Jonathan Sebat
As a young college graduate, Jonathan Sebat pursued music, playing drums in a Portland-based indie rock band. Today, the 38-year-old Shasta High School graduate is on the cutting-edge of genetic research, called “one of, if not the most promising molecular geneticist in the country,” by one of his colleagues.
“It wouldn’t surprise me if his mom and I were buying tickets to Stockholm someday,” said Sebat’s admittedly proud father, Frank, an intensive care physician in Redding for 25 years who now directs the cardiovascular intensive care unit at a Visalia medical center.
Sebat, an associate professor of psychiatry at the University of California at San Diego, leads a national research team that recently made a breakthrough discovery of a gene mutation common to a small percentage of patients with schizophrenia. The study results were published Feb. 23 in the journal Nature, and Sebat was subsequently interviewed on National Public Radio’s “All Things Considered.”
His team’s latest finding is one in a string of leading genetic discoveries related to psychiatric disorders they’ve made since 2004 using microarray technology, a technique used for scanning the human genome to look for mutations.
“The technology was new, but it was the first time anyone had begun to use it to catalog mutations of the genome,” said Sebat, who started the schizophrenia research with the help and support of Nobel Prize winner James Watson, co-discoverer (with Francis Crick) of the structure of DNA. “We’ve published four papers that have had very far-reaching impact on the field of genetics and psychiatry.”
In 2007, when Sebat was a geneticist at Cold Spring Harbor Laboratory in New York, he was co-leading a team that linked autism – which, like schizophrenia, is a brain disorder — to changes in a wide range of genes. Published in the journal Science, the study caused a lot of excitement among autism researchers, National Public Radio reported.
Another groundbreaking study published in Science in March 2008 linked schizophrenia to certain types of genetic glitches. (Read an NPR synopsis here.)
February’s cutting-edge discovery was built on the foundation of the earlier schizophrenia study.
“This one is important because as time goes on we have ever-larger patient samples to work with,” said Sebat, who moved from New York to the San Diego medical school about a year ago to have more access to patients. While the 2008 study sampled 150 people with schizophrenia, this study involved 16,000 samples.
Without getting too technical, here’s what the study involved: Using microarray technology, Sebat’s researchers found a spot on chromosone 7 where patients had extra copies of a gene called VIPR2. Having that extra copy causes a higher level of expression of that gene, which is a receptor that binds to a neurotransmitter. That neurotransmitter is involved in regulating learning and behavior in animals.
“There’s some basic neuroscience behind this gene that makes it interesting,” Sebat said. “It’s also a potential drug target – chemicals have been developed which actually work to inhibit or turn on this receptor. That’s an exciting possibility here. This is personalized medicine in action.”
While Sebat’s team has been successful in finding gene mutations linked to autism and schizophrenia, those only explain a fraction of the causes, he said.
“That’s the reality you have to face when you’re talking about brain disorders,” he said. “There’s lots more to learn about what genes are involved.”
A scientist’s life
Despite the vast, global impact these genomic discoveries could have, life as a geneticist is far from glamorous. Though he’s been interviewed on National Public Radio, Sebat said he’s made no TV appearances, and not many articles get written outside the scientific community.
But the satisfaction that comes from the work is enormous.
“I’ve been so blessed in that I’ve had multiple opportunities to look at a result that just came out of a lab and realize at that moment that I’m the only one in the world who knows this, and this is actually going to change the field as we know it,” Sebat said.
And what exactly is that kind of moment like?
“It’s what you call a ‘eureka’ moment, but you don’t actually stand and shout, ‘Eureka!’” he said. “You power down your laptop, get in the elevator, go to your car in the parking lot and drive home at 2 in the morning staring at the yellow line and enjoying the moment.”
Research, Sebat said, “is a marathon, a constant slog all the time. There’s never a point where you cross the finish line and everybody cheers. It’s not unlike a bike race. At the end, there’s literally three people standing there cheering for you because nobody would drive out and stand in the desert for hours waiting for you.”
