlfriend. She was often unemployed. “I’m really glad I took the time,” she says. “At some point, I realized I didn’t want to spend my life being un-gainfully employed. I remembered that I did enjoy chemistry, aside from the boys.” She went back to school and started to fall in love with science as she was completing her four-year degree. “It was challenging, it was dynamic. Nothing is static in science.” After getting her bachelor’s degree, she went straight to graduate school.

Taking chances early in her career
Campisi got her PhD in biochemistry from the State University of New York at Stony Brook. She landed a postdoctoral fellowship at the Dana-Farber Cancer Institute in Boston in the lab of Arthur Pardee, an early mentor for Campisi and one of the fathers of the cell cycle. Pardee was very passionate about cancer biology. Campisi jumped into a field she knew nothing about.

Campisi says Pardee gave her great advice when she got her first faculty position at Boston University Medical School in 1984: Pick a project that’s not mainstream. Campisi says oncogenes, which drive cancer, had just been discovered and everyone was jumping on that bandwagon. “I decided I should try to study the flipside because my lab was small and all these giants were working on oncogenes. I decided to study why we don’t get cancer, which was tumor suppression,” she says. “Not only was it very interesting, it was less competitive, and I thought it would give me a chance to make a dent in the science.” She was right. What she didn’t know was that the work on tumor suppression would lead her to study aging.

Colleagues at Boston University who were studying aging encouraged Campisi to consider a large potential project that, in part, would explore senescence, a known tumor suppressor, as a potential contributor to aging. Campisi says no one thought the idea would go anywhere, but she helped write the grant application, and somewhat surprisingly the project got funded. “The more I worked on senescence, I thought, ‘It is true. Senescence does contribute to aging.’” But Campisi says the link to aging was far from obvious.

Great science takes time
Campisi’s “aha!” moment about senescence came in the mid 1990s, but it took another five years for her to prove herself right.

Campisi recalls that in the early 90s many researchers were trying to link senescence and aging by focusing on the fact that senescent cells stop dividing. They were studying secretions from the cells in the context of cell proliferation based on the hypothesis that the secretions caused the cells to stop dividing. For Campisi, some of the gene-based connections they were trying to make didn’t add up. What made more sense to her was that the secretions came after the cells stop dividing, and that the secretions inflamed neighboring cells. “The light bulb went off,” she remembers. She thought to herself, “The link to aging is not based on the fact that these cells stop dividing, it’s based on the secretions. They affect the surrounding tissue. That’s what aging is about.”

Two editors, one from Cell and the other from the Journal of the American Geriatrics Society, asked Campisi to write what she calls “prophetic papers” in 1996–97 setting forth her theory of aging. It took five years to get the data to show how this might happen in a mouse. That study appeared in the Proceedings of the National Academy of Sciences of the United States of America. In 2008, her team described what’s now known as the SASP — the Senescence-Associated Secretory Phenotype — in PLoS Biology. It’s one of the most cited papers in biomedical research.

Connecting with the Buck
Campisi was recruited to the Lawrence Berkeley National Laboratory (LBNL) in 1990 when her focus was still mostly on cancer. By 1999, she was running the Department of Cell and Molecular Biology and co-directing their Center for Research and Education on Aging in conjunction with the University of California, Berkeley. In 2001, the Buck’s founding President and CEO Dale Bredesen reached out to Campisi to ask her to join the Institute’s Scientific Advisory Board. “I told him I’d rather be part of the faculty,” Campisi says. She opened a small lab at the Buck in 2002 and moved all her operations to Marin in 2009.

“Even though I had great colleagues, nobody at LBNL was that interested in aging,” says Campisi. “It was frustrating because it was hard to have informed conversations.” Since coming to the Buck, Campisi has been involved in numerous collaborations with other faculty and often travels internationally to talk about her science. “It used to be ‘what’s the Buck?’ Now we’re so well-known and recognized around the world,” she said. “Honestly, there really isn’t another place that is of the same philosophy, caliber, and structure as the Buck. Don’t get me wrong —there is great aging research being done all over the world. But bringing that greatness together in the way it’s done at the Buck, I haven’t seen it.”

Unity Biotechnology — moving the research into the clinic
Campisi’s science is poised to move from the lab bench to the bedside via Unity Biotechnology, which incubated at the Buck and launched in 2016 thanks to the company’s first CEO Nathaniel David, a biotech entrepreneur who recognized the potential of the science. A drug that selectively eliminates senescent cells is currently in phase I clinical trials. The first two age-related diseases on the company’s radar screen are osteoarthritis and glaucoma.

Campisi is a scientific co-founder of Unity. “I always hoped that something we did would be useful, but I honestly didn’t think it would happen, not based on what we were doing in the lab,” she says. “Being involved in getting a drug ready for the clinic is a high that I never thought I’d experience.”

Campisi says Unity’s drug is designed to cause chronically present senescent cells to simply die and go away in a manner that does not impact surrounding tissue. Preclinical work in mice has successfully addressed a number of age-related diseases, including osteoarthritis, glaucoma, cancer relapse and metastasis, and chronic lung disease. Given that many age-related diseases are driven by chronic inflammation, the possibilities of impacting human health are significant.

New explorations in the lab
Campisi is far from running out of ideas. Her lab is focused on a deeper understanding of the SASP with an eye toward developing more focused interventions. Some of her team of approximately a dozen scientists, postdoctoral fellows, and students are working on cellular senescence as it relates to muscle and the heart. She’s also branching out and looking at other cell fates that may or may not be related to cellular senescence. She’s interested in the signals that tell a cell it’s time to die. She’s also intrigued with cell identity and the fact that new stem cell technologies make it clear that cell identity is malleable. “Is rejuvenation possible at the cellular level? And should we intervene?” she wonders.

A road not taken (fortunately for us)

When she was really young, Campisi’s fantasies of the future ran the gamut. She wanted to be a ballerina, a kindergarten teacher, or an FBI agent. As a young adult, she seriously considered becoming a musician. She played a couple of stringed instruments and was in a folk-rock band. She did occasional gigs and got paid, albeit minimally. She and her sister played at the New York State Fair. Even though she loved music and its adventurous lifestyle, Campisi’s practical nature guided her toward a different path. “I was surrounded by musicians who had a thousand times my talent, and most of them were waiting on tables or pumping gas,” she says. “What I learned is that if you want to make a career in music, you have to be extraordinarily lucky and rank in the top 0.001 percent of your peers. To make a good living in science, you still have to be lucky, but the top 1 percent is good enough. I had a thousand-fold better chance of success in science.”