Thomas Vierbuchen is a developmental biologist who studies brain development using stem cells. He joined the Developmental Biology Program in the Sloan Kettering Institute in 2018. In an interview in April 2019, he spoke about his path to becoming a scientist and how his own experience as a cancer survivor has shaped his approach to research.
I grew up in the suburbs of Charlottesville, Virginia, where I went to a small private high school. There wasn’t much going on in town, and my family didn’t travel much, so I was excited to go to a big city for college. That’s how I ended up in Philadelphia at the University of Pennsylvania.
I wasn’t exactly sure what I wanted to do, but I knew I could never have a normal nine-to-five desk job. I wanted to find something that was more exciting, like maybe being an FBI agent or an investigative reporter. Those professions are actually similar in some ways to being a scientist. You’re digging into something and trying to figure out the various connections between different events or components.
I don’t remember having an epiphany about becoming a biologist. For a period in college I thought I would go to medical school. Then I took a class in cancer biology at Penn. It was taught by a researcher named Brian Keith, who had built a reputation as an incredibly good teacher. He encouraged us to go to the seminars for the cancer biology graduate department. They invited some amazing researchers for these seminars. Hearing them talk, it seemed like biomedical research was an exciting career that would be more interesting than being a doctor. Based on that, I decided to apply to graduate programs.
I went to Stanford University as part of its cancer biology PhD program, but after my lab rotations, I ended up working in a lab that was focused on stem cell biology and brain development. For my postdoc, I wanted to learn more about the regulation of gene expression during neural development. I went to Mike Greenberg’s lab at Harvard Medical School. He is one of the pioneers of studying gene expression in the brain and specifically how sensory experience shapes or instructs changes in gene expression in developing neural circuits. Somewhat ironically, given that I was in a neuroscience lab, I ended up primarily working on basic mechanisms by which signaling pathways that are implicated in cancer regulate gene expression changes and changes in cellular behavior.
So my path took some turns: I went to grad school for cancer biology and ended up working on brain development. Then I went to a neurobiology department and did something that was perhaps closer to cancer biology. Now I have my own lab at a cancer center and am using pluripotent stem cells as a model system to understand how signaling pathways switch genes on and off in the developing brain. In a way, that seems quite fitting.
From Patient to Researcher
I have a personal connection to biological research. I had Burkitt’s lymphoma when I was a postdoc, about four years ago. I was treated initially, but then the first round of therapy didn’t work. I had to go back and be treated again a few months later. Having spent this time as a patient further reinforced for me that there was still so much we needed to learn on a fundamental level about cancer. Our lack of knowledge about the basic functioning of normal cells and cancer cells is a limitation in our search for better cancer treatments. I strongly believe that basic research is central to the fight against cancer.
Burkitt’s lymphoma is known as a very curable cancer, but you have to take large doses of cytotoxic chemotherapy. This treatment is effective but aggressive. It can have severe short- and long-term consequences. And doctors can’t easily give this therapy to people in developing countries because you need to be near a first-rate hospital in case of infection or another complication. Even with a highly curable cancer, we have tons of room for improvement. This is why basic research remains so important. It builds the foundation necessary to develop the next generation of therapies for cancer and other diseases.
The Most Complicated Organ
My lab at MSK is interested in how information encoded within the genome orchestrates the process of building the brain, which is one of the most complicated organs in the body — probably the most complicated.
It’s made up of a huge number of distinct types of neurons that work together to form neural circuits. These circuits allow us to think, feel, behave, learn, and remember our experiences. How the brain gets built in the embryo and how the information to build this complex structure is encoded within the genome is an extremely interesting and complicated question.
The focus of what we do in the lab is understanding how genes turn on and off at the right time and place in order to produce this huge diversity of cell types and also to keep neural circuits running throughout life, including the ones that allow you to learn and remember your experiences.
We use pluripotent stem cells from mice and humans to try to reproduce specific steps during brain development. It’s not possible to study the human brain with primary samples from humans. Pluripotent stem cell models are the best window we have into how the human brain develops and how the human genome encodes specific features of the human brain that are different from other species.
Many diseases, such as autism and schizophrenia, are thought to have a basis in brain development. By understanding how human neurons develop and specialize, we hope to learn more about the molecular mechanisms that underlie these devastating mental illnesses.
A Special Place
The Developmental Biology Program at the Sloan Kettering Institute is maybe less well known to the general public because we’re thought of as a cancer research institute. But it’s one of the best programs of its kind in the world. I can’t imagine a better place to be doing what I’m doing with the colleagues that I have. Having excellent colleagues at Weill Cornell [Medicine] and Rockefeller [University] next door makes it a very exciting scientific community to be a part of.
Developmental biology plays into cancer because many types of cancer are essentially just a derangement of normal developmental processes or a continuation of those processes when they shouldn’t be happening.
In my lab, we want to go after important questions that aren’t necessarily easy to solve. Nowadays there’s pressure to go after tractable problems. Having the support that SKI gives us means that we can really try to make transformative advances. This is what is required if we want to develop fundamentally new treatments for disease. “Go big or go home” as they say.