14 October 2020
Sarah-Maria Fendt, one of two recipients of the EMBO Gold Medal 2020, talked to EMBO about her work on the metabolic changes that occur during cancer proliferation and metastasis formation, her role as a mentor for young female researchers, and how she manages her lab during the COVID-19 pandemic.
Q: During your postdoc, you started to study metabolism in the context of disease. What motivated you to focus on cancer metabolism?
A: Throughout my career, I had an interest in the medical field, so I wanted to apply metabolism on something that could have a medical application. Cancer made a lot of sense to me, because when I started my postdoc, the field of cancer metabolism was rising. And I think everybody knows somebody who died of cancer: for me, it was my grandmother. We still need to understand more about cancer to be able to progress further, but hopefully, at some point, it will be a manageable disease.
Q: You have made some important discoveries about the role of metabolism in cancer proliferation. What were the key findings of your studies?
A: In cancer, fat metabolism is often upregulated, because when cancer cells proliferate, they need fatty acids to make new cell membranes. So, we looked at a specific class of drugs that inhibits the processing of fatty acids, and we found that some cancer cells can evade those drugs: the cancer cells activate a different metabolic pathway of the fatty acids, which allows them to proliferate even in the presence of the drug. It’s important to understand that such a mechanism exists: if this alternative pathway is active in some cancer patients, it might not be a good idea to use a certain inhibitor of fatty acid processing, because the cancer could just bypass it.
Q: You have also looked at the relationship between metabolism and metastasis formation. What insights did your work reveal?
A: We looked at one nutrient, called pyruvate, and we found that cancer cells that reach organs such as the lungs use pyruvate to make their metastatic niche more permissive so that they can proliferate. Scientists thought that the interaction between cancer cells and the tumour microenvironment was regulated only by transcription factors, activated for example by hypoxia. We showed that for the remodelling of the metastatic niche and thus the metastatic process to happen, cancer cells also need certain nutrients that drive their ability to nest into a new organ. This discovery allows us to better understand the interaction between metastases and their environment. At some point, we hope to be able to prevent metastases. This is years away, but it could really make a difference for patients.
Q: Some of your findings could help to increase the survival of people with cancer. How important is that your research has the potential of being translated?
A: It is very important. But if we only focus on translational research, within five to 10 years there will be nothing left to translate. Take the researchers that got the Nobel Prize for the discovery of cancer immunotherapy in 2018: they got a basic understanding of how immune cells are regulated, which, decades later, led to the development of cancer immunotherapy. We need basic-science discoveries, and if you’re in the lucky situation that your discovery helps to develop new drugs or improve the chance of cancer patients to survive, that is amazing.
Q: What is your lab focussing on now?
A: We would like to understand better how nutrients and diet influence metastasis formation, and whether they can be used to prevent metastases. Cancer patients often ask their physicians whether certain diets or supplements would support treatment. Despite the fact that certain dietary conditions such as obesity are known to influence the risk and severity of certain cancers, we lack molecular understanding and thus it is hard to give dietary advice to patients. With our research, we would like to help overcome this limitation.
Q: You have established several collaborations with researchers worldwide. How important is collaborative research for you?
A: It is essential. I like the inspiration that comes from talking to people with different backgrounds. As a scientist, the most exciting thing is to discuss with somebody who has a totally different perspective on a problem. I try to tell my team members that they should collaborate with other people, because when you bridge your own expertise with that of somebody else, you get a synergistic effect.
Q: You have established your own lab seven years ago but you already have an impressive track-record of publications. What has been key to your success?
A: Having a team of people who really care about the research and want to work together is essential. And I am very proud of my team: it’s a great bunch of people.
Q: What advice do you pass on to students in your lab?
A: One of the things that I tell my team members is that, when they ask a research question, they should design experiments that are conclusive to answer that question. And I tell them that it can happen that their hypothesis is totally wrong—that’s not a drama, it’s part of science and will reveal new insights.
Q: As a member of the LIBRA Career Development Compass, you act as a mentor for young female researchers. What advice do you pass on to women in science?
A: In many research institutes, we often have more than 50% female PhD students and postdocs. But when you look at the PI level, the proportion of women drops dramatically. I’d like to make junior female researchers aware that it is possible to become a PI. I tell women in my lab that they should believe in themselves, that their research is good and they can proudly present it. It’s so important that we support junior researchers, regardless of their gender, religion and ethnic background. Diversity is very important for any innovative process, because it generates new ways of thinking.
Q: How did the COVID-19 pandemic affect your research?
A: The biggest challenge was to shut down the lab for about six weeks. My greatest worry was about my team members, because lots of them live alone, far from their families. The most important thing was to make sure that they were doing okay, so I increased the frequency of our group meetings and made sure we could discuss about science, but also about more personal things. Now, we are working in two shifts to reduce the number of team members that are in the lab at one moment, and social gatherings are no longer possible. So, we organize things such as walks outside or picnics where we keep a safe distance from each other. And because we are not traveling, scientific interactions are limited. Virtual conferences are better than nothing, but they are no replacement for in-person conferences or meetings, so we ask other PIs to give talks in our group meetings—these are informal session where people can show and discuss preliminary data. We are trying to make the best out of this crisis.
Q: What does receiving the EMBO Gold Medal mean to you?
A: It’s a big honour, and it highlights that our research on metabolism and metastasis formation is important. It also allows me to be a role model for women in science: I hope that junior female researchers will look at this award and say, ‘this is what I can achieve.’
This interview has been edited for length and clarity.