Ya-Chieh Hsu: Running a Candy Shop (Part 2)

See Part 1 to read about Dr. Hsu’s journey from high school research student to principal investigator. In the final portion of our two-part interview, we spoke with Dr. Hsu about the fun and challenges of starting her own lab.

Q: In the past few years, you built a lab from scratch as a new PI at Harvard. What's the biggest challenge of creating a new lab? What was the most rewarding part?

A: Starting a lab is perhaps the most difficult thing I have done so far, but of course it’s also the most rewarding. When I walked into my lab the first day, it was empty! There were no chairs, no trashcans, nothing! You build a lab from there. It made me truly realize how much I’ve taken for granted in the past. At the same time, it was also very exciting to build something from nothing.

I think the biggest challenge lies in finding the right people who are not just great scientists and good people, but are compatible with you and work well with one another. The first group of people set up the tone, helped the lab take off, and also helped me become a better mentor. They need to have an adventurous spirit, and there’s a lot of “togetherness” that you need to help nurture. It took me a long time to find people whom I thought would be a good fit. But it was definitely worth the wait. I'm very happy with the people I have now and take great pride in them. Witnessing their growth is definitely the most rewarding part of this process.

dr. hsu's lab before

Dr. Hsu's lab when it began, in the summer of 2014.

Q: Your lab just published a paper in Genes and Development on how tissues communicate to coordinate their changes. Tell us a bit more about what was so exciting about this finding.

A: It exemplifies our thinking around tissues and organs. It also shows what transit-amplifying cells can do. During the regeneration phase, hair follicles are perhaps the most proliferative tissue in adults. They grow at least 60x longer within a week. How can the neighboring tissues adopt? Is there even sufficient space?

The first group of people set up the tone, helped the lab take off, and also helped me become a better mentor.

dr. hsu's lab today

Dr. Hsu's lab today.

We found that transit-amplifying cells of the regenerating hair follicles secrete Sonic Hedgehog to promote dermal adipocyte precursors to make more adipocytes. The newly produced adipocytes quickly expand the thickness of the skin that creates the space required to accommodate the rapidly downgrowing hair follicles. This shows that a regenerating tissue might employ a regulatory mechanism to make things work around them, rather than just sit there and be passively regulated by the niche.

It also brings up a concern that I did not think of before we conducted this study; tissues are dependent upon one another and there are key cell types, such as the hair follicles’ transit amplifying cells, that connect these interdependencies. When these cell types have problems or are targeted by drugs like chemotherapy agents, many tissues can be affected at the same time. This helps us understand the effects and side effects of drugs in a more comprehensive manner. On the other hand, this realization also brings hope. Within an organ, there seems to be some cell types that are “more equal than others.” To restore or enhance organ functions, you may not need to work on cell types one by one if you find out which types have a broader impact and focus on those.

Q: There's a balance between fostering personal growth and making sure the progress of research in the lab is going at the right pace. How do you balance these two?

A: Everybody is different and every situation is different. Sometimes, all they need are trust and encouragement. Other times, they need someone to push them out of their comfort zone so that they can realize their full potential. It is definitely important to give people time to grow and explore. On the other hand, everyone needs to feel that they are moving forward, and that they are rewarded by making progress towards an important scientific problem. Keeping that balance is something I'm constantly thinking about. How can I be both authoritative and open-minded? When should I use my experience to help, and when should I step aside to let them figure things out?

When should I use my experience to help, and when should I step aside to let them figure things out?

I can’t say I’ve always made the right decision. Like everything else, you learn through experience, and you adjust with different personalities and situations. I am guided by some very simple principles: first, science is about searching for the truth, and my people’s job is to discover what the truth is, not what I like or what I think. My position is to facilitate them on this journey, so that they can achieve amazing things that are sometimes even beyond their own imaginations. They will need me in different ways along the way, and it’s important for me to recognize and adapt. Second, everything I do right now has a long-term consequence. If it is the right thing to encourage for long-term and larger goals, then that’s what we’ll focus on even if the short-term reward may be compromised.

Q: Speaking of the big picture, what are some other key technologies that you think can drive the field of stem cells and regeneration forward?

A: We are very excited by single-cell approaches because they tie into how we think about the complexity of a given tissue and the heterogeneity within tissues. They also build collaboration by bringing in diverse expertise, which I'm always a huge fan of. At the same time, I think that in facing all the wonderful new technologies, there is no substitute for a deep understanding and appreciation of tissues, development, and regeneration processes. Without them, we can’t make sense of the data. Max Delbrück once said, “Don’t do fashionable science.” I think it sounds even more timely and suitable in this era of new technology.