The Humans of the Wyss (HOW) series features members of the Wyss community discussing their work, the influences that shape them as professionals, and their collaborations at the Wyss Institute and beyond.
Katharina Meyer is exceptionally welcoming in both her personal and professional life. At home, this takes the form of studying and improving hosting skills by experimenting with cooking and baking. At work, it means she’s highly collaborative and enthusiastic about bringing together new members of the multidisciplinary CircaVent Team. Together, they study bipolar disorder using brain organoids and leverage these insights to identify better therapeutics. Learn more about Katharina and her work in this month’s Humans of the Wyss.
What are you working on?
I’m part of the CircaVent Team. We’re developing, refining, and improving brain organoids to study various neurological disorders, with a specific focus on bipolar disorder, where we model relevant aspects of the disorder and use our insights to identify new potential treatments.
We initially started using brain organoids to model specific aspects of the disease’s pathophysiology. And while we’re constantly improving the system, we’re now at the stage where we’re using it to better understand bipolar disorder and to generate data that can guide potential treatments.
There are a few different ways we do that. One is integrating our organoid data into AI models that identify drugs that are already used in the clinic and could be repurposed for bipolar disorder. Then we go back to our organoids to test the drugs.
The second path is using organoids to look deep into the disease mechanisms, or processes that lead to its development, and find the ones we want to target. Once we find therapeutics that could alter those mechanisms, we test whether treatment reverses signatures, or markers, of the disease.
The third approach is to study the impact of drugs known to work for some patients in the clinic, such as lithium, on our organoids, which gives us insight into the mechanisms the drugs target. Then we can try to develop drugs that would more precisely target those same mechanisms, only better and without the negative side effects that, for example, lithium has.
Soon, we’d like to generate new drugs, but right now, repurposing existing drugs gives us quicker access to new treatments. We’re very mission-oriented, so we want to find treatments for patients as soon as possible.
The speed of this approach is reflected in the fact that we’re close to starting our first clinical trial with a drug we identified through our pipeline.
What real-world problem does this solve?
We are tackling several real-world problems. First and foremost, we address the lack of effective, well-tolerated treatments for bipolar disorder.
Right now, there are different medications for treating the manic and depressive phases. But true mood stabilizers are rare, and the gold standard drug, since the 70s, to stabilize mood is lithium. However, it has a very narrow therapeutic index, meaning there is only a small range of concentrations where it’s safe and tolerable. Plus, it doesn’t work in all patients. So, it is imperative that we find better options.
Second, neuropsychiatric disorders are extremely difficult to study in human brain tissue. One reason it’s been challenging to study neuropsychiatric disorders is that before the invention of organoids, brain tissue was largely inaccessible to scientists. Through the CircaVent Project, we established organoid models of two key brain regions: the cortex, which supports higher cognitive functions, and the midbrain, a hub for emotion and reward processing. These region-specific organoids allow us to capture highly active signaling pathways in disorders such as dementias and psychiatric illnesses and to investigate the mechanisms of candidate drugs.
Finally, we address the problem of limited access to advanced organoid technology. Organoids remain highly variable today, making them difficult to use reliably outside specialized labs. To solve this, we’re investing a lot of time in automating our workflows, so the system becomes reproducible, robust, and no longer dependent on highly specialized hands-on expertise. Our goal is to democratize access to this technology so it can be used more broadly to understand and treat many more diseases and disorders.
What inspired you to get into this field?
It was pure serendipity; bipolar disorder research really found me.
I came to the United States from Germany to work as a postdoc in Bruce Yankner’s lab, where we focused on brain aging and dementia. I started learning to use induced pluripotent stem cells (iPSCs) in that context. As I was nearing completion of my work on Alzheimer’s disease, Bruce asked if I was interested in working on bipolar disorder and schizophrenia. He explained that there was a collaboration with members of George Church’s lab at the Wyss. The idea was to use our lab’s expertise to create brain organoids and provide them to the Wyss team, who would use their FISSEQ technology to investigate circuitry impairments in the context of neuropsychiatric disorders.
This opened up an entirely new direction for my research. I found the work incredibly intellectually stimulating. Neurodegeneration is, conceptually, relatively straightforward: you have neurons that die, and as they do, you lose cognitive function. In neuropsychiatry, by contrast, you often have a brain that is structurally intact and “functioning,” but functioning differently. That contrast raises profound questions: How can a molecular or cellular state give rise to behavioral differences on the scale we see in neuropsychiatric disorders? I was excited by the possibility of using organoid technology to probe those questions and started building models of schizophrenia and bipolar disorder.
Why did you want to work at the Wyss?
I really enjoyed collaborating with the Wyss team, which eventually included Jenny Tam. Once she was awarded Validation Project funding to advance the bipolar project, I started spending more of my time as a postdoc working for the Wyss. Jenny and I really clicked scientifically, and as we got better at collaborating, the models also improved.
Before getting involved in CircaVent, I had been in exclusively academic settings. At the end of every abstract, we would include a sentence about the potential applications of the science and our aspiration of moving it from bench to bedside. But it was always kind of abstract. As I learned more about the Wyss, I felt there was a more concrete way to translate what we’re doing in the lab into real-world impact.
Eventually, Jenny asked if I wanted to join the CircaVent team full-time. I loved the project and the team, so it was an easy yes.
What is unique about the Wyss, and how has that impacted your work?
I’ve had the opportunity to learn more about using my creativity as a scientist to drive impact, especially in drug discovery and development. That’s changed the way I approach my work.
In academia, there are boundaries between labs. At the Wyss, I don’t feel those boundaries; there are just researchers and platforms. There’s this real organic way of interacting and forming teams that I haven’t seen elsewhere.
