Advice for the Next Generation: Kelley Yan

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Q&A Advice for the Next Generation: Kelley Yan Pursuing an academic investigator position is challenging, and every scientist’s journey is unique. In this interview series, Cell Stem Cell chats with six newly established professors on how they built a competitive application and their advice for trainees interested in this career path. Here, we seek Dr. Kelley Yan’s insights. Tell us a little bit about your career path and your lab’s research interests. I am a physician-scientist and my lab uses multidisciplinary approaches to study intestinal stem cell (ISC) biology in health and disease. My career was not achieved by design, but rather it is simply the result of pieces that fell together as I matured in my education and training. My interest in science was initially aroused by an undergraduate chemistry course. My professor invited me to do summer research with him and I was hooked. I enjoyed the logic and deductive reasoning of chemistry in the classroom. But I was really drawn to the creative aspects of research and to the buzz I felt when I occasionally stumbled upon something on my own (even if I found out later that someone else had already discovered it). I knew I wanted to do research on important topics but didn’t know enough to ask the right questions. So I entered the M.D./Ph.D. combined degree program at Mount Sinai to learn about medicine and biology. I completed Ph.D. studies in structural biology using NMR spectroscopy to examine 3D protein structure. After graduation, I chose to train in internal medicine and specialize in gastroenterology at Stanford based on my interest in GI patients and their diseases, without thinking much about how my clinical specialty and future research career would ultimately fit together. Rather fortuitously, the first molecular markers of ISCs and new intestinal organoid technology were described while I was doing my clinical training. At the time, Calvin Kuo’s lab at Stanford was developing methods for growing intestinal organoids. So I joined his lab as a postdoc to learn organoid technology and mouse genetics and began working in the field of ISC biology. Returning to the bench after a 5+ year hiatus of clinical work was challenging, especially in a completely different field! I feel fortunate that I had the opportunity to explore, discover, and follow my passions. 852 Cell Stem Cell 24, June 6, 2019

you. Not because you think they will lead to big papers, but because you have a passion for the work itself. You must get excited by the questions that the work is addressing. When you are alone in the lab on a Saturday evening taking care of your cells, this is what will ultimately sustain you. It will be what gets you up in the morning excited to come into work. This will also be what sustains you as a PI. Postdocs (and graduate students) should always take charge of their projects intellectually. Not only should they execute the experiments, but importantly, they should try to become the intellectual drivers. Kelley Yan Columbia University

This is a luxury that was afforded to me by my mentors and supported through a CIRM fellowship, as well as career development awards from NIH and Burroughs Wellcome Fund that enabled me to transition to an independent faculty position at Columbia University in the fall of 2016. These diverse training experiences shape the way that I ask and answer questions. My lab uses genetics, organoids, biochemistry, and structural biology to understand and manipulate ISCs and their niche for therapeutic benefit. I also practice clinical gastroenterology 1 day per week. I absolutely love my career but would never have been able to imagine doing this 10 or 20 years ago! Do you have any suggestions for how postdocs should approach their projects as they consider their desired research directions as a PI? There is a lot of pressure to publish highimpact work given the current competitive environment. However, publications can be difficult to gauge or predict when you are just starting a project as a postdoc. The best piece of advice I can give is that you should pursue projects that excite

What do you wish you knew in graduate school or beginning your postdoc? How can trainees invest their time to become more competitive for an academic position? I wish I had spent less time worrying about my perceived failures and inadequacies. Criticism, rejection, and failure go handin-hand with a scientific career. We need to develop the means to cope with these setbacks constructively, and the sooner this happens, the better. In my opinion, the best investment in your future career is to spend a lot of time on introspection and learning as much as possible from these failures. Sometimes being too lucky and successful early on can be the worst thing that can happen to a young trainee. The times I have not gotten the outcome I desired were the times when I learned the most about myself and my abilities, and they ultimately changed the way I went about my life and career. At the beginning of graduate school, I was overly concerned about the practical aspects of conducting the experiments themselves. From the beginning, trainees should pay more attention to the big picture. Pay more attention to the questions you are asking, why you are doing certain experiments, and how you are interpreting the data.

