An interview with Mayssa Mokalled Free

Let's start at the beginning – could you take us back to the first moment that you became interested in science?

I'm from a small village in South Lebanon and I grew up interested in understanding how things work, which translated into a general interest in STEM (science, technology, engineering and mathematics). With little exposure to biological research, I was originally interested in engineering. I thought engineering would be the path to understanding how things are built. But, in my last year of high school, I discovered that nature is the master of all engineers and this led me to shift my interests to biology and biomedical research. It's been a fun adventure.

Was it at that point you decided to have a career in biology?

I was accepted at the American University of Beirut to study engineering. Since my interests had shifted away from engineering by the time I started college, I decided to major in biology instead. In a country like Lebanon, you don't grow up hearing about research and careers in biomedical research. When I got to do my first experiment as an undergraduate, which was a western blot, a whole world opened up! I think loading that first gel was the defining moment when I realised I wanted to be a scientist and I still enjoy western blots because of that.

What attracted you to go to Eric Olson's lab at the University of Texas (UT) Southwestern, USA, for your PhD and what was it like moving from Lebanon to the States?

I had great mentoring in Lebanon, but very limited resources. I was exposed to all the great research happening in the rest of the world only on paper and I always wondered how some of those experiments were actually performed. So, I decided to go to the USA to learn how high-impact research papers were made. With a lot of help from my mentors, I started applying for PhD positions. At that point, and this will tell you how old I am, applications were all on paper and there were no interviews, not even Skype interviews. I received responses in paper envelopes – a lot of them with rejections – and some with acceptances. I emailed Eric from Beirut and expressed my interest in carrying out a rotation project in his lab and he replied within five minutes, which I thought was amazing!

When I first got to Dallas (Texas, USA), it was all different and foreign to me. Meeting Eric was a bit intimidating, but it reminded me why I was there. He asked me about my experience with mouse work and I didn't have any. He asked me if I had any family in the States and I didn't have any. Then he told me not to worry because the lab will teach me everything I need and would become my family in Dallas. I decided to do my PhD there and I was eager to learn it all!

Moving to the USA turned out to be an amazing experience that fulfilled a lifelong dream. It shaped the person and the scientist that I am. When you go through a change like this, at least for me, the first thing you do is try to hold on to your identity. But the international and diverse world of research broadens your perspectives. I quickly learned that by living abroad you gain more than you lose – you just have to be open to learning and enjoying the experience. It takes only a few people to shape your career and to give you that push when you need it, and Eric did that for me.

What was your PhD project?

My PhD studies focused on deciphering mechanisms by which cells sense and react to their extracellular environment. I specifically studied the myocardin-related transcription factors (MRTFs) in the contexts of brain development (Mokalled et al., 2010), heart development (Mokalled et al., 2015) and skeletal muscle regeneration (Mokalled et al., 2012) in mice. MRTFs comprise a family of transcriptional co-activators, which control gene transcription in response to changes in cytoskeletal dynamics. This family of genes turned out to be fundamental for every aspect of developmental biology! I am particularly fortunate that the first of these discoveries was published in Development.

What was it about regeneration that really appealed to you and what did you work on during your postdoc in Ken Poss's lab at Duke University (North Carolina, USA)?

I'm a developmental biologist at heart and, to me, regeneration is development with an extra layer of complexity. My interest is in understanding how tissues re-form and regain function after injury in an adult organism. I became interested in muscle regeneration in Eric's lab. Skeletal muscle is a highly regenerative system in mammals, where self-repair is supported by a stem cell population that proliferates and differentiates into new muscle fibres after injury. In addition, one can't help but appreciate that regenerative capacity is unevenly distributed among tissues and organisms. The wide distribution of regenerative capacity led me to think about different systems that may be more difficult to regenerate, but for which the evolutionary diversity in regenerative capacity is more pronounced. This is how I decided to shift my focus to the nervous system for my postdoctoral work.

At the time, the Poss lab had been studying tissue regeneration in the zebrafish heart and fin, but Ken supported my plan to study the spinal cord and that was the place where I wanted to be. Zebrafish have a remarkable capacity for spinal cord regeneration; they can reverse paralysis and regain sensory and motor functions within 6-8 weeks of injury. I got to work and it was thrilling to witness that regenerative capacity first-hand. Studying spinal cord regeneration in a lab that studies heart and fin came with its own challenges, especially when it came to funding; there were many grant rejections, but I could see the power in the system and I knew there were discoveries to be made. It was just a matter of time before these discoveries emerged and it was rewarding to overcome those challenges with Ken's support.

It sounds like you had a lot of independence to start new projects in a lab beyond their primary research focus, and got experience in obtaining your own grants, etc. Do you think that was helpful when you started looking for independent positions?

Absolutely. Gaining independence is a gradual process. My first steps toward independence were in Eric's lab, where I diverged from muscle work to study brain development. With every small step towards independence, you gain the confidence and credibility to tackle the next one. It was in Ken's lab that I became fully prepared for an independent career. I would encourage young scientists to be flexible and to seek independence as scientific opportunities arise. It is equally important to seek help if you hit a wall on your path toward independence.

What was it like for you when you became a group leader and why did you decide to go to Washington University (Missouri, USA) to start your lab?