Another thing that’s really unique is the spirit of collaboration. In academia, there are boundaries between labs. You sometimes feel you must be careful and are always mindful about getting scooped before you can publish. At the Wyss, I don’t feel those boundaries; there are just researchers and platforms. You can talk and brainstorm on ideas with people who have a completely different kind of expertise. As you ask questions, you realize how you can help each other. There’s this real organic way of interacting and forming teams that I haven’t seen elsewhere.
How do you collaborate with others across the Wyss Institute?
Since I joined full-time in 2022, the CircaVent team has been evolving. While working on the Validation Project, I got to mingle with other researchers. We met Bogdan Budnik, who works in proteomics. Then I saw Ninning Liu, who is part of Peng Yin’s lab, present on a technology called Light-Seq at one of the seminars. I thought it would be great to implement this in our organoids. We eventually saw that Breakthrough Discoveries for Thriving with Bipolar Disorder (BD2) was opening up a huge round of funding. We applied together and got that grant, which allowed us to expand our team and involve Bogdan and Ninning. We’ve even involved external collaborators, like the clinician Andrew Nierenberg from Massachusetts General Hospital.
With the platform’s growing capabilities and our team’s open attitude, companies and researchers often approach us to ask whether we could use our brain organoids to investigate other diseases or collaborate in different ways. It continues trickling on from there. I only wish we had infinite time to do even more of the cool ideas we’ve discussed.
What keeps you motivated and excited about your work, even in the face of challenges?
The people keep me motivated. As every researcher knows, out of every 100 hypotheses that you have, at least 99 are wrong. You have to be very resilient. It’s easier to cope with setbacks when you have good people around who are in the same boat. When you start to get discouraged, they remind you that this is all part of the normal scientific process.
Second, my curiosity only grows when things don’t work. When a hypothesis is wrong, my curiosity is further piqued. Scientific questions are riddles, and I’m in awe of what Nature has to offer that can help bring a solution.
And finally, the science itself is incredibly exciting. The data we are getting from brain organoids is cutting-edge, and especially for dynamic signaling processes, nobody has seen this before in a human brain context. We are examining the disease at the cellular, circuitry, and behavioral levels. There are so many layers to these questions, and it’s mesmerizing and deeply interesting. I know the answer is out there somewhere, so making sense of the data keeps me engaged. It always surprises me – and when it doesn’t surprise me, it means I was finally right, which is thrilling in a different way.
Scientific questions are riddles, and I’m in awe of what Nature has to offer that can help bring a solution.
What do you like to do outside of work?
Since I was a small kid, I’ve always done some form of martial arts. I started with karate, moved into boxing, tried fencing during my undergraduate years, and eventually got hooked on Sanda and kickboxing, even competing during my doctoral program. After moving to Boston, I struggled to find a club I really liked. Then COVID hit, many clubs closed, I had two kids, and I went through several injuries. Most recently, I badly hurt my shoulder while trying a new boxing club and realized I needed to find a different kind of sport. I was never particularly interested in endurance sports, but I happened to read about an alternative running style that might help prevent knee pain. Thanks to that, I was finally able to take up running as a new hobby, and almost every day I go for a run as a contribution to my own health.
Besides that, I have two small kids, and I love bringing them to museums and places I enjoy and seeing the world through their eyes. With kids, you become much more social and want to build community. I’ve wanted to get better at hosting, so I’m trying to pick up skills in that area, including cooking and baking, which I find rather soothing. I’m half German and half Asian. So, there are dishes from both worlds that I like to prepare. My mom is a great cook, so she’s provided me with a lot of tips and tricks.
What is something unique about you that someone wouldn’t know from your resume?
First, I make the best waffles and pancakes. I’m not limited by geography; I can offer the best French crepes, German pancakes, or American pancakes. My kids would agree.
Second, I mentioned that I am half-German and half-Asian. That got me curious, so I did genetic testing, and hits came up from four different continents. I expected the northern European genetic markers from my father, but I also had genetic markers from China, India, Colombia, Peru, and Africa. That left me with many questions. One of my aunts told me that my mother’s family heritage is from a very specific ethnic group called Chetti Melaka. They descend from traders originally from India who settled in Melaka, Malaysia, in the 1500s and later moved to Singapore. Given their long history of migration and intermarriage in a major trading hub, it’s not surprising that my genetic background spans multiple regions. That was very interesting to learn.
If you had to choose an entirely different career path, what would it be?
Before studying biomedical sciences, I was considering archeology. I was always interested in history and thought that it would be a cool career. But, if you ask me now, I would say a psychiatrist. Studying neuropsychiatric disorders has opened up my worldview on mental health and different aspects of the human mind. It’s fascinating how a person’s environment, in combination with their genetic makeup, can influence the human experience.
What does it feel like to be working on cutting-edge technology that has the potential to have a real and significant impact on people’s lives and society?
There are some ambiguous feelings. I’m awed by the insights into the nature of the human brain.
I feel a real responsibility to be a good communicator, to explain clearly what organoids are, what they are not, and how we think about the ethics of this research. I also see it as essential to convey the lived experience of people with neuropsychiatric disorders, so the science stays grounded in the realities of the patients we hope to help.
At the same time, I’m aware that while many people find this work fascinating, it can also make some feel uneasy or anxious. They may not know what a human brain organoid is, or they may have concerns that aren’t being addressed. Because of that, I feel a real responsibility to be a good communicator, to explain clearly what organoids are, what they are not, and how we think about the ethics of this research. I also see it as essential to convey the lived experience of people with neuropsychiatric disorders, so the science stays grounded in the realities of the patients we hope to help.