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Q&A In terms of practical wet-lab experience, I think most techniques and practical skills can be learned. Science is a process of evolution, and nobody can expect to sustain a long and successful career with only a few methods and techniques. However, since I started my training, I think science has experienced a large shift where computational analysis is at a premium. The bottleneck in science used to be data generation, and now it is data analysis. As bench scientists, we will increasingly rely on collaboration with our computational colleagues. Scientists in training would be wise to at least familiarize yourself with these approaches, even if you will likely still rely on collaboration with experts. The scientists who can effectively bridge the divide between data generation and data analysis will be at an advantage. Another piece of practical advice is to hone grant writing skills early in your career. It is essential for academics to learn effective grantsmanship early and to improve those skills over time. Although in graduate school, I had to write a grant proposal as part of my qualification exams, I never understood the true purpose of this skill. I think that learning to write good grants also instills a framework on the actual scientific process itself. Your thinking about hypotheses and experiments is enhanced through the process of writing a proposal. Do you have any strategies for effective networking? I was always told to meet and interact with as many people as you can. This was always difficult for me because I am shy by nature. So I attended meetings and took every opportunity to present my work in front of others. Importantly, always be courteous to whomever you encounter, no matter who it is. That graduate student who asked all the questions at your poster may become your boss one day. The worst thing is not that people don’t remember you. The worst thing is that people remember you for being less than kind. Do you have any suggestions for how trainees can feel empowered to drive their careers forward in the event of setbacks? Do you have any personal stories that you can share? Setbacks, whether scientific or personal, are always a part of this career and a part of life. Personally, the biggest chal-

lenge I had to overcome was starting a family in the midst of trying to establish my career. People always say that there’s never a good time to have children. It was difficult to fathom the idea of raising children while I was in school or during my residency training. Initially, I simply didn’t want to have them, but I gradually changed my mind as I got married and got older. By the time I was ready to take the plunge, I was already settled into my postdoc position and well into my thirties, and then was shocked to find that I had difficulty conceiving. It should not have been shocking since it is well known that a woman’s fertility goes into steep decline in her thirties. But somehow this information was lost upon me because friends, colleagues, and even celebrities in the news are having children in their late thirties and into their forties. My husband (also a postdoc at the time) and I went through years of struggle before we finally conceived our triplets in 2014. We were struggling financially and both moonlighting at second jobs to pay for the expensive treatments. Aside from family and a few close friends facing similar challenges, we did not share any of our struggles with our mentors or colleagues. While we were suffering emotionally and financially, the view from the outside was probably that things were going well. Despite the fact that I am a private person, I share this story now because I think it’s important for the next generation to hear, especially the young women who will spend many of their childbearing years in training. Keep in mind the distinct biological differences between men and women. Make informed and deliberate choices about how to spend those years. It’s okay to change your mind as you progress in your education and training. Don’t let things happen passively. Always know what your priorities are. I think that many people feel that you have to give up your career ambitions in order to start a family or vice versa. Unfortunately, it’s true that starting a family usually entails making sacrifices. During those dark times, I often questioned my career ambitions and would have traded any degree or professional accomplishment to have a child. This didn’t make me any less committed to a scientific career but rather it only reflects the fact that I am human. In retrospect, during

the years of doctors’ appointments, fertility treatments, high-risk triplet pregnancy, and then raising young triplets, I was also arguably at my most productive in the lab. During this time, I generated data at the bench, published papers, received grants, obtained a faculty position, and started my own lab. This is not to say life was easy during this time, but going through fertility treatments and having triplets certainly didn’t make a scientific career impossible. Getting through difficult times is empowering because it provides you with the confidence to persevere in the face of challenges. I am a firm believer that we are shaped much more by how we deal with our failures, shortcomings, and struggles than by the successes that come easily. I am really fortunate that I had access and means to great medical care. Importantly, we have really great support with childcare. From my perspective now, my struggles to have my children reaffirmed for me the purpose of the work we do as scientists and physicians, having been the recipient of science, medicine, and technology myself. In this way, I am glad that I went through difficult times because it enables me to have greater appreciation for the life I lead today. I’m really heartbroken for those who don’t have the means to get medical treatment or don’t have good support in caring for their kids.

