Tête-à-tête with Pei-Hsuan Wu

Get to know another invited speaker to the upcoming 15th NYRA Meeting in Caux (June 17th-18th) through this interview. 

Dr. Pei-Hsuan Wu conducted her Ph.D. research with Richard Carthew at Northwestern University in Evanston (Illinois, U.S.). After receiving her Ph.D. degree in 2013, she joined Phillip Zamore’s laboratory at the RNA Therapeutics Institute at the University of Massachusetts Medical School on the east coast of the U.S., where she stayed from 2013 to 2021 as a postdoctoral associate and, later, as an instructor. Nowadays, supported by PRIMA from the Swiss National Science Foundation, Dr. Wu leads the “Function and mechanism of germline small non-coding RNAs in sperm and embryos” research group at the Université de Genève (UNIGE), in Switzerland, as an Assistant Professor at the Department of Genetic Medicine and Development at UNIGE Faculty of Medicine.

Her research focuses on 1) describing functions and mechanisms of small ncRNAs in spermatogenesis and embryogenesis, 2) deciphering the paternal contribution to the offspring via sperm PIWI-interacting RNAs (piRNAs), and 3) characterizing the function of pachytene piRNAs using CRISPR/Cas9, mouse genetics, and sequencing. Find all details about Dr. Wu’s research at https://www.unige.ch/medecine/gede/en/research-groups/wu-lab/

When and why did you decide to work in the field of reproductive biology?

I first encountered the reproductive field as a Ph.D. student. I worked in Dr. Tereasa Woodruff’s lab at Northwestern University during my “rotation” year, which is a routine process for first-year Ph.D. students in the US, during which you work in different labs before choosing a thesis lab. I worked on female reproduction in this rotation. It was a tough call, but I ended up joining another lab to work on gene silencing by small non-coding RNAs (RNA interference) for my thesis. Years later, my postdoc project serendipitously brought me back to reproduction biology. At the University of Massachusetts Medical School in the US, I worked on PIWI-interacting small RNAs (piRNAs), which are germline-specific small non-coding RNAs with a role in animal fertility. Reproductive biology is fascinating to me because of its implication in species survival and the unique germ cell biology. As a fan of the general topic of gene expression regulation, germ cell biology is a challenging and, therefore, interesting system to work with.

Looking back on your career, how do you feel the fast development of tools for high-fidelity gene edition (such as CRISPR/Cas9 or other variants) has impacted your research? And, more globally, how are they helping (or how can they further help) the study of paternal transmission of epigenetic traits to subsequent generations?

I could not have done my postdoc work without the latest generation of gene editing tools. It changed how we worked with mouse genetics seemingly overnight when in vivo gene editing by CRISPR/Cas9 was first reported at the same time when I started my postdoc. The type of my postdoc work, disrupting multiple non-coding RNA loci in mice would not have been feasible otherwise. CRISPR/Cas will continue to be indispensable for making mouse mutants to study the paternal transmission of epigenetic effects. Also, Cas13, an RNA-editing Cas protein, has the exciting potential to increase the flexibility of RNA-centered in vivo experiments.  

Could you name a moment of failure (and which lesson did you learn from it)?

I have failed many experiments, but most of the time, I enjoyed the process of making things work. Perhaps the most memorable “failure” was that my first thesis project did not work out. It was a genetic screen that resulted in no positive candidates for the pathway I was interested in, and I was already a third-year student by then. In the beginning, it was hard to imagine how I could bounce back and get my Ph.D., but I learned to work more efficiently, think more critically, communicate better, and make decisions more independently. I learned to drive my own project and ask for help. It was a lesson that still benefits me today and gives me confidence in difficult situations.

What was the greatest success in your career?

I got a lot of satisfaction from my Ph.D. and postdoc work that led to the line of research I am in now and have very fortunately made it through some career milestones so far. However, I would choose the defining moment of moving on from my first failed thesis project and building up another one that resulted in an exciting publication as my greatest success. Through it, I discovered the strengths I did not know I had and the areas in which I could grow.

Which advice would you give to young researchers?

Stay focused and driven. Do not be scared of failures and setbacks. Someone commented to me once that if I do not try anything new, I will never fail. It is very true. But it would be a pity to miss good things in life that only come with trying new things, like meeting interesting people, learning new skills, and gaining confidence. Also, failures are not so paralyzing anymore once you know you will bounce back no matter what. It is this confidence that can carry you through your career and life and open doors to possibilities.

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