The PostDocs Forum

Principal Investigator, Brent Stockwell, is our Featured Scientist of the Month. Brent, author of the recently published The Quest for the Cure is currently an Early Career Scientist of the Howard Hughes Medical Institute and an Associate Professor at Columbia University with joint appointments in the Department of Biological Sciences and the Department of Chemistry. Visit his lab page and follow Brent on twitter.

Please share a bit about your current research, how did you first become involved in science?
I first became interested in science in high school, when I really enjoyed chemistry and physics. I took Astrophysics and Particle Physics courses at Columbia on Saturday mornings through their Science Honors Program, but in the end it was chemistry that attracted me the most. I went on to study chemistry and economics in college and then decided I liked it so much that I would pursue a PhD. My current research involves defining mechanisms governing cell death, particularly as it relates to cancer and neurodegeneration.

Your upcoming book “The Quest for the Cure: The Science and Stories Behind the Next Generation of Medicines“  discusses ‘undruggable proteins’. Can you briefly explain what ‘undruggable proteins’ are and what sparked your interest in this topic?
Drugs act by binding to (i.e. interacting with) specific proteins in an organism. It turns out that all known drugs interact with just 2% of the proteins in humans, leading many to speculate that most of the remaining proteins are not the kinds that readily interact with drugs. Thus, despite the fact that many of these proteins are key regulators of disease, they don’t seem to be capable of interacting with small molecule drugs. We got interested in this problem in my lab because we use small molecules as tools to study biological processes and as potential drugs. We began to face this challenge that most proteins don’t seem to be amenable to modulation with drug molecules. Most people just dismiss these challenging proteins and focus on the readily druggable proteins. I thought this was an important issue to bring to the general public–to explain the challenge of targeting these proteins with drugs and some of the forefront research in this area.

As the PI of a lab, what are the most common problems you face in lab on a day-to-day basis?
The 3 key resources that make a lab function are people, money and space. At different times, each of these can be become limiting, but mostly the biggest challenge is to recruit outstanding people and convince them to work on the questions that the PI finds interesting. There are many small administrative issues that have to be dealt with regularly as well, but this is just part of the business of science. The exciting part is working with my labmembers to think of the ideas, then do the experiments and analyses that will illuminate answers to questions we find interesting.

What was the most challenging or memorable situation that you personally faced in the lab?
I’ll contrast two events, one of which I mention in the book. When I was a graduate student, I was trying to devise a way of activating a particular protein in cells, and I had spent about two years engineering different proteins and small molecules that might be effective. I finally had an effective system, but then I did one last control experiment, testing what should have been an inactive version of the compound I was using. The control compound was just as active! I repeated this several times to be sure, and I initially joked that I had done one too many controls. But my advisor reminded me that the point of science is to uncover the truth about nature, not to publish papers. We were ultimately able to solve this mystery and it was profoundly satisfying (and it led to 2 papers instead of 1!).

So sometimes a result that seems exciting disappears when the right controls are run. In contrast, when I was a Fellow at the Whitehead Institute, we were testing many thousands of compounds for their ability to selectively kill tumor cells with a particular mutation. We didn’t find anything very interesting in the first large set of compounds, but there was one weak effect. I considered ignoring it and moving on to other projects, but I decided for the sake of completeness to test this compound again, and each time the effect was more striking. This eventually became an extremely interesting compound that is the subject of a major project and a major NIH grant in my lab. So sometimes a seemingly small effect can turn into something very important. One just needs to have the judgement about which effects to follow up on and which to set aside.

What do you think is the most important personal characteristic for a researcher?
I think creativity is extremely important–being able to come up with unusual hypotheses and technologies that provide a new avenue to address outstanding questions. But of course creativity is of little value without hard work and good organizational and people skills.

What is the best advice you could give to someone who wants to have a career in academia?
The most important thing to do is find an area of science and a question that really excites you. At the end of your career, what will matter is not the number of papers published, or awards garnered or money raised. It will be that you answered some questions that were extremely interesting to you and a small number of like-minded people.  If you are enthusiastic about your science, I find that the resources and career success will follow, at least to a sufficient extent to allow you to continue doing what you enjoy.

Can you share any tips for lab management and organization?
It is crucial to have good time management skills. I like the 2×2 matrix approach: there is the urgent/not-urgent axis and the important/not-important axis. You should try to spend all your time in the non-urgent/important quadrant (i.e. working on your next grant application 3 months ahead of time, planning your next seminar 1 month ahead of time, planning your major scientific goals for the year). But too many people end up in the not-important/not-urgent quadrant (email, chatting with random passerbys, phone calls, non-necessary service work etc), until they find themselves in the stress-inducing urgent/important box (grant is due tomorrow, seminar is tomorrow, lab is flooding). It is hard to stay in the right zone, but if you can do it, you will enjoy yourself a lot more.