Transitions in development – an interview with Jingli Cao Free

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

I have been interested in science from a very young age; in the 1980s, before starting elementary school, I lived with my grandparents in a small village, where they were farmers. Growing up on a farm, I learned to appreciate nature, animals and plants; they were my friends. We also didn't have electricity at the time, so staring into the sky at night was my only entertainment. So, I watched the stars, the Milky Way and the meteorites. I wondered why stars are bright, why they have different colours and how far away they are from us. I wished I could know more about them one day. Then, when I was five years old, I left the village and moved to a small town to attend elementary school, where I began to gain more knowledge. Here, the questions in my mind did not decrease, but instead increased. At the time, I had fish and shrimps as pets, and so I knew that shrimp could regrow lost legs and I thought that was fantastic. So, biology, physics and astronomy were all interests of mine as a child, and it was a difficult decision choosing which one to pursue. When I attended Shandong University (Jinan, China) for my undergraduate degree, I ended up choosing biology as my major, because I felt this was a direct way to understand the fundamental basis of life.

I understand you did your PhD at the Shanghai Institute of Biochemistry and Cell Biology. What did your research here focus on?

The Shanghai Institute of Biochemistry and Cell Biology is part of the Chinese Academy of Sciences. As a graduate student there, I joined Dr Xueliang Zhu's lab, where I studied epithelial polarity, cell cycle regulation and ciliogenesis; it was quite a broad range of topics. I've therefore worked with many cell types and with multiple animal models, including mouse, zebrafish and Xenopus. For my thesis, I focused on ciliogenesis, the formation of the cilium, an organelle found in eukaryotic cells that works like an antenna to transduce signals into the cell, propel cell movements or drive fluid flow over the cell. Ciliogenesis requires a conversion of a mother centriole into a basal body, followed by cilia elongation, and my research focused on how these processes are regulated. I discovered a microRNA called miR-129-3p that controls primary cilium formation by downregulating the centriole protein CP110, as well as targeting multiple actin regulators to suppress actin dynamics. This was the first evidence of a microRNA targeting proteins directly involved in cilia formation. We then went on to knock down this microRNA in zebrafish and we saw ciliopathy phenotypes, such as a curved body and defective left-right symmetry. Overall, I found this research experience to be very fruitful; I learned a range of techniques and experienced multiple model systems, and this formed the basis of my future research.

You then made the big move to the USA for your post-doctoral position at Duke University. What made you decide to move there and, more specifically, to join Kenneth Poss' lab?

When I graduated from my PhD, I decided to study regenerative biology to solve the question that puzzled me as a kid: how can shrimp regrow their legs? I was fascinated by the remarkable regenerative capacity of the zebrafish heart, and Dr Kenneth Poss is a pioneer in using zebrafish as a model to study regeneration. So, I emailed him, he responded quickly and we had a very engaging chat over Skype. We realized we were a good match for each other and so I was lucky enough to join Ken's lab. It was one of the best decisions of my career; I was given plenty of freedom to explore different research directions, and Ken also guided me through the transition into independence. We still chat very often to discuss my research and my progress as a group leader, and I really appreciate his support. Recently, we even published a paper together in Development, and we continue to collaborate to this day.

You then started your own lab at Weill Cornell Medicine in 2018: what were your most important considerations when you were looking for group leader positions?

I think having a collegial and supportive environment was a main consideration. Here [at Weill Cornell Medicine], we have a tri-institutional environment, including Weill Cornell Medical College, Rockefeller University and the Sloan Kettering Institute, so this is a collaborative niche of biomedical research. If you want to find a collaborator, you can always find someone researching a similar topic that fits your needs within these institutions. We also go to seminars across the three institutions quite often. Additionally, we have the Cardiovascular Research Institute, or CVRI, which was founded in 2016 by Dr Geoffrey Pitt (the director of CVRI). CVRI has recruited four junior faculty members, including myself, and is still expanding. I think there is a strong commitment from CVRI and Dr Pitt towards promoting young investigators. These are the reasons that made my decision to move here an easy one.

How was your experience of transitioning to a group leader? Do you have a best or most challenging moment in this process?

