Transitions in development – an interview with Peng Du

Let's start at the beginning, when did you first become interested in science?

When I was in high school, I was thinking about what kind of career to go for. I thought becoming a professor seemed good because I could do research I am interested in and train students who can contribute a lot to society. I ended up doing biology at Shandong Normal University in the Shandong province in 2002. As it wasn't a top-tier university and Shandong is a tiny province, I worked hard to improve myself and to learn more about biology. Gradually, I decided I wanted to pursue a career in biological sciences.

What made you decide to do a PhD at Peking University? And what did your research focus on?

That was a tough decision for me. I had to pass the national postgraduate entrance examination to join a university, and only had one chance to choose a university I like. Peking University is one of the best universities in China for biological studies. From Shandong Normal University, where I obtained my bachelor's degree, there were only very few students who had passed the exam to join Peking University for their PhD studies before. I put in a lot of effort to pass the exam and was eventually successful in going to Peking University in 2006. I was really proud, even now. So were my parents, as they didn't think I could do that at that time!

My supervisor, Dr Li Yi, is a famous Chinese plant virologist. I worked on a special RNA regulatory pathway called the small RNA-mediated post-transcriptional repression pathway. I studied how the plant and the virus interact by using small RNAs as repressors. Actually, several studies in my lab are still focusing on the RNA silencing pathway.

After that you went to Harvard Medical School as a postdoctoral researcher. What prompted you to go to the USA?

For the last two years of my PhD study, I went to UC Riverside, California, to do a joint project in another lab, led by another plant scientist, Shou Wei Ding, who is a friend of my PhD mentor. After that, I went back to China to finish my PhD thesis. I really enjoyed my two years in California. I became familiar with the US research style. I wanted to improve myself and explore a new research field beyond plant science, so I decided to move my research from the plant virus into the mammalian system and apply for a postdoc position in biomedicine at the Harvard Medical School.

Could you tell us more about your work during your postdoctoral research?

Eventually I reached out to Richard Gregory's lab because their research focusses on microRNAs, a type of small RNA, in stem cells and in tumour cells. The molecular pathways overlapped with my previous research experience, but the system was different. That helped me to smoothly move to a new field. In the Gregory lab, I worked on molecular regulation of microRNA pathways in mouse embryonic stem cells (ESCs) and identified an intermediate microRNA biogenesis step and the complexes that mediate the production of the microRNA intermediates, named pro-miRNAs. This study was eventually published in the journal Cell (Du et al., 2015). After that, I kept working on this unique miRNA regulatory pathway, and interestingly found that it governs a unique pluripotent state, poised pluripotency, which represents the transient embryo state at peri-implantation stage. This follow-up study was published in Cell Stem Cell (Du et al., 2018).

In 2018, you returned to Peking University to start your own group. What made you decide to go back to Peking University?

I really liked the US life and the research culture, where I could freely research on anything I wanted to. That's why, initially, I wanted to stay in the US as a PI. By my fifth or sixth year in the US, I started to think about how I could find a PI position in the US and whether I would fit in to the American academic community. On the other hand, I heard that the Chinese government offers really good support for young, early-career scientists. There are many special grants for new PIs, with good startup packages from the university. I talked to different Chinese scientists, and I started to think that maybe I could start my lab smoothly and quickly in China. It is common in China for a new PI to have 15 to 20 people in their lab within the first five years, unlike in the US. That was the main reason why I decided that China could be a good choice for me to set up my lab.

Can you summarise the research themes of your group?

Our group has three research directions. First, following on from my previous postdoc research, we are looking at RNA regulatory pathways in the context of stem cell development. We try to apply our knowledge in molecular biology to understand stem cell differentiation and embryonic germ layer specification. Our second research direction is studying totipotent stem cells. We are trying to develop a new culture system to condition and develop these totipotent stem cells into functional cells, such as liver cells and hematopoietic cells, and try to apply these cells in regenerative medicine. Our third research focus is interesting because it is a bioengineering project that connects my PhD and my postdoc studies. We are trying to reconstitute a plant immune protein, called RNA-dependent RNA polymerase 1 (RDR1), in cancer cells. We found that this protein can repair the defective microRNAs and repress the proliferation of all types of cancer cells. Like CRISPR-Cas9, people managed to apply a system in bacteria to the mammalian genome. I hope we can use plant systems in mammalian cells and explore their potential applications in medicine.

