Pathway to Independence – an interview with Leah Greenspan

Let's start from the beginning. When did you first become interested in science? Have you always wanted to become a scientist?

I was really interested in science growing up. I remember my parents bought these Time-Life books on astronomy and human anatomy for my brothers, but I loved them. I would make lesson plans and teach them to my stuffed animals. I think that really showed that I was drawn to science growing up. I grew up on Long Island, New York, and we would always do field trips into the city. My favourite trip was to the Museum of Natural History, with dinosaurs and the planetarium. We also went to the New York Hall of Science with all the interactive science activities. My parents were interested in science as well, so I think they really helped foster that interest in me.

You worked in a few labs before your PhD. How did that experience shape you?

In my genetics class during undergrad, we did this comprehensive Drosophila lab where we set up many crosses and learned how to map different genetic traits. From this experience, I got really into genetics and what you can learn from flies, so I joined an evolutionary biology lab and worked with flies for about two years. After I graduated from college, I wasn't sure if I wanted to attend graduate school or medical school. I ended up becoming a research technician at Memorial Sloan Kettering Cancer Center in New York City, where I joined Jennifer Zallen's lab, which was a developmental biology lab. I ended up loving many aspects of developmental biology. I learned how to use the confocal microscope and did a lot of immunostaining and live imaging, and seeing the fluorescent proteins under the microscope blew my mind. Through interacting with grad students and postdocs, I learned more about the academic trajectory. That helped convince me that I did want to go to grad school. I ended up working in Jennifer's lab for about three and a half years. I didn't start grad school until my mid-twenties, but by then I was very certain that academia was the path I wanted. My experience as a research technician really helped me figure out what I wanted to do as a career.

You went on to do your PhD with Erika Matunis at Johns Hopkins University. What did you work on?

I was interested in plasticity and regeneration so that drew me to Erika Matunis’ lab. During my PhD, I studied the Drosophila testis stem cell niche. I was researching what happens to the tissue after injury and how plastic different stem cells could be. In the testes, the niche cells are called hub cells and what I found is that the hub cells can turn into the somatic stem cells of the testis upon injury and upon knockdown of the proliferation inhibitor Retinoblastoma. Even though hub cells were thought to be terminally differentiated cells, my work suggests that they are quite plastic.

What made you decide to join Brant Weinstein's lab for your postdoc and switch from working with Drosophila to zebrafish?

I knew that after three fly labs, it would be advantageous for me to change model organisms, given that grant reviewers usually like to see one's learning potential. I love microscopy and live imaging, so zebrafish seemed like a great fit, because I can do live imaging to see what's going on inside the zebrafish and how the cells are interacting with each other. As for the research topic, I was looking at labs where I could work on regeneration. Brant, my current PI, is great about listening to my ideas and working with me to come up with a project. I started my postdoc by focusing on how blood vessels are important for tissue repair after an injury.

People usually recommend that you either switch model organisms or tissue – I switched both, which was challenging. I knew by switching that I needed a very supportive and helpful lab, as I went from knowing everything about Drosophila to knowing nothing about zebrafish, even just the husbandry, and how long experiments will take. I am very fortunate that everyone in my current lab is so generous and willing to help and answer my questions. This really helped with my transition to zebrafish and to a new tissue.

What are you currently working on?

I am currently studying cutaneous wound healing and have developed an injury system to make a reproducible cutaneous wound in the zebrafish. As zebrafish are known to be good at regenerating different tissues after injury and are amenable to live imaging, they have been an excellent model organism to study the different stages of wound healing in real-time. This has led me to explore many different aspects that I never thought I would be studying such as immune cell recruitment. But that's how science works – it takes you to interesting and exciting places. I have been looking at how many of the different cell types such as skin, immune cells, and blood and lymphatic vessels regrow and repair after cutaneous injury. I am hoping to look more into how these cell types coordinate with each other – perhaps imaging multiple cell types at the same time after injury and following how they interact with each other.

How did you hear about Development's Pathway to Independence Programme and why did you decide to apply?

I saw it posted on Twitter and thought it would be interesting. I am starting to apply for jobs now, so it seemed to fit with my timeline. I am always in the mindset to apply for things that I think will benefit me, so this programme seemed like a good fit.

What do you hope to get out of the programme?

I really like the idea of having a cohort that is going through the same thing and I can share experiences with. I also like the idea of having an editor as a mentor. I'm hoping when I start my applications I'll reach out to my mentor, Jim Wells, a bit more so I can get some feedback. I think getting feedback from different people is very helpful, because everyone has different experiences. Obviously, as someone going on the job market, doing more networking and hopefully getting a little more exposure will be useful to get my name out there more.

Where are you in the process of securing an independent position and what has your experience been so far?

In the US, a lot of the jobs get posted starting in the summer and into the fall, then the interview process starts. Once I get my paper revisions out of the way, I plan to start looking a bit more carefully and really focusing on job applications and making spreadsheets of where I want to apply, when everything is due and what the requirements are. Even though I haven't started applying yet, I have written a teaching statement, a diversity statement and a two-page research statement. I know that the requirements are different depending on the application, but at least I have some of the documents ready to go.

What are the factors you consider when you look for an independent position?

For me, the deciding factor is the environment and the support. I want to join a department that is going to be supportive. As a new PI, it is important to have colleagues who want you to be successful. I am going to keep an open mind, and I'm happy to apply to different departments at different locations. I know it is different from country to country but, in the US, if you are at an undergraduate university, you tend to do more teaching and your salary is more guaranteed, versus in a medical institute where it all has to come from your own grants, but you don't do as much teaching. I prefer more teaching and more security, ideally, but I don't think I can be picky. It is competitive so I am happy to cast a wide net.