Growing up in Redding
Sebat’s parents have cheered him on his entire life. Linda Sebat, who was a family law attorney in Redding for 18 years, said part of her parenting philosophy was to talk to her three sons (Jonathan is the oldest) about setting career goals and how to accomplish them. Frank Sebat said he was strict with his boys about working hard and telling the truth.
The Sebat brothers, Ben, Christian and Jonathan
All three brothers graduated from Shasta High School in the ‘90s. Middle brother Benjamin is a construction management project engineer in Orange County; Christian, the youngest, is doing a pulmonary critical care fellowship at UC Davis.
- Jonathan Sebat and wife Lilia.
Jonathan is married to Lilia, also a professor of psychiatry at UCSD, and they have two children: daughter Dalia is 6; son Demian is 2.
Jonathan Sebat's children, Dalia and Demian.
Frank and Linda, who now divide their time between Redding and Visalia, chose Redding as the place to raise a family in part because it reminded Frank of the rural, river-split Illinois town where he grew up. “I wanted to try to recreate for my kids what I had experienced,” Frank said.
Jonathan recalls hours spent exploring the Bureau of Land Management territory that bordered their western Redding neighborhood and riding his bike everywhere, including an epic trek from Redding to Arcata.
When he was in elementary school, the family did its first extensive backpacking trip in the Trinity Alps Wilderness (Frank joked that they used to call them “family ordeals”). Paring down, they packed only two tents in case it rained – which of course it did, Frank said.
But such moments only bonded the family.
“I remember walking out over Bee Tree Gap with those three boys, and I just started crying,” Frank said. “I thought, you’ll never be able to recreate this. It was the most free and interactive time.”
Jonathan’s independent streak showed up on that trip, his father said. “He went off on his own and caught a fish. I didn’t even know he knew how to fish.”
Music became a passion for Sebat when his father bought him drums when he was 10. Some of his most vivid Redding memories were the do-it-yourself rock concerts put on by area high schoolers.
“Summer concerts were done commando-style: carloads of people would show up unannounced at an outdoor amphitheater somewhere in Redding, set up their instruments and play until the cops showed up,” he said.
Sebat admits it took time to find his career path. He hated high school biology but found physics fascinating (“It was the first time I felt like I had a natural talent for anything, other than football” he said). He decided to pursue science and enrolled in a biology program at UC Santa Barbara. But he got turned off by the medical track and decided he’d rather go into research.
“I wouldn’t say that I was ever very serious about science ’til I got to grad school,” he said. And grad school waited for a few years while he pursued music with some of his former Shasta High classmates. In 2002, Sebat earned his Ph.D. in genomics from the University of Idaho and completed his postdoctoral training at Cold Spring Harbor Laboratory in New York, where he earned several awards.
What’s next in the lab
Part of Sebat’s team is already working on developing drugs that would target their latest gene mutation finding. The researchers engineer mice with extra copies of the VIPR2 gene, first to figure out what aspects of brain function are affected, and then trying to correct using compounds that are active against the VIPR2 receptor, he said.
Most of his researchers continue to work on genetic sequencing, projects such as developing comprehensive gene catalogs of children with autism – “a new frontier for our lab,” Sebat said.
Funding for the research comes from the National Institutes of Health and private foundations that support mental health research.
Frank Sebat describes his oldest son as a “pure scientist and a smart scientist.” He’s also able to recruit good workers, organize a lab well, and get good production from researchers. “Some researchers flounder because they might be a rocket scientist but not have good interpersonal skills,” Frank said. “Jonathan’s both.”
Sebat said he is motivated by the thought that someday doctors will be able to take a patient, scan their genome, find the cause of their disorder and come up with a reasonable idea about how they could be treated.
“These types of genomic approaches are going to transform medicine,” he said. “I hope to see a family shattered by mental illness be able to come back together because of something we did.”
Candace L. Brown has been a newspaper and magazine reporter and editor since 1992, including eight years at the Redding Record Searchlight. She lives in Redding and can be reached at candace.freelance@gmail.com.
