The Epigenomic Explorer
Sitting Down With... Benjamin Garcia, Presidential Professor of Biochemistry and Biophysics and Director of Quantitative Proteomics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Congratulations on receiving the 2018 Biemann Medal at ASMS! What does the award mean to you?
It’s an amazing honor. Every person who has received this award has been an incredible pioneer in the field and has made significant contributions. I am overwhelmed to have my name on the same list as them, and to continue deserving my place on that list, I feel that I must still achieve more!
When you said, “It takes a society to raise a scientist,” in your acceptance speech – what did you mean?
In any field – and especially in science – we achieve very little alone. To become independent and rigorous scientists with the vision to ask and answer important questions, we must be trained and mentored, supported and encouraged. I definitely couldn’t have become the scientist I am without that support. Even now, I’m not doing it alone; I have a fantastic research group with scientists at all levels and from all backgrounds.
Many minority groups are underrepresented in science – how can we change that?
As a young scientist, not seeing people like you at faculty level can be discouraging. It’s a “catch-22”. We don’t have enough senior scientists from underrepresented groups and so the next generation may not think it’s an achievable goal. I cannot change the whole field, but I can work hard to bring diversity to my own lab. Diversity isn’t just a worthy goal in its own right but hugely beneficial to our work – the most creative and productive times in my group have been when the lab has been at its most diverse.
Who have been your most influential mentors?
During my undergraduate studies at UC Davis, I met Carlito Lebrilla, who has been an amazing mentor – from that first day we met, right up to the present. I came into his lab as part of a summer undergraduate research program, knowing nothing about analytical chemistry – he engaged with me, and held me accountable. I really felt that I was part of the group. He also introduced me to several well-known scientists who went on to become mentors to me, such as Jack Beauchamp, who I worked for at Caltech. In graduate school, I worked with Donald Hunt, studying tandem mass spectrometry of complex biological mixtures. It was amazing to be around a scientist of that caliber – very few people have the vision he has. He is a great mentor and knows exactly how much flexibility and freedom to give you. By that stage, more was becoming known about histone modifications, but it was all bottom-up mass spectrometry, looking at a few modifications at a time. I knew we needed to take broader approach, so I applied for a postdoc in Neil Kelleher’s group. Neil is an incredible, infectiously enthusiastic scientist, and it was the perfect training with him – both in top-down proteomics and in running a group. Lastly, David Allis (Rockefeller University), who just won the Lasker Award for his chromatin research, has been a collaborator, mentor and friend for a long time as well.
Why did you choose to focus on histones?
Quite simply, because they are such amazing proteins. I’m fortunate that the fields of proteomics and epigenetics have taken off and I’m in the crossroads of both. But I didn’t have a master plan; I just kept studying what I was interested in, without thinking too hard about what would be “fundable” in future or whether I’d be able to build a career.
What upcoming projects are you excited about?
Fifteen years or more since the role of histone modifications in controlling gene expression was first suspected, we have certainly made progress, but there are still so many unanswered questions. I’m excited about taking our fundamental knowledge and applying it to health and disease by reprogramming a diseased epigenome with small molecule inhibitors or histone-modifying enzymes. I truly believe that is a feasible long-term goal. I use the analogy of a computer: the computer hardware is your genome, but no computer works without the software to control it, and the epigenome is that software. If a virus infects your computer, you can often combat it by resetting the computer to its original state. I think we’re going to be able to do that in human disease states.
What do you hope to achieve in your career?
I won’t judge my ultimate success on the scientific breakthroughs I make or the awards I receive – gratifying as it is to be recognized by my peers. Instead, when I look back on my career, I will judge myself on the impact I have on others. Seeing those I have trained and mentored take their place as leaders across multiple fields would be more satisfying than any award I could ever receive.
Presidential Professor of Biochemistry and Biophysics and Director of Quantitative Proteomics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.