Chuan Liu
In Dr. James M. Berger’s lab, my research focuses on how cells start transcription-coupled DNA–protein crosslink repair (TC-DPCR). In cells, many proteins — such as histones and topoisomerases — can become covalently trapped on DNA by drugs or normal metabolic byproducts, forming DNA–protein crosslinks (DPCs). These lesions are dangerous because they can physically block DNA replication and RNA polymerase II (RNAPII) during transcription. Although it is known that a DPC can stall RNAPII and trigger TC-DPCR, how this repair pathway is initiated has been unclear. To address this, I used the topoisomerase II cleavage complex (TOP2cc) — a clinically relevant DPC induced by chemotherapies like doxorubicin — as a model lesion. I determined cryo-EM structures of yeast RNAPII colliding with TOP2cc, with and without known repair factors, and I measured transcription outcomes when yeast and mammalian RNAPII encounter TOP2cc under different factor conditions. My results show that the RNAPII–TOP2cc collision interface is flexible, which may allow early recruitment of downstream transcription-coupled repair factors without steric clashes with the bulky TOP2cc. However, the TOP2cc blocks further recruitment of TFIIH, which explains the differentiation between TC-DPCR and transcription-coupled nucleotide excision repair (TC-NER). This advances our understanding of the earliest steps of TC-DPCR. Mechanistic insight into how cells respond to TOP2cc provided by this work can also inform how chemotherapies kill cancer cells and how resistance or toxicity might arise.
Questions & Answers
Why did you choose Johns Hopkins for your work?
Johns Hopkins was the first research university in the U.S. I’m drawn to its profound historical and cultural heritage and its strong foundation in research. Another major reason is that James is a world-renowned biochemist and structural biologist, and I believe that training in his lab will prepare me well for a future academic career.
What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received?
Personally, receiving the Alfred Blalock Award is meaningful to me because it recognizes years of persistence. As someone new to this field, it’s an encouraging affirmation that the questions I chose to pursue truly matter. Professionally, it is a strong validation of my research direction and an important boost to my credibility. It will help me build new collaborations and pursue the next stage of this project with greater momentum. Alfred Blalock is a pioneer of neonatal cardiac surgery; I admire his courage to challenge established limits, and I aim to carry that same courage in pursuing ambitious scientific questions.
What contributed to your project’s success? (Special skills, interests, opportunities, guidance, etc.)
My Ph.D. training in China laid a solid foundation for my postdoctoral research. More importantly, James provided strong scientific and financial support and gave me the freedom to explore new ideas independently. The success of my project also wouldn’t have been possible without the help of everyone in Berger lab and my collaborator Fan Zhao in Wolberger lab.
What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles students and fellows play in research at Johns Hopkins?
Most scientific awards go to well-established, highly accomplished scientists. Far less attention is paid to early-career researchers, who often face substantial uncertainty and pressure to build an independent academic path. Young Investigators’ Day shines a spotlight on these young scholars and signals recognition from Johns Hopkins and the broader scientific community. It can significantly boost their confidence and help cultivate the next generation of scientists.
What has been your best/most memorable experience while at Johns Hopkins?
My best experience is working with so many talented scientists to expand the frontiers of science and serve the well-being of humankind.
What are your plans over the next year or so? Graduating, looking for faculty positions, etc.?
I will stay in Berger lab for the next few years to refine this project. After that, I may pursue a faculty position.
Tell me something interesting about yourself that makes you unique. Do you have any special hobbies, interests or life experiences?
Fun fact: Prior to my postdoctoral training, I spent more than a year working in industry.
Hobbies: I have so many hobbies that weekends are never long enough. I love everything outdoors, especially gardening.