This is my dream job, and although the transition was hard, it was enjoyable. Not everything worked out as I expected; I was not trained to hire people, to manage a lab or to make a budget. I'm still learning from my colleagues and also learning from my failures. However, this job comes with the freedom to study what I like, which makes the process really enjoyable. There have been several best moments and they are all small things. For example, I'm satisfied whenever I unlock a new skill as a group leader, such as hiring the first lab member, submitting the first grant and publishing my first independent paper, which was published in Development. The biggest challenge, however, was running the lab during the pandemic, which started when my lab was barely more than one year old. When the medical school was shut down, we had to euthanize around half of our zebrafish colonies, and we were not able to recover to pre-pandemic levels until after a year. So, it was a significant loss of both our time and funding. Luckily, we have recovered now though!

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

Each person has their own story and faces different challenges. So, my first piece of advice is to have a mentoring committee. When I joined Weill Cornell, I was told to assemble a mentoring committee, something Weill Cornell do for young group leaders. This included my department chair, the CVRI director and also senior principal investigators, including Dr Todd Evans, who is familiar with development biology and working with zebrafish. They read my grants and manuscripts, and provide constructive critiques. Together, they guide my progress in all aspects of a starting a lab. It's easy to take a course to learn these things, but when you start to do that work, it could turn out to be very different; working with my committee members made the process very smooth. Second, I think talking to people who recently started their own lab a couple of years before me was really helpful. These people have recent first-hand experience; they know how things work, how difficult it is, and what challenges you will face and how to address them.

What is your approach to hiring new team members?

I feel like this is the most challenging work to do as a group leader, so I did a few things to help with the process. First, I made a lab website that describes our work in detail, as well as life in our lab, including many photos showing how enjoyable life in the lab is; I think that attracted potential candidates. Second, I posted job adverts on Twitter and other community websites, such as the zebrafish information network (ZFIN). I also talk to friends and colleagues who might know someone looking for a position. Lastly, when choosing who to hire, I think picking someone who cares about the lab and who is willing to work with the group is extremely important; a one-on-one meeting with the candidate is an essential step in gauging this. You want to make sure the lab members will be able to work happily with this candidate and that they will integrate well into the team.

Can you summarise the research themes of your group for our readers?

My lab aims to understand how tissue regeneration is regulated at the cellular and molecular level, and we're particularly focused on heart regeneration. We hope to address how regeneration is activated upon injury, how cell cycle dynamics are instructed to engage in regeneration and how distinct cell types in the heart coordinate in robust heart regeneration. We hope our work may ultimately help form a basis for the therapeutic repair of human tissues with limited regenerative capacity, like the heart. We also have a collaboration with Dr James Lo's lab at Weill Cornell to compare the differences between fish and mice regarding their regenerative capacities; I think that this kind of comparative study will help move the field forward.

If you could research something other than heart regeneration, what area do you think you would research?

I would say ageing, as it affects everyone; with a better understanding of the ageing process, we could possibly prevent or delay ageing-related diseases and improve the quality of life. Ageing and tissue degeneration are just the opposite of regeneration and rejuvenation, so this is very relevant to my work. I also think embryonic development is a pretty exciting field; gastrulation is the first milestone of life, and how it's regulated is a really fascinating question. We still lack an understanding of this process in fine detail.

You mentioned earlier that you published your first article as a group leader in Development. How did you find your experience of this process?

It was a very pleasant experience; Development is one of my favourite journals. The Editors are scientists, so they know the value of developmental studies and they can make constructive decisions regarding whether a study is impactful or innovative, because they know the field. Also, the Reviewer comments for my paper were very professional and constructive. All these things made the experience very straightforward and pleasant.

You mentioned earlier that you are on Twitter. What are your thoughts on social media for scientists?

I think social media, and particularly Twitter, is a wonderful platform for communicating new discoveries and publications. Often, I'll first learn about a paper or preprint on Twitter. It's also a great place to advertise our work and post about my papers and open positions. After I've advertised open positions in the lab on Twitter, I receive many applications within days. I have also made new friends on Twitter; when I saw an exciting study, I followed the person, I retweeted their post, they followed me back and then we had further conversations. Social media makes communication much easier.

Finally, is there anything Development readers would be surprised to learn about you?

Well, I'm not sure if it is surprising, but as I told you, I liked stargazing when I was young and I love astronomy. I'm particularly interested in astrophotography. When I was in elementary school, I made a telescope from eyeglasses, and I looked at the moons of Jupiter and rings of Saturn. I did a lot of stargazing when I was young, and I wished to become an astronomer when I grew up. But I decided to keep that as a hobby, and now I have three telescopes in my apartment in New York City, although New York City is not an ideal place for stargazing, and not so good for astrophotography. So, I hope I will have more free time to go outside to do astrophotography again.