What type of teaching or mentorship experiences should trainees seek to prepare themselves for academic teaching requirements in PI positions? Teaching is an inherent part of being a successful scientist. Even if scientists do not formally teach in their careers, they are constantly presenting their work and teaching informally. The skill in being able to clearly present your science is very similar to the skill it takes to present a topic to a group of graduate students. I don’t think there is anything special that a trainee should do to prepare for teaching. Work on being a great presenter of your science at group meetings, the local seminar, or national meetings. By doing that, you are becoming a better teacher. After all, as I once heard from a prominent dean at a major academic research center. ‘‘Good teaching Cell Stem Cell 24, June 6, 2019 853

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Q&A evaluations? That’s great. But it’s not going to get you tenure!’’ In my own career, I have worked hard to improve my ability to teach and give talks. A lot of my anxiety about teaching and giving talks was simply due to my own perception of these activities as performances. I became more comfortable by simply reframing these activities in my own mind as acts of sharing rather than performing. Teaching is really about sharing with the audience and taking the time to tailor your content to make sure that the audience gets the most out of it rather than simply indulging yourself as the speaker. Have you started any de novo collaborations as a new PI, and do you have any advice for how new PIs can set up and maintain a good collaboration? The best collaborations arise organically and are always mutually beneficial. Collaborations can’t happen for the sake of collaboration. With the increased emphasis on collaborative projects on the part of the NIH and other funding agencies, this can be lost. I’ve been fortunate to have colleagues and mentors that are happy to help me and even go out of the way for me, but this always has a limit. So always keep this in mind. As with many relationships, the more you put in on your end, the more you will get out of it. Don’t think about how much you can benefit from a collaboration without considering your collaborator’s perspective. I always approach a collaboration by trying to offer my potential collaborator as much or even

more benefit than I would reap. Almost everyone will appreciate this and work harder to help you accomplish your goals. Do you have any advice for establishing a good work/life balance as a trainee and now as an early stage PI? Academic careers offer surprising flexibility and are very compatible with good work/life balance. For me, I am very comfortable with compartmentalizing my life. I try to keep regular regimented work hours and come to work with a specific agenda to accomplish by the end of the day, week, or month. I set clear goals and don’t go home until I reach my goal. Once I go home, I try to avoid working or spending time on my computer until I return to work. Efficiency is really critical. After the birth of my children, my efficiency has risen dramatically! This usually means that I spend less time perseverating on minor details sometimes just to finish something. Now I focus on completing my tasks just to get them done, even if they are not 100% perfect. Be comfortable with less than perfection at home and at work. Learning to delegate tasks effectively is also important at work and at home. Some tasks are better done by others. I don’t feel the need to shuttle my kids to pre-school, cook all meals myself, or clean my house every day. Either I pay someone else to do these tasks or accept the fact that my house and office are always less than completely tidy. I am fortunate that my family is supportive of my career. My husband is also a physician-scientist and runs his own

lab at Columbia. He will often offload some of my home responsibilities when I travel or have important deadlines. Outside of work, my free time is spent with my children and family. The kids are still at an age where they have destructive tendencies and you can’t really leave them alone. Most days I try to have breakfast and dinner with them, even if that means that they eat dinner late. I wouldn’t have it any other way. Before we started our family, I enjoyed traveling, cooking, dining out, wine, movies, yoga, and skiing. I’m slowly working my way back to some of those things. I feel that it is really important to have interests outside the lab. Certainly, bench science requires a lot of time, focused attention, and hard work. But science is also ultimately a creative process, and sometimes walking away from the bench can actually bring you closer to your goals. When things are not going well at work, then I can get stimulated and rejuvenated at home. This provides a much needed balance. Although some view work and family as competing interests for your attention and time, I find that they are very much synergistic and complementary. Raising children has enhanced my career and made me a better PI/mentor. I realize now that my biggest contribution is not necessarily what I accomplish with my own hands, but the legacy that I leave behind in my trainees. Rather than detracting from my career ambitions, my children have increased my desire to be successful in my career so that I can set an example for them. https://doi.org/10.1016/j.stem.2019.05.004

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