The cell doctor: Q&A with Joan Brugge

If you could solve one big problem in cancer research, what would it be?
Prevent cancer’s recurrence. Despite all the advances we’ve made in cancer therapeutics, too many patients must deal with the news that their cancer is back because of resistance to therapies. Drug resistance is complicated by tumor heterogeneity—this includes heterogeneity between tumors from different individuals, but even more significantly, within an individual tumor and between tumors at different sites in the same patient. Tumors are challenging to control and we need to better understand why drugs that are effective at treating tumors initially, still leave patients vulnerable to relapse.

How is the Ludwig Center at Harvard addressing this challenge?
We brought together the best brains from across the Harvard community to work together to accelerate progress in identifying cancer cells’ vulnerabilities that we can target therapeutically and develop new strategies to overcome therapy resistance. We’re all committed to providing a deeper understanding of the causes of therapy resistance as well as ways to intervene and monitor it. This unique collaborative research model encompasses a diverse cross-section of experts in cancer research and cancer biology as well as oncologists, pathologists and immunologists. Every Monday morning we spend two hours sharing ideas and presenting data and then brainstorming about what the data means and where to take it next. Right now, our efforts are focused on melanoma, small cell lung cancer, acute myeloid leukemia and triple negative breast cancer— cancers where current therapies work well initially, but in which the tumors inevitably recur.

You spent several years in industry. What motivated you to make the move?
I was very excited about the overall objectives and approaches that the start-up company was aiming for—using structure-based drug design to develop inhibitors of protein-protein interactions, which is an ongoing challenge in designing drugs. I felt that it would be very satisfying to do discovery research in an environment where it could be translated into something meaningful for patients. For me it was an opportunity to take my research to the next level and use my different talents and skills in developing drugs designed to inhibit the proteins we had identified and discover pathways crucial for disease processes. And, it would all happen under one roof.

What advice do you have for someone contemplating a move from academia to industry?
There are many exciting and challenging jobs in industry that would be very attractive to research-oriented scientists. Before you make the leap, weigh the pros and cons of the potential move. You may love research but you may be leery about running an academic lab because of the many demands on your time. Industry scientists generally have a better work-life balance and can stay focused on their research without the added commitments of teaching, advising students, publishing and applying for grants that come with an academic job. At the same time, industry research is geared towards a product rather than knowledge itself and a product-driven mission means that research freedom can be limited. A company has to prioritize their efforts and activity, which means they’re focused on the information that they “need to know versus the things that would be nice to know.” Academic investigators have the flexibility to investigate a promising lead and pursue those odd findings that don’t fit the norm. That being said, many companies allow investigators to carry out independent research for a small percentage of their time, allowing them to engage in more risky research. Bottom line, industry environments vary considerably and you need to assess your own strengths and weaknesses and decide the best fit where you’ll continue to excel in what you love to do and enjoy most.

How can we reach out and draw more young, bright minds into science?
Schools are so focused on teaching to the test and preparing students to score well, that there’s no time to work on projects that would awaken them to the thrill of discovery research. Real learning is achieved through the investigative process and kids have to be encouraged to search for the answers themselves. Science classes should be geared toward understanding a topic and less about memorizing facts. If we teach students to think like scientists – let them test an idea, evaluate evidence, ask a question about how the world works and perhaps discover how difficult it can be to find an answer, I think we could get more kids hooked early on.

How do you unwind outside the lab?
Tennis and scuba diving. Weekly tennis games are the perfect outlet to take my mind off work and allow me to enjoy friendships outside of work. Scuba diving is just a phenomenal, awe-inspiring experience. There is something about neutral buoyancy that is very spiritual and allows you to experience this incredibly beautiful world around you. Nothing rivals the experience of being suspended weightlessly in water while floating effortlessly along a coral reef. And there’s nothing quite as exhilarating as swimming next to whale sharks, which we did in Raja Ampat—it’s one of life’s ultimate bucket-list experiences.

Do you think more attention should be paid in training scientists to communicate effectively?
Absolutely. Communication is part of a scientist’s everyday life—giving talks, writing papers and grants, and communicating with different audiences. But for a lot of our trainees, English is their second language, which can be challenging, especially when writing a scientific paper or presenting research orally. Communicating complex ideas in a clear, transparent way is an essential tool and we need to find more opportunities for postdocs to practice and hone their skills. I have my lab members ‘practice’ their writing skills by drafting reviews of manuscripts being considered for publication; this is a very effective way to encapsulate their thoughts and distill the research down to just a few paragraphs and to use their critical thinking skills.

What’s on the cancer horizon?
Right now we’re looking at a very complex scenario for cancer treatment—especially in terms of precision medicine. There is an enormous diversity within a tumor—different regions have different mutations—and we need to identify predictive markers for the cancer state rather than for every genetic alteration within a tumor. We need to develop therapies targeting a cancer’s state as opposed to trying to sort out the optimal therapy for every genetic alteration or combination of genetic alterations. Immunotherapies are going to play more and more of a role in cancer therapy and we need to have a critical understanding of how immunotherapies should be integrated with targeted therapy and how we can optimally design immunotherapies in order to avoid more generalized immunostimulation.

How do you inspire creativity in your lab members?
Breakthrough research requires the confidence to try things out, take risks and make mistakes. When my lab members are working on a project, I give them a great deal of independence in allowing them to be the first to interpret the data and propose the next steps. If there’s another direction I think they should consider, I ask rather than tell. Asking the right questions encourages them to shift gears and dig deeper, with the goal of finding a new or alternate way of approaching and solving a problem.

How do you achieve career-life balance?
Juggling the demands of a career and a personal life is an ongoing challenge for me, and I have to admit I’m not very good at it. The overwhelming demands on my time are a constant struggle. I feel that it is important to engage in recreational activities in order to get a break from work; however, one has to prioritize because it isn’t feasible to participate in all of the things in which you are interested. At work, consider all the demands that compete for your time, and decide which ones to keep and what to discard. Take on only those commitments that you know you have time for and that you truly care about. This way you will get satisfaction from these commitments, people will respect you for the job that you get done and they will understand when you say no to other requests. It’s a discipline that doesn’t come naturally to most of us, especially me.