My scientific career started at the movies. It was an action movie. I was in fifth grade, and we watched a film about mitosis. I only knew a little bit about cells at that point. We were learning that DNA contained our inherited genes, and that DNA was organized into chromosomes, which were equally distributed to daughter cells during cell division. The movie showed the chromosomes lining up and then separating into two cells, and I was floored! I thought there had to be little machines in there that duplicated and condensed the chromosomes, and then moved them around when ready. From then on I knew I was going to pursue science.
As I grew up, I thought about whether to follow a path into research or medicine. I loved biology, but the discipline was very descriptive at the time and didn’t appeal to my mechanistic sense of inquiry. So, I majored in chemistry at Lewis & Clark College in Oregon. Chemistry provided a molecularly detailed canvas, and I had the opportunity to work in a laboratory. My thesis topic was biological but used chemistry, because I studied how neutrophils, a type of immune cell, make the toxin superoxide to kill bacteria.
It was technically challenging. The experiments had to be done dry under nitrogen, so as to avoid quenching by oxygen or water. I think it is very important that undergraduates are offered research opportunities. These are the years where you’re first making decisions about your future, and textbooks and lectures don’t provide the full spectrum of science, especially about how discoveries are made. I think it’s critical to have lab experience and try the discovery process first hand. For me, I was totally hooked.
After college, I spent a year as a laboratory technician to learn the “new” recombinant DNA technology of the time. I then went to graduate school at Stanford in the department of Structural Biology where I worked in the laboratory of Roger Kornberg, who would win the 2006 Nobel Prize in Chemistry for his studies of the molecular nature of gene transcription in eukaryotes. Here I discovered chromatin remodeling complexes, which play an essential role in chromosome structure and biology: SWI/SNF and the more important RSC, which open up and remodel chromosomes to regulate gene expression.
At present, my lab has continued to dissect the component and mechanistic bases of chromatin remodeling, especially that of the RSC complex, with respect to specificity of gene expression regulation and timing, and how this process is altered in cancer cells. We also use zebrafish to explore how chromatin structure changes during the development of germ and egg cells and during fertilization, and how this influences embryogenesis. Similarly, we also study sperm chromatin to better understand its contribution to embryonic development. Finally, my lab is now working to understand how chromatin regulation is affected by cellular energy supply and status, such as during starvation and stress, which has implications for the behavior of tumor cells.
What drives me today is the same inquisitiveness I had as a boy. I am just a curious guy, and I just want to know how things work. I am fascinated by nature. When things make sense, it is wonderful. When we discover the cellular engineering and its regulation, and how logical it all is, it is fascinating. I just love it all.