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Jonathan Kaye, PhD, (left) talks with one of his PhD students, Alyson Yeckes.
Immunologist Jonathan Kaye, PhD, keeps a floppy red hat that means a lot to him at his office in the Davis Research Building on the Cedars-Sinai campus.
It was a memento from the family of the late Charles A. Janeway Jr., MD, the immunology luminary who was Kaye's mentor when he worked toward his doctorate at Yale University in the 1980s. Janeway, who died of cancer in 2003 at the age of 60, was easy to spot at scientific meetings, with his attention-grabbing crimson chapeaus.
"He was just fabulous," Kaye said. "I couldn’t have worked for a better person. He was a thinker. He was a great mentor in a million ways and I miss him dearly."
These days, Kaye, 65, is an esteemed mentor himself. He is a sought-after adviser and a popular teacher, especially among PhD candidates at Cedars-Sinai.
Students describe him as generous with his time and compassionate, yet also someone who asks penetrating questions when it comes to work matters. "He was tough, because he wanted you to be your best," said Akop Seksenyan, MD, PhD, who earned his doctorate from Cedars-Sinai in 2013 and was under Kaye's tutelage for five years.
Seksenyan, who aspires to a career as a physician-scientist after completing his residency in neurology at Loyola University Medical Center in Chicago, said he remains in close touch with Kaye about research projects. "It's not as if I did my PhD and he said, 'All right, good luck with your stuff and be gone.' He's more like a lifetime mentor, somebody who I could talk to about anything. And it's rare to have those kinds of mentors in life where once you're past the stage where they're responsible for you, they continue to maintain that relationship."
Kaye, a professor of Biomedical Sciences and Medicine, who last year won Cedars-Sinai's Dr. David L. Rimoin Teaching Excellence Award, also wears many other hats. That includes positions at UCLA, where he serves on the medical school faculty. At Cedars-Sinai, Kaye’s roles include vice chair of the Department of Biomedical Sciences, director of the research division of immunology and scientific director of the research cores—the shared facilities that provide the specialized scientific instruments and services that would be too costly for any single lab to fund.
He "contributes a lot to the institution," said David Underhill, PhD, the interim chair of biomedical sciences at Cedars-Sinai.
"There's a kind of professor or academic scientist who is largely concerned with their own research and their own lab and their own program. And then there's another type I think of, an academic researcher who takes a much broader view of their job as being a member of the larger community and supporting the larger program," added Underhill. "And Jon is very much in that latter mold."
For his part, Kaye, whose lab is among those temporarily closed by Cedars-Sinai as a COVID-19 precaution, considers himself "primarily a scientist." But when he left his faculty position at the Scripps Research Institute in La Jolla to join Cedars-Sinai in 2009, his view of his work role evolved. "It was a change of scenery, a change of everything, and so I felt like it was time to give back to the institution. I thought they were very generous to me here, and it just sort of crept up on me."
In recent years, Kaye has enjoyed witnessing a surge of scientific interest in a small family of genes, the TOX family, that he discovered while still at Scripps. Two of the TOX genes play major roles in the development and functioning of the immune system. In particular, they regulate T-cells, which are white blood cells responsible for recognizing and responding to antigens invading the body.
Lately, some important advances in cancer treatment have involved reactivating exhausted T-cells to renew their battle against the disease. TOX contributes to the process that shuts down T-cells, so cancer researchers are interested in finding ways to partly turn it off.
Another member of the TOX family is closely tied to diseases such as breast cancer, along with brain development. "The whole family is really interesting," said Kaye, who continues to focus on the TOX genes in his basic science research.
The son of two social workers, Kaye recalls having a "typical happy suburban childhood" in the Bayside section of Queens, where he attended public schools. From an early age, he was interested in the natural world. With his older brother, Kaye would collect minerals and catch butterflies and frogs.
His interest in biology and in trying out life in California, where he had never before visited, brought him to Caltech for college.
Kaye said he was drawn to immunology because of "the complexity and the elegance of it at the same time, and the obviously incredible importance of the immune system to life. At the time, it was very much a black box. It was just not clear how a lot of it worked at the molecular level. And so, the mystery surrounding it, with the significance, I found really attractive."
After Caltech, and a stint as a research lab technician in San Diego, Kaye was off to work on his PhD at Yale, where his mentor was Janeway.
"He made a major contribution. A lot of people consider him the father of modern innate immunity," Kaye said of Janeway. "Many of us are technically good and maybe have good ideas, but he was a real thinker. He tried to draw on different things and come up with a hypothesis to fit everything."
One of Kaye's favorite memories from his time at Yale occurred close to the end of his graduate studies, when he delivered a research-in-progress report that impressed Janeway. Kaye said he doesn't actually remember what his report was about other than that "I had some grand idea of how the entire universe worked about something. It probably was mostly wrong."
"Afterward, Charlie said to me, 'You know, Jon, you just graduated.' And that was so meaningful to me. I think for him, the fact that intellectually I could come up with an idea of something that fit together these different pieces of the puzzle, was what the training was all about. And I've never forgotten that. That meant the world to me."
Likewise, Kaye's guidance has inspired his own students.
A PhD student in Kaye’s lab, Alyson Yeckes, said, he is "very accessible," and that she appreciated his willingness to provide instant feedback and have in-depth conversations.
"He's a tough questioner when you're talking about science or trying to explain something to him, but a lot of it is because he's super-interested and these are just the questions that are popping into his mind at the time,” she said. "It's coming from a place of true curiosity."
Seksenyan, the neurology resident now in Chicago, said, "the way I thought expanded tremendously when I worked with Dr. Kaye."
The experience, he said, affected "the way I approach problems, the way I analyze them more critically and look at every single detail of a result and not discard the stuff that doesn't fit into how I think things should work."
From Kaye, Seksenyan said, he learned that "every single detail is a clue—maybe the model you have in your head is wrong. With him, it's 'you've got to pay attention to these things and try to fit the model to the data and not the data into the model.'"
Those kinds of comments delight Kaye. "I would be thrilled to think that I gave even a little bit back after what people gave me," Kaye said. "That's what we all want to do, right?"