Chuan Li is a CEHG Postdoctoral fellow in Dmitri Petrov’s Lab. She received her Ph.D. in Ecology and Evolutionary Biology with a dual degree in Statistics from the University of Michigan in 2017. Her research includes epistasis and speciation. In the Petrov lab, she studies the interaction between protein interfaces and antagonistic pleiotropy.
Can you tell us a bit about yourself, personally and professionally?
Born in a small village where my family runs a farm, I have been obsessed with observing the fabulous natural world, which attracts me to the field of biology. I love growing plants. I am also interested in linguistics. I speak multiple languages and enjoy communicating with people from different cultural backgrounds.
I received my Ph.D. in Ecology and Evolutionary Biology with a dual degree in Statistics at the University of Michigan in 2017. During my Ph.D., I worked in quantifying intergenic and intragenic epistasis at a large scale using both experimental and computational approaches with yeast as the model system. I have multiple publications on intergenic and intragenic epistasis, including a Science paper on the empirical determination of the fitness landscape and epistasis of a tRNA gene.
How did you first become interested in genetics and science? Did you always want to be a scientist?
I have loved to explore the wild and read books about biology since I was a child. Very naturally, I chose biology as my undergraduate major. Initially, I was interested in ecology and ecosystems. However, in my junior year, I read a book named Recombinant DNA: Genes and Genomes by Dr. Watson and another one named Evolution by Dr. Futuyma. I became fascinated by evolution and genetics. After having an internship in the Beijing Genomics Institute, I decided to pursue a career to study evolution from a genetics perspective.
After completing my undergraduate study, I started my Ph.D. at the University of Michigan and spent years studying yeast genetics and genomics, focusing on speciation, fitness landscape and epistasis. During my Ph.D., I have been following up on publications by Dr. Petrov’s group. I am particularly interested in their work on quantifying fast adaptation, and high-resolution lineage tracking by Bar-seq to reveal evolutionary dynamics. I met Dr. Petrov in person at a genetics conference (TAGC), where he was the coordinator for a section where I gave a presentation. Later after my PhD, I decided to come to his lab for postdoctoral research.
Can you tell us about your current research and what you want to achieve with it?
My general research interest lies in studying epistasis, which means interaction within and between molecules. The term has been widely used to describe a broad range of complex interactions among genetic loci, including the functional relationship between genes, the genetic ordering of regulatory pathways, the quantitative differences of allele-specific effects, etc.
Epistasis is a prevailing phenomenon, and the phenotypic effect of a mutation can depend on its genomic background and the potential interaction with other genes or sites. Quantifying such interaction has important theoretical and real-life applications, including understanding evolutionary trajectories, quantitative traits and complex diseases.
My current research in Dr. Petrov’s lab focuses on studying the mechanisms of cancer progression and metastasis. Cancer progression can be viewed as a fast evolutionary process, with lots of mutation happening in a short period, where epistasis would play an important role. The research is in collaboration with Dr. Monte Winslow’s Lab.
Using a technique called ultra-deep barcode sequencing (Tuba-seq), we can uncover enormous tumor growth variability and unveil the underlying genetic mechanisms. This technique uses lentiviral vectors to modulate expression of candidate genes and uses barcode sequencing to precisely measure the size of millions of DNA-barcoded tumors. Such a technique allows for quantifying the relative contribution of each tumor suppressor and their combinations, as well as responses to different treatments and treatment combinations, which can be viewed as genotype-by-genotype and genotype-by-environment interaction. Gaining such insight will greatly benefit clinical treatment for patients with various genetic backgrounds, helping to choose the correct therapy and avoid using unfruitful therapies, ultimately achieving personalized medicine.
What are your future plans? Where do you see yourself professionally in the next 5 or 10 years?
Over the course of my postdoctoral research, my goal is to understand the various underlying mechanisms of epistasis, which would greatly benefit the understanding of many complex traits, and contribute significantly to the area of synthetic biology. Through conducting research, I plan to enhance my capabilities in statistical modeling and experimental design, and hone my skills in both computational and experimental research. Enjoying the collaborative environment in Dr. Petrov’s lab and having access to substantial resources of the Stanford community, I hope my interdisciplinary background in statistics, programming and biology will substantially contribute to the completion of interesting projects.
In the next 5 to 10 years, I wish to establish my lab and keep working on fascinating cutting-edge topics with outstanding collaborators. Meanwhile, I am also looking forward to spreading relevant knowledge to the community.
Were there people in particular to whom you would attribute your professional success?
Yes, I think several people have greatly contributed to my professional success. My family has been very supportive of every decision I make. My undergraduate advisor and my Ph.D. advisor have been of enormous influence, both being a role model in conducting scientific research and training me scientifically. Moreover, my best friend from high school has been very helpful, because she kept telling me that studying biology would fit me very well, which I think had an impact on me.
Throughout my Ph.D. study, I worked on projects independently, with advice mostly from my mentor. It has been very helpful for independent research training, where I get to do every detail including asking the scientific question, conducting experimental work, analyzing the collected data and drafting a manuscript. But collaboration is very important, too.
After starting my postdoc at Stanford, I love the atmosphere of collaboration. I just started my first project here, and have benefited a lot from the discussion with multiple professors when designing my project. By taking advantage of the expertise of multiple groups, it becomes much faster to complete a project in a better way.
Can you speak a bit to the role you see CEHG playing on Stanford campus?
CEHG has been the interdisciplinary hub of Stanford genomic research from multiple perspectives, with interdisciplinary research and collaboration being the core value. Having such hubs are vital nowadays as biology research has become more interdisciplinary. My work in collaboration with Dr. Winslow’s lab embodies such values, where people from different backgrounds work together to understand cancer evolution better, and such effort couldn’t be easily completed by any individual.
What advice would you offer to other grad students or postdocs who are considering pursuing a similar (educational and career) path as you?
It would be of great importance for students to gain some knowledge or experiences in both wet and dry lab, which expands our horizons and helps us to communicate with other scientists. Also, learning some basic statistics would be of great help, and there are many wonderful on-campus and online resources for doing that. Completing a formal dual degree is another option, too.
Tell us what you do when you aren’t working on research and why. Do you have hobbies or special talents?
I love translation and doing sports. I have been doing technical translation in English, Chinese and Japanese and also serving as a volunteer translator for the community center for years. My favorite sports include tennis, table tennis and Taekwondo.