Yael David is a chemical biologist with an interest in epigenetics — the study of how proteins, small molecules, and other factors lying above the genome can influence which genes in a cell are expressed. She joined the Chemical Biology Program in the Sloan Kettering Institute in September 2016. We spoke with her in April of 2018.
I have a drive that comes from being trained by a very strong military dad, who was a combat pilot in the Israeli Air Force. He would always tell me, “If you’re the smartest person in the room, you’re in the wrong room.” This attitude kept me moving forward and pushing outside of my comfort zone.
My mom is an educator at heart and a very compassionate person. She taught me to be a good, empathic person and productive member of society. I think that’s why I have this clash in me, of being very driven but also trying to see beyond the destination and paying attention to how I carry myself and how I treat the people who share the journey with me.
When I was 17, my dad was offered a job in New York, right before I was about to join the military. In Israel, military service is mandatory, but more importantly, it was my civic duty, so I stayed and joined the Israeli army. The huge responsibility of my position and living on my own forced me to grow up and become independent very quickly. During my army service, I fell in love with using bits and pieces of information to try and construct a full picture.
Speaking Two Languages
During my professional journey, I have moved between Israel and the United States several times. I started my undergraduate degree at Tel Aviv University. Once my parents settled on Long Island, I stayed with them. Stony Brook University had a fantastic biochemistry and neurobiology program, which was where my interest lay.
The two years I spent at Stony Brook were extremely stimulating. During my first semester, I did hands-on research in the lab of Lonnie Wollmuth. We were studying the structure-function relationship of neuronal receptors. I was fascinated by neurobiology, and through that, I discovered my true passion: how proteins work.
On one of my visits to Israel during these wonderful years, I met my husband, Yaron. He was an academic officer in the midst of his military service and therefore bound to Israel. For that reason, upon graduation from Stony Brook, I moved back to Israel and joined the Weizmann Institute of Science on a direct PhD track. I studied ubiquitin biochemistry under the supervision of Ami Navon. Ami was an incredible mentor and helped harness my passion for science and encouraged me to study biological questions “because curiosity demands.”
In this productive period, I realized how powerful chemistry is, but also that biologists aren’t taking full advantage of it. After graduation, I accepted a position in the lab of Tom Muir at Princeton University. In Tom’s lab, I dove headfirst into chemical synthesis and learned for the first time how to make molecules. It was a very empowering feeling. But it wasn’t only the technical aspect that was exciting. Tom taught me how to think about biological questions with a chemical resolution and an interdisciplinary toolbox.
After my postdoctoral training, I could not pass up doing science at a top-notch place like MSK, which has a rare combination of high-quality science and the opportunity to do translational research. Now in my own lab, I’m taking everything I learned throughout the years and tackling complex biological questions with powerful chemical tools. Being able to speak both languages, I can build tools and use them to bridge chemistry and biology.
Bringing New Tools to the Study of Epigenetics
My lab undertakes a unique and interdisciplinary approach to a convoluted problem: how cells with an identical DNA blueprint can regulate gene expression to generate the diverse mix of cell types in the human body. We focus on epigenetic mechanisms of gene regulation and try to understand how misregulation of epigenetic events leads to disease states, such as cancer.
We are particularly interested in studying how histone proteins, which spool the genetic material, help regulate its accessibility to the transcription machinery and participate in determining cell fate. We utilize chemical synthesis to manipulate histones in living cells, mimicking epigenetic changes, and examine the direct effect of this manipulation. In fact, we are now going beyond the single cell to perform these manipulations in live animals, which opens exciting avenues in epigenetics research.
Another focus is studying how changes in the cellular environment are reflected on histones. These changes, for example in the metabolic state of a cell, are associated with aging as well as an array of conditions, such as diabetes and cancer. We recently found that these changes can damage histones and affect the integrity of the DNA, which can contribute to cancer.
Perks of the Job
My favorite part about my job is that every day is an adventure. I go to work excited about the people I am going to meet, the scientific challenges I will encounter, the new ideas I am going to brainstorm. I love that my days are packed, but every once in a while, I enjoy just closing my office door, turning on my music, and allowing myself to think, What are some of the interesting things I want to study? Where does “curiosity demands” lead me?
My students sometimes get annoyed with me for having too many ideas. But I always say it’s better to have more ideas than hands, because if it’s the other way around, you’re in trouble.
At some point in grad school, I was working on this protein that no one knew almost anything about. I found that it had an uncharacterized function. I spent about six months on this project, and it was very exciting. Then one day we discovered that our protein was contaminated. That was the source for its activity. It was heartbreaking.
That’s when I established my one-day rule: I’m allowed to feel bad over a scientific disappointment — but only for one day. After that, I have to get up and dust myself off. It’s such a slippery slope that if you don’t put hard lines around how much you can feel sorry for yourself, you’ll never stop. By the way, my one-day rule also applies to scientific successes — one day of celebration and then back to work!