Thursday, February 17, 2022

When Karina Kruth moved to Iowa in 2009 to pursue a PhD in biochemistry, she did so with the intention of ultimately pursuing a career in patent law. What followed were personal struggles, an unclear career path, and a realization that changed her life. In her words, when she joined Dr. Aislinn Williams’s lab as a postdoctoral scholar, she thought it would be “a short stopgap before going to law school.” Instead, she “stumbled across a life passion.”

Karina Kruth

During her second year of graduate school, Kruth married a fellow biochemistry graduate student, but less than a year later, he experienced a significant psychological breakdown and the start of what would become a seven-year-long major depressive episode that resulted in profound personality changes. Although she originally planned to start law school immediately after earning her PhD, because of her husband’s illness, she instead prioritized finding a job and reliable healthcare for the two of them. She accepted a postdoctoral position studying drugs for treating a type of leukemia.  After the funding for her project ran out, she found another postdoctoral position that lasted an additional two years, this one exploring potential drug treatments for combating oxidative damage in the kidney. “Over these postdocs I was learning things that I’d never done,” she explains. “I was out of my field completely because I wasn’t picking a postdoc based on my interests or academic career.”

After her second postdoctoral position, Kruth returned home to Nevada for eight months, joining her brother at a mining consulting engineering firm while studying for the LSAT in her spare time. “When I was in Nevada, I was like, I’m going to law school. I’m making it happen. I’ve been delayed but I’m doing it.” Returning to Iowa in what she expected to be a final gap before law school, she amicably divorced her husband and later agreed to fill his postdoctoral position at Dr. Williams’s lab so that he could start a new role elsewhere.

“We had this conversation. I said, ‘I’ll work for you for six months.’” Instead, she describes, “her lab changed my life because I get to study the thing that took my husband away from me.” Dr. Williams’s lab is housed in the psychiatry department, and her team studies the molecular and cellular mechanisms by which genetic risk factors contribute to psychiatric disease from a developmental perspective. “Say someone’s husband dies from cancer,” Kruth says. “How many people get the opportunity to study the exact cancer that killed them? And to have the qualifications and the ability to actually research it and to potentially come up with new drugs for it?”

Karina Kruth

Despite her background in biochemistry as opposed to psychology or neuroscience, Kruth explains that Dr. Williams hired her because “I’m good at cell culture. And she’s doing stem cell research and needed someone who’s good at cell culture. And she said it doesn’t matter if you know nothing about the brain. But what ended up happening is that, as I started reading about my project and researching this more, I realized that there’s a lot of biochemistry here that’s super exciting that hasn’t been done before.”

Thanks to what she describes as the “bizarre patchwork background” of her graduate work and two previous postdoctoral positions in unrelated fields, Kruth was “able to look at the information I’d learned in all three of these areas, and I realized they interconnect in psychiatric illness. These puzzle pieces come together in a way that I never would have thought of before. And what’s so crazy is I can do it. I can actually do this. And I don’t want to go to law school anymore.”

Today, Kruth is studying how glucose metabolism in the brain might relate to brain diseases, specifically bipolar disorder. In graduate school, she studied a protein called actin, which essentially functions as cell scaffolding that can grow and collapse as needed. A family of proteins called MICALs regulates actin collapse in a way that is dependent on metabolism and the redox state of the cell, which is the balance between antioxidants and oxidants. Kruth’s current grant investigates the interrelation between metabolism and these proteins in bipolar disorder. “There’s evidence that in schizophrenia, bipolar disorder, major depressive disorder, and other diseases characterized by depression or cognitive dysfunction, there’s actually a loss of synapses and connections in the brain that are important for those functions,” she says. “They don’t know why that happens, why these connections are being lost. And that’s one of the things I’m really interested in because I think it might be a metabolic switch. But the even cooler thing is that metabolism is very malleable. It’s genetically designed to be able to live in different ways and it’s very amenable to tweaking, to being adjusted by things like supplements or even medications.”

Kruth has seen metabolism’s role in mental illness firsthand. When her ex-husband was at his worst, testing revealed that he had mutations in his MTHFR gene that meant he didn’t metabolize folate particularly well. “He had an issue with the enzymes responsible for sticking the methyl on the folate. And so his doctor had him take methylfolate, which basically bypassed the methyl step. And in three days, he got better,” Kruth recalls. “He wasn’t all the way better, but he basically went from the edge to the best I’d seen him in five years, from methylfolate. And metylfolate is a B vitamin.”

Kruth recalls that she always had a “misconception that there weren’t better medications for mental disorders because it’s too complex,” but that’s not actually the case. “There needs to be more research in this area, but the research that’s going into it is bearing fruit. The problem is the field is around 20 years behind. There hasn’t been enough funding. There haven’t been enough people doing this research. There’s a lot we can do and it’s just waiting to be done. We are not spinning our wheels. We are not stuck. We are just waiting for the money and the people to do it.”

When it comes to the money, even a small amount makes a huge difference, as Kruth herself can attest. Her current research is funded by a two-year, $70,000 grant from the Brain and Behavior Research Foundation, but her first grant—the one she describes as “kicking off this whole project and allowing me to get the preliminary data to apply to the bigger grant”—was a mere $5,000 via an annual music fundraiser called AdamFest. “Five-thousand dollars might not seem like a lot when you’re in science, but sometimes it doesn’t take much. My whole career may have started as a snowball effect from a tiny grant from these amazing people at AdamFest.”

If there’s one thing Kruth hopes people take away from her story, it’s the power of this snowball effect and the existence of resources for people affected by mental illness. “People need to know about NAMI [the National Alliance on Mental Illness]. When I was going through what I went through with my husband, I didn’t know about it. and I needed them. People need to know that resources like NAMI exist, and that they can actually do something. Their money does something. There is not nearly enough money going into research about psychiatric illness, and we need to fix that because mental health issues affect everybody. Everybody knows someone or is someone who has struggled.”

As Kruth reflects on her current work and the directions she hopes to explore in the future, she is sure about one thing: she wasn’t meant to go to law school. “The number one worry that I had with patent law is the lack of the sense of fulfillment. I was worried that I wouldn’t feel like I was making a difference in the world. Patent law is an important step to getting drugs to the marketplace, but I was worrying about whether it would be enough for me.” With her current role, she doesn’t have to wonder. “My goal is to look at these people [fighting mental health issues] in the eye and say that we’re fighting for you and there’s hope. It’s not here yet but we’re fighting for you. You’re worth fighting for.”