Sergey Kornilov, PhD

What is a quick overview of your career so far?

I have somewhat of an unusual career path. I’m a psychologist - or a human neuroscientist - by training, but you found me here at ISB working effectively as a computational biologist. My background is in experimental design and my PhD is in experimental and educational psychology, not in biology. However, my first dissertation was focused oh cognitive ability; I was very interested in what makes people smart. There are many theories and I’m not going to go into the details, but one of the strong lines of reasoning (at least in Western literature) is that it’s not just your analytical intelligence, there’s more to you. I was very interested in what makes people achieve - what makes students good students and what makes writers good writers. Turns out, there’s a lot more that goes into your achievement than just your intelligence. How you think about your intelligence matters. This is all to say that my niche has transformed over time.

I was kind of interested in one of the best predictors of your achievement: language ability. Your language ability, your vocabulary, your ability to comprehend complex language, your ability to learn, your words, and your reading skills. We all differ in how well we do that.

My second dissertation was actually focused on the other spectrum of it. I started studying people who were really good, then I studied people who were really bad at something. I studied kids who have neurodevelopmental disorders of language. It’s a very underrecognized set of disorders. Generally speaking, language is something that everyone acquires very effortlessly. There is a particular convoluted brain machinery involved that some kids seem to fail develop. It manifests differently in different languages but in English, they use wrong conjunctions, tense, have effortful speech, poor vocabulary, etc. The question is why. You’re probably more familiar with autism and dyslexia, which are considered neurological disorders. Dyslexia has a very high overlap with the type of spoken language disorders I was interested in.

There is a way to measure a trait of interest over large populations using genome-wide association studies, for example, intelligence or eye color. You can see whether or not certain genetic mutations are more likely to lead to, say, language difficulties. It is somewhat difficult to do because, for a lack of better words, it’s not that it’s a garbage diagnosis but usually you’re diagnosed with a language disorder even if you have normal IQ and normal hearing (which makes it an exclusionary diagnosis). We were interested in why this happens.

We did a genetic and brain study on a bottleneck population in northern Russia. What is interesting is that about 40% have language disorders. It’s not like everyone is speaking wrong, but it’s that the speech is ever so slightly different. It goes away as you go through formal schooling, particularly in Russian schooling, but what we found by studying the brain, behavior, and genome was that there was a genetic component (not a particular mutation) pointing to a gene that we think the signal [for a language development disorder] is coming from. There have been a couple of groups who replicated our finding in a particular gene called SETBP1. It's a highly active developmental gene where something can go wrong during prenatal or early childhood development in the form of excessive neural pruning.

This brought me into a more biological space within psychology, and then I was a professor of molecular genetics in Houston before I came to Seattle. When I came, I joined a private company called Arivale. That didn’t last long. I was a statistical geneticist there and my job was to develop genetic insights (what we presented as genetic reports to people). When Arivale closed, a number of us were welcomed at ISB; so now I work on a number of projects, primarily with Dr. Andrew Magis in the Health Data Science team. I work with a lot of external-facing projects, or collaborations with pharmaceutical companies. I would say that my role primarily involves design and analytics. I started in psychology, moved into developmental disorders, moved into genetics, then came slightly back and into systems biology.

Primarily what I do now has to do with studying blood biomarkers. We have a number of projects that are investigating the efficacy of certain supplements or treatments. Our goal is to investigate different treatments for neurological disorders. It’s fair to say that we are trying to ensure multiomics is an approach that is used more widely in drug development or drug testing.

When you were researching the SETBP1, what were you hoping your discovery would be used for?

Here’s how I encourage you to think about it. You perform a study - in general, our research conduct is very regulated. You go to a population, you tell them, “Look, we’re really interested in whether or not we can find certain genetic components.” The immediate question is, “Why would we want to participate in this research?” The sad answer is that you really don’t have a reason. You [the participant] personally will not likely benefit from participating in any research unless it’s a clinical trial.

Disorders differ in how they manifest in people. Complex disorders, or so called common disorders, are slightly different. Those include obesity, language disorders, and osteoporosis. They’re not Mendelian, which means it can skip a generation. There’s no single thing you can trace them back to. Early genetic studies were very effective because you could manually trace segments that were inherited together through the pedigree. Complex disorders are not like that. There’s a huge translational gap between getting the results and knowing what to do with them.

It is now known that this gene [SETBP1] participates in brain development. It is now known that there’s a condition called Schinzel Giedion syndrome where a piece of a specific chromosome “falls off”, which happens periodically, and you get this profound genetic Mendelian condition because you’re missing a bunch of blocks of chromosome. In this case, you do not actually develop language, at least no expressive language. So clearly, it’s important. Now, does that help us treat individual kids who present these disorders? No. We will almost never know what exactly caused it in any particular person. Even if we sequence you and we found that you have some pathogenic variant, it is probably not going to inform me of my treatment approaches to you might have. The goal is to try and bridge that gap.

