Was there an event or person that inspired you to pursue a career as a scientist?
“I was always drawn to science. I went to a local, non-prestigious public high school in Pennsylvania where not all the academic work was rigorous However, there were a couple science teachers that challenged me and stoked my interest in science. Given my interests in both chemistry and biology, pursuing biochemistry at the next stage was a relatively clear choice. I had a great undergraduate experience at Notre Dame doing organic synthesis research that further solidified my interest in understanding the chemical basis for biology. After a few unexpected moves around the country, I was very fortunate to pursue my PhD under the guidance of Dr. Jack Dixon at UC San Diego. Jack is a stellar biochemist who just kind of knows how biology works. My post-doc mentor, Dr. Vamsi Mootha, was equally inspiring for different reasons. Vamsi is a quintessential systems biologist, geneticist and mathematician. The large-scale skills I learned from his mentorship proved to be a great complement to my reductionist biochemistry background. Throughout it all, I just followed my nose. It was always the natural path; I didn’t over think it.”
Was anyone in your family a scientist? “My parents were the first to go to college in their families, my mom became a nurse and my practical-minded dad sought a fast path into a stable career, which led him into dentistry. He rushed through college in three years before enrolling in a top dental school. I think if he did things again, he’d might like to do something like what I do. My parents were very encouraging of we [my brothers and I] wanted to do, as evidenced by our current careers: a chef, a theologian and a scientist. Our professional diversity leads to some interesting conversations. One time, my chef brother, called me and said, ‘tell me about transglutaminase’ (which, I learned, is sold in the culinary world as “meat glue”)! I think both of those domains [cooking and science] underestimate the analytical and artistic sides of the other. In cooking, there’s a lot of science, and in science, there’s a lot of art. People have the misconception that science is rigid, but of course it’s not just that — you have to be creative and adventurous.”
Did you ever want to do anything else? “I don’t think I ever seriously considered something beyond science for a career. But, if I had to switch, I think I might be drawn to design work or architecture. But I think I could be happy doing a lot of different things, especially things that involve both intellectual pursuits and craftsmanship. I really liked working and learning both with my hands and my head as a trainee. That’s what I miss most being a PI — practicing the art with my own hands.”
What are the most exciting projects ongoing in the lab? What are the ‘big questions’ you’re pursuing
“We bounce back and forth between very large, open-ended questions about the nature of the mitochondrial proteome and focused questions into discrete proteins and pathways. We try not to be overly myopic by focus too much on one thing or to be too diffuse. I’m excited about mapping how mitochondrial proteins work and how the incredibly complex mitochondrial machine is built. Making a mitochondrion is akin to constructing a bacterium in the middle of a cell. You need to orchestrate transcription, translation, import, and assembly of more than 1000 proteins encoded by two genomes. I think there is a lot to learn about the protein functions undergirding these processes. Once built, there’s crosstalk between pathways, moonlighting functions for core metabolic proteins, such as TCA enzymes affecting mitochondrial protein translation. We focus a lot on coenzyme Q, a remarkable redox-active lipid that supports many biochemical processes throughout the cell. There is so much still to uncover about how it is made, how it moves around the cell, and what protein functions it supports. Overall, my favorite thing to do in science is to create interesting new datasets that then help us discover something fundamental about how a protein works. I’m always happy when we help assign functionality to an orphan protein, especially when it is linked to a human disease.”
Where do you see yourself and your lab in 10 years?
“I’m a basic scientist at heart. I like exploring how things work. But one reason I moved to WashU five years ago was that it has a very vibrant medical community with many clinicians that are very interested in basic science. I’d like to see if some of the things we’re doing can have translational impact, whether that’s through a spin-off company or just via clinical applications of our work. I am also open-minded to pursuing new biochemical themes. We’ve been focused on mitochondria, but now we’re chasing pathways that lead into and out of mitochondria in interesting ways. I like following the data, letting it guide us where to go. I also like playing off of the interests and expertise of the people who join the lab. We have members with very different background — neuroscience, bioinformatics, biophysics, genetics, medicine, chemistry — it changes what we do. If a great chemist comes into the lab, I’ll think differently about what projects we might do. It's good to think about a grand vision, but I also think that can be overrated. I often think that’s not how academic science works and that it can stifle creativity. You need to stick to types of problems you like to solve but you also need to find fertile ground. I think we need a good portion of academic scientists to just bang around, find interesting things, and establish reliable nuggets of information about how nature works. Sometimes, to plan it out more than that either backfires or constricts you.”
What are activities and hobbies outside of science that you pursue?
“Ha, I guess whatever my boys happen to be into at the moment. We really enjoy playing different kinds of games — board games, card games, video games. I’ve also decided to learn guitar and skiing as an adult. It’s hard, but I think it’s good to have hobbies throughout your life where you’re a novice. It helps you remember what it’s like to be a new trainee in science and how hard learning new things can be. My family and I also love to travel and do anything outside. We’ve been able to travel together through Spain, Germany, and Australia recently in trips linked to scientific conferences. Are either of your sons interested in science? “I think my younger son (14) is more inclined to the kind of biological science I do, but who knows; my older son (17) is very into liberal arts but is also finding that he loves calculus and physics. I’m excited to see where their passions take them.”
Outside of your specific field, what area of biology or broader science do you find yourself thinking about lately?
“There are a few topic that always seem to draw my attention when I’m perusing a journal, such as microbiology. It’s very interesting to me how microbes often invent different ways to perform complicated biochemistry. The way our cells do biochemistry isn’t the only way. Understanding how other organisms have solved similar or different biochemical problems can be very informative and motivate new tools or drugs. I also like chemical biology — building chemical tools to ask biological questions, which returns me to my undergraduate orgo days.”
What question do you wish people would ask you about your work but rarely do?
“I think that working on mitochondria is a double-edged sword in that it’s familiar to everyone — it’s an iconic structure in cell biology and everyone remembers the “powerhouse” moniker — but as a result people think we know everything about it. The question would be: what do mitochondria do that I probably don’t know about. There are a lot of surprising answers to that question and more to come.”