The experience of starting my own lab was phenomenal. It's probably the most fun I've ever had in science. It's a privilege to pursue my passion as a job and to begin to answer questions that I'm most interested in. My science is interdisciplinary: at the intersection of zebrafish genetics, neuroscience, evolutionary biology and developmental biology. My goal is to translate fundamental principles of tissue regeneration into clinical applications. When I was looking for an institution that could provide the support, resources and communities for these different disciplines, WashU (Washington University) was an obvious choice. My lab is part of a great zebrafish community that benefits from a world-class zebrafish facility. We are in the Department of Developmental Biology, with open interactions with neuroscientists in the Hope Center for Neurological Disorders, with regeneration biologists in the Center of Regenerative Medicine, and with clinician scientists across campus. In modern-day science, it's limiting to tackle one question from one perspective and with a limited set of expertise. Being in an environment that supports collaborative approaches like WashU is extremely valuable.

How well do you think that these different fields complement each other and do you think it's important to be interdisciplinary?

There are two schools of thought here. The first tells young scientists to train in one field and become the expert in it. I think that's valuable, but my career path led me to accumulate diverse experiences in different fields, which is the second school of thought. As I mentioned, regeneration is the context in which I like to address developmental questions. It's difficult to think about regeneration and regenerative capacity without stumbling upon the evolutionary aspect of that capacity. Then, of course, being the interdisciplinarity research lab that we are, we cannot ignore the clinical applications of our tissue regeneration research to manipulate injury or disease outcomes in poorly regenerative systems. I believe having broad experiences allows us to tackle these biological questions from multiple angles without being limited in scope. It also gives us the flexibility to pursue new directions as they arise. I think interdisciplinary researchers are in a unique position to serve as ambassadors between fields that may not necessarily interact with each other. For example, I get to interact with scientific communities interested in fundamental or clinical aspects of spinal cord injury. I hope I can contribute to bridging these disciplines together because, ultimately, this is where the broader impact in the field is going to happen.

Could you summarise the current themes of your research?

We're interested in dissecting and manipulating fundamental mechanisms of neural regeneration. Our goal is to dissect the cell identities and molecular mechanisms that direct innate spinal cord repair in zebrafish, to understand the basis of differential regenerative capacity using comparative approaches between zebrafish and mammals, and to translate our findings from zebrafish to improve neural repair in mammals. Projects in the lab are focused on understanding the potency of the progenitor cells and the role of the immune system during innate spinal cord repair. We have a long-standing interest in zebrafish glial cells, which seem to be exclusively pro-regenerative, whereas mammalian glia have both pro- and anti-regenerative functions. One area that I am particularly excited about is to employ cell reprogramming to engineer zebrafish-like cell identities in human systems. With the knowledge we're accumulating about the identities and the behaviour of the cells that drive regeneration in the fish, and with the advances that have been made in the cell reprogramming field, we have a unique opportunity to engineer glial cells that can be exclusively pro-regenerative in humans or to manipulate the potency of human stem cells to support mammalian regeneration.

The ability to generate collaborations, to keep them going and to really make them fruitful is a valuable skill. Are there any other skills that you would advise young scientists to develop?

How does one become a good leader? By the time you start a lab, you've already gone through years of research experience and project ideas are well-developed for the next 5 years. The scientific basis is solid by that time, but the new challenges junior faculty face are building a coherent team, supporting team members and securing funding. To be better prepared for these challenges, I would encourage trainees to mentor junior members in their labs and practice grant writing during their predoctoral and postdoctoral training. Apply for grants, irrespective of the outcome. In my case, having had my share of rejections as a trainee helped me secure funds relatively quickly for my lab.

You've already mentioned how influential your mentors have been during your career. What approaches have you taken to mentoring others?

Being a mentor starts early on in one's career path. One thing I'm particularly passionate about is supporting postdocs in my lab and beyond. Postdocs are in a semi-independent position and often under a lot of pressure in terms of making career choices. There are a lot of questions: Which career path should they take? What are the opportunities outside academia? Can they actually stay in academia if they want to? How to build a competitive portfolio for their next career step? To help with these questions, I serve as the postdoc liaison in the Department of Developmental Biology and in the Center of Regenerative Medicine at WashU. We chat about challenges and opportunities, such as papers, grants, academic faculty positions and industry jobs. Informal mentorship discussions in a relaxed setting, not necessarily with your own formal mentor, can be valuable and enriching.

In 2022, you were awarded the first Rising Star Award from the new International Society for Regenerative Biology (ISRB). What does this achievement mean for you?

Receiving the first Rising Star Award from the ISRB is a great recognition for my lab. My lab was young when the COVID-19 pandemic started, but the team came together and worked hard through these difficult times. I am thrilled and proud of this recognition for the whole team. It's also a huge responsibility – I hope we can live up to this award by continuing to make impactful discoveries and helping to move the field of regenerative biology forward.

What excites you in the field at the moment?

There's a lot of excitement about the ISRB. Scientists studying tissue regeneration have been present in multiple fields and it is exciting to see the field brought together under the ISRB. Personally, I am particularly excited to see how we can apply technological advances and the vast datasets we can collect these days, to better understand nature's secrets in order to resolve injuries and to develop our ability to promote tissue repair across species. I think, in the next few years, we will be able to witness this happening.

Finally, what would Development readers be surprised to learn about you?

I'm an avid cyclist and when I'm not looking at the world through a microscope, I like to discover it on a bike. It helps me clear my head and come back with fresh ideas. To come full circle, cycling allows me to get back to nature, the master engineer. Although we still have a lot to do to understand how the natural world works, it is good to take a break and appreciate its beauty from time to time.