One of the reasons why I went to ISB was that it was a really good place to be if you want to be in an academic setting that still has real impact. As it turns out, I was in a super traditional academic setting as an assistant professor at the University of Houston. I like fundamental science but I also like feeling like I may have the possibility of changing things for people. This is why I’m interested in treatments and what predicts how people respond to those treatments.

How do you come up with new research questions? What is usually the catalyst for explorations that you conduct?

I think, initially, you only do what your advisor in grad school says. There is an emotional component to it which I think people should track very carefully. Burnout is really possible in different career trajectories. Some people have more traditional faculty positions which probably means they have been studying a circumscribed set of things for a longer time. They have developed their own research program which is usually a set of interconnected studies that are well supported by the government. I’ve decided to not make difficult choices and study things that I’m interested in while I can.

How do you deal with periods of being stumped and burnt out?

Last time I got really burnt out, I left my job at the University of Houston and I moved into a private company here in Seattle. Whether that’s dealing with burnout or a consequence of burnout, I’m really happy I made the switch. Science is not as benign as we like to portray it. It’s very institutionalized. I don’t want to say that no one cares how you feel, but it is your own job to track your mental health because nothing in science works to protect it. Pick mental health, it will probably lead to better achievement anyway.

In grad school, we idolize people who have nerves of steel and cement-like resiliency. I don’t think that’s right. That’s a culture we need to fight a little bit.

Do you find science a space where working accommodations are welcome?

There are great advantages to being a scientist. One of the advantages is that we all have a flexible schedule. It depends on what kind of scientist you are. I always enjoyed the fact that usually, when I was working as faculty, I worked two days from home. If I’m feeling like I’m cognitively not available at tackling the complexity of the environment, I might stay home and work. So, in general, scientists are very understanding of things.

Becoming a scientist means going through an institutionalized formal training program that is organized in a particular way. Throughout that program, you are usually trying to achieve a degree of competency and all that. Science absolutely does not tell you anything about that. In fact, it ignores the problem.

There’s this intermediate state when you graduate graduate school but have not yet attained any faculty position. Post-docs are kind of expected to just go with it, go with the program. No one tells them to protect their mental health and no one is willing to protect their mental health. It’s an exploited class in my opinion. A lot is expected with little in return. You have to be mindful of how you go through that. It’s true to a certain extent everywhere, but ISB is very different. Here, it’s a very friendly and kind corporate culture.

On the flipside of that, how would you deal with a poor working environment but good pay?

You have to make a choice. Do you want to be making that sacrifice or not? I am not sure I’d be willing to make that sacrifice [of being in a poor working environment with good pay]. I have tried to make that choice once and it didn’t work.

What do you think is the most valuable mistake or failure you’ve had in your scientific career?

Back in the day, we bought a really expensive piece of software to process electroencephalographic data from the brain, but it turned out there was an error in that software. I spent a year and a half analyzing my data with that software, not getting the result that I knew and I could see was there. The lesson is: be flexible and not set in your ways. Had I employed other methods to analyze these data sooner, then I would have discovered the issue sooner. In science, you don’t always find what you are looking for, and that is okay.

How did you keep your morale up after you found that you just wasted eighteen months?

Oh no, I cried. I cried real hard. You just move on. Seek social support. Sharing is caring.

When you were in college, what was a class you took that didn’t pertain to your major but that you found was very useful later in life?

I took a psychodynamic class. It actually pertained to my major but it wasn’t in the realm of my major because the class was on psychoanalysis. I mean, I find psychodynamic theory intriguing and obviously it’s on the mystical side of things in psychology as opposed to the scientific side. There are deep truths in the general approach and lives are driven by not always recognizable forces. For me to be exposed to a more volatile narrative about nature was good.

In terms of being a compassionate person, how do you balance prioritizing yourself but not being overly selfish?

There’s the pathological version of selfishness and then there’s the self caring. I think in general it’s a challenge because the world has certain roles, and we do particular dances with the people we know in the settings that we know. Breaking out of the roles is very difficult and so a common approach is therapy. It is difficult to implement change in your life. People can decline when they don’t practice self-care when carrying out any changes. I’ve not had to make difficult choices with whether or not I should prioritize myself when working recently. When I thought I had these choices, it was in fact all in my head. I think self caring is important, I think we intuitively have an understanding of when our self care becomes selfish. You do have to ignore some voices that tell you that self care is selfish.