Lessons Learned - April 2025

I would like to express my gratitude to the NAVBO Education Committee for this opportunity to share my experiences as a junior independent PI. Science is a difficult but rewarding path and never has there been so much uncertainty in this worthy pursuit. During these uncertain times, I welcome the opportunity to reflect upon lessons learned, and most importantly to give thanks to those who lend me their friendship and support throughout this critical period. 

My name is Paul Cheng, and I am an Assistant Professor at Stanford University School of Medicine. I received undergraduate degrees at MIT, followed by MD/PhD at UCSF. I completed my PhD in the Deepak Srivastava lab at UCSF/Gladstone, studying regulation of cardiac progenitor cells during development. I completed an internal medicine residency, cardiology fellowship at Stanford, and postdoctoral training in the Thomas Quertermous lab focusing on genetics of atherosclerosis. 

The overarching focus of my lab is to leverage developmental biology approaches and human genetics to understand pathological cellular transitions in vascular diseases. I am blessed with a wonderful group of talented individuals who took a brave leap of faith to join the Cheng lab, as we probe the edges of human knowledge in vascular diseases. 
Here are a few critical lessons that I failed to truly appreciate until I started my own lab:  

Find your friends and community: The transition from postdoc to PI is often marked by an abrupt increase in the amount of time you seem to spend in isolation on your science, grants, experiments, and papers. Sharing struggles with colleagues and friends locally and nationally to troubleshoot common issues and normalize previously unappreciated hurdles can tremendously help. Through wonderful opportunities available via NAVBO, Vascular Discovery, and various conferences and committees, I have fortunately befriended many wonderful new colleagues and collaborators to discuss new ideas, share the joy of each other’s successes, and bond over the absurd comments by “Reviewer 2.” At my home institution,  I am also blessed with a group of like-minded young scientists, who are excited and willing to provide critical feedback to grants and papers, and commiserate over late-night tea and snacks before pending R01 deadlines. Although I found a community of wonderful colleagues and friends, in retrospect, I underestimated the importance of this factor when considering different potential faculty positions. 

Attitude over aptitude, rigor over refined: Many of my mentors have told me that the most critical decisions for the PI of a new lab are the first few hires. I wanted my lab to be an open, collaborative environment where people help each other and willing to provide constructive criticism of each other’s work. However, this can only be accomplished by consciously molding the culture of the lab, starting with whom you choose to hire. A collaborative lab where members are comfortable with each other lowers the barrier for constructive feedback on each others’ projects and create a synergy of skillsets and ideas in more ways than I could have imagined. At the beginning of a lab, sometimes there is pressure to grow and hire to start exploring all the exciting ideas. Be conscientious about who you hire and wait for the right candidate to fit each potential project. 

Be an optimist and a cheerleader: Being a scientist often means being the harshest critic of your own work, but that attitude needs adjustment as the PI of an expanding team. Science is hard, and the path to good science is full of disproven hypotheses. If you can trust your team members to be cautious and rigorous, it is your job to be the ultimate cheerleader for your team members. We all remember those sad days when we presented negative data to our mentors and lead them to be equally disappointed. With every critical evaluation of negative data, it is important as a PI to help find the silver lining. It is important to normalize negative data, especially if it disproves a hopeful hypothesis.  

Novel tools are never a bad investment -- make them and share them: Unique reagents are often costly investments, and sometimes carry higher risk of failures. Scientific questions frequently lie on two critical axes: (1) how interesting a question is, and (2) how difficult it is to answer said question. While the first axis can rarely be changed (aside from viral shifts in public opinion or unexpected alterations in funding priorities), we can potentially transform the second axis by making new tools that allow answering a question to be easier. Starting a lab is a great time to take the risk and invest in making tools that may simplify your path to many questions you wish to pursue. I was fortunate enough to generate some unique reagents that helped our group answer some outstanding questions in vascular biology. Furthermore, tools you find useful may be helpful for many others! By sharing tools with colleagues in the field, I have gained valuable mentorship and developed numerous new collaborations. I remember thinking long and hard about whether it is worth the risk to invest time and resources into creating new tools, but in retrospect it has paid off more than I could have imagined. 

Identify role models and mentors and consciously learn their ways: There are hundreds of different ways to run a successful lab, but there are common patterns and approaches. As a trainee, I focused on the scientific projects at hand and never spent time considering “why” my mentors’ labs were so successful. But even now, more than a decade later, I still have epiphanies over golden pieces of advice provided by my PhD mentors about running a lab that I never quite appreciated back then. I regret not spending more time asking my mentors about the details of their philosophies and approaches to running a lab. I was fortunate enough to be surrounded by many successful scientists during my PhD and post-doc training, including many who now run successful labs. I find myself emulating many aspects of each of their paths and approaches. 

Don’t lose sight of your passion: One of the best aspect about running your own lab is the academic freedom to chase what you find interesting. Complete autonomy without guard-rails is both jarring and exciting. Beginning your own lab can be difficult, and papers and grants suddenly face more barriers than during your training days. There are temptations to bend your science towards certain hot topics of the day. I myself have been tempted and jumped on the scientific bandwagon a few times. Maybe I am biased by the failure of these attempts, but these often prove to be unwanted distractions. You only have 24 hours in a day. Chasing the big questions that motivated you to start your lab will always be a better investment of your time. While you cannot change the opinions of certain reviewers, good science will always lead to interesting discoveries. Let your passion be the lab’s compass. 

Apply to MORE grants: The best kept open secret from trainees seems to be how many grants applications are submitted by many PIs. To paraphrase Malcolm Gladwell, you don’t need to be the smartest to be successful, but you just need to be smart enough, and put in the 10,000 hours needed to become an expert in your job. One of the main jobs of a PI is to write grants. While we all have done more than 10,000 hours in lab, no one spends an equivalent amount of time writing grants during our training. Sure, we all know people who are successful at every grant that they have ever applied to. However, my survey of many successful young PIs has found that the majority of PIs spend their first few years applying to more grants than I ever imagined as a post doc. Many PI’s apply to more than 10-15 grants annually during their first few years. Grant writing is a skill that comes naturally to some, but for most (like myself), it improves with dedicated practice. I leveraged many grant feedback mechanisms at our institution for early career PIs to obtain feedback on my writing. Writing and receiving reviews with critical anonymous feedback on both the writing and content often cannot be obtained in person from those we know well. 

Treasure your health: Most important of all, amid all the stress and distractions, it is easy to stretch yourself too thin during transitions. It’s important to keep in mind that there is nothing more important than your health, both mentally and physically! Remember to schedule quality time with your friends and family and always try to rest and exercise. It is so easy to lose sight of the bigger picture and deprioritize your own health among competing priorities, but you can’t run your lab if you are not healthy!