What excites you most about becoming an independent group leader?

I am excited that I will get to test out all my ideas and all the questions I have in the field. As a PI, you are running the ship, so you get to decide which projects students work on and which direction you want to go in. I like the creativity and coming up with interesting ways to answer complex questions in biology.

I also enjoy mentoring students. Showing them how fun science can be is extremely rewarding. This is true especially for younger mentees, because their experience in high school labs and college science labs does not compare with working in a real research lab. It is quite enjoyable when students get to see all the cool techniques and find out how fun science can be.

And conversely, what do you think will be the most challenging aspect of being a PI and how will you prepare for it?

As scientists, we are not trained on how to run a lab, so that is always a little bit tricky when you transition and, suddenly, you have a very large budget you need to figure out how to use. Also, as much as I love mentoring, I think it will be challenging dealing with conflicts. I have taken a management bootcamp that the National Institutes of Health (NIH) Office of Intramural Training and Education offered, so that was nice to learn some strategies that will be beneficial when hiring for my new lab. Obviously, the idea of having to constantly write grants and provide your own funding is challenging, so I've been doing my best to write as many grants as possible throughout my grad school and postdoc just to practice that skill set. But it's a little nerve racking knowing that you could just run out of money. I know there will be a lot of challenges, but it's something that I have wanted for a long time, so I think it's worth a try.

What kind of research questions are you planning to address in your group?

As mentioned before, I am studying cutaneous wound healing and I have established this zebrafish model where we can study the different stages of wound healing. When I start my own group, I am interested in doing a couple of things. One is to look at how the stages of wound healing are affected in different conditions such as aging and diabetes. It is known that the elderly population, as well as those with diabetes, have a higher prevalence of chronic open wounds. Zebrafish are a great model for us to ask why these wounds are not healing. With live imaging and the ability to look at all the different cell types, we can start to understand what is going wrong in those chronic open wound conditions.

One reason that some cutaneous wounds don't heal properly is because there is a delay in their vessel regrowth. Therefore, another area I'm interested in focusing on in my own lab is using molecular tools to ascertain the changes in endothelial molecular signatures at different time points during healing as well as during different disease conditions to find out what's going on in the vasculature specifically.

In your opinion, what are some of the most exciting advances in your field?

What I think is really exciting is the microscopy and the way that we can visualize wound healing in a living animal over time. In zebrafish, we have all these tools that not only allow us to label different cell types, but to look at signalling dynamics during healing. There are also sensors for metabolism and for mechanical forces. With all these different fluorescent reporters and the recent advances in high resolution microscopy, we can start combining tools to understand how different aspects are coordinated. I think the future is going to be understanding how everything works together to repair a tissue after an injury in normal and in disease conditions.

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

I think mentorship is extremely important. Without people to help and support you, it's very difficult to keep moving along this challenging trajectory that has many highs and lows. A good supportive mentor can help train you to think like a scientist, give advice on how to write and edit and be there if experiments fail and give ideas. It is also important to have someone that's going to introduce you to people. I have been fortunate to have been in labs with PIs who are very, very supportive and approachable. I feel like I can go to them whenever I need to. It's been interesting for me to see how different PIs run their labs. I get to pick and choose what I like from each of them and hopefully apply what I learn from them when I start my own research group.

I think it's also good to have mentors who are not your PI, whether it's a committee member or your peers. I've been fortunate to have peers who are willing to talk about science and our projects informally. Even previous lab members who have gone on to start their own labs, they are willing to share their grant proposals, give me advice and read over my application. I think having people to turn to is important in this career.

I hope I can be a good mentor for my trainees as well. I'm always willing to edit their documents, talk about experiments and help them think through things. We have a lot of summer student programmes and postbac programmes at the NIH and I think the NIH has done a good job to ensure we have a diverse pool of students in the lab. I love having students who haven't had any lab experience before coming to the lab and get to truly enjoy science the way we do every day.

Can you talk more about the outreach work you have done throughout your career?

When I was in grad school at Johns Hopkins, I started a programme where local high school students from Baltimore would come visit our university and participate in a day of hands-on experiments, including crystallizing a protein and simulating how epidemics spread. Throughout grad school, I always volunteered to demo for the many students coming to the lab, from elementary, middle school to med school students. We would invite them into our lab and teach them about fly genetics. At the NIH where I'm currently based, they don't have those programmes, because it's not a university. I do miss these outreach activities. Hopefully, I'll get to do more when I have my own lab.

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

It's not as important that I'm in an academic setting, it's more that I want to run my own lab and have control over what I study. But if an opportunity was to arise, I'm not opposed to startups or industry, I just don't think they fit with what I truly want to do. I have a lot of ideas, and I want to have the freedom to explore them. I also want to be mentoring and training the next generation of scientists, which I think is fun and exciting. I want the more junior students to be able to speak up in meetings and not be afraid to ask questions. I like that in academia, everyone can learn from each other, no matter your level of training.

What do you like to do outside of the lab?

I enjoy hiking and travelling. I have done treks in Peru, including hiking the Inca Trail to Machu Picchu. I've gone backpacking in Denali National Park in Alaska, where there is no set trail, you just have a compass and a map. I have also rappelled down waterfalls in the Himalayan foothills in Nepal, and taken part in more extreme activities like that.

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