How did you navigate the field to find your niche?

When I finished my first postdoc project, which resulted in my Cell paper in 2015, I was only in my third year of postdoc. I didn't think that I should become independent then because the system I used was quite similar to what I did before. I decided to expand my research focus and shift to stem cell research, because moving from chemistry to stem cells required me to understand the biological questions in a different way. When I came up with my second project, I felt I had a different opinion and motivations from my postdoc mentor, Richard, because he is a pure biochemist. Although his lab uses stem cells as a system, the lab never really did stem cell work, they only used the stem cells as a cell line to understand the RNA regulatory pathways. I felt that I could use my previous molecular and chemistry knowledge in researching questions in stem cell biology. That's when I decided it was time for me to move on to find my own platform to realise my own ideas. When a lot of new PIs start their own lab, they want to stay safe and work with systems they are familiar with. But I wanted to break out of the biochemistry field. That's why I started working in the stem cell research field and even taking on a bioengineering project. I'm always trying to find new ways to expand my research focus. That is what I feel a challenging part of becoming a new PI was for me. I'm lucky I found my way.

What are the current exciting areas in stem cell biology?

I find regenerative medicine exciting. Although we see that stem cell biology is used in treating human diseases, until now we have not really used that many different stem-cell-derived functional cell types in human, because it's not easy to control cell fate or function in vivo. If we can apply the hematopoietic stem cells or functional liver cells in a patient, we can help a lot of people. In our lab, we try to use the totipotent stem cells we captured recently to differentiate into functional cells. Maybe in the future we can govern particular differentiation pathways to engineer various functional cells for medicine, like CAR T cells. That is an exciting area in stem cell biology.

What advice would you give to people starting their own labs?

Looking back at my experience, I think the most important aspect of starting a lab is the PI themselves. The PI has to guide the students towards the right direction for a project. That's the PI's main duty. Secondly, a new PI has to learn to communicate with students efficiently, to make sure everyone is on the same page. That's why in my first three or four years, I met with my students, one-to-one, once a week. That way I could know the progress of the project and also get to know the students, their characters and how to best work with them. Being a PI is very different from being a postdoc, when you only have one project. Now I need to handle five or six different projects, and I need to organise different members in the lab to work together as a real team. That's why effective communication is key. My third piece of advice is that the new PI needs to be motivated to apply for new grants right from the beginning. It's also useful to attend conferences to increase your exposure and communicate with the community about your findings.

How do you approach hiring new team members?

In the beginning, I didn't have much experience hiring students. Now I have developed some criteria. When a new potential student comes to my lab, I'll tell them that one thing I really, really care about is that they have the motivation to be a good scientist. The students cannot be satisfied with just learning techniques and doing experiments – they need to think of the biological questions and the bigger picture of the whole project. We have rotations for a student to find their favourite lab and for PIs to find wonderful students at Peking University. During this process, I always try to find students who are motivated and are able to think of the questions they encounter in their own projects.

How important do you think mentorship is in navigating an academic career?

I think mentorship is important – I learned a lot from my previous supervisors. My PhD mentor, Dr Li Yi, really trusts his students. He lets young students handle the whole project. That helped me become independent and establish my own scientific opinions. My postdoc mentor Dr Richard Gregory is a pure and very smart biochemist, and I really like his approach to science. He can find small details from a large set of data. He's very good at finding clues to solve a problem. My two mentors, from looking at the big picture and focusing on the research details, have taught me how to handle all the projects in my group.

Did you ever consider an alternative/non-academic career path?

Not really, at least not for now. One of my students graduated this year. He's the first author of our Cell paper last year where we found that a plant immune protein can elicit a broad anti-tumour response. He's just started a company to translate that discovery into treatments, and I am also involved in this company. But for the most part, at least for the next 10 years or so, I still want to focus my attention on academic research.

Let's move outside of the lab – what do you like to do in your spare time?

Although I work most of the time, I like to play basketball as a hobby. I find that relaxing.

Peng Du was interviewed by Joyce Yu, Online Editor at Development. This piece has been edited and condensed with approval from the interviewee.