Henry Yi Cheng
Mutations in isocitrate dehydrogenase (IDH1/2) are the most common metabolic alterations in human cancers and drive production of the oncometabolite D-2-hydroxyglutarate (D-2HG). As the “poster child” of cancer metabolism, D-2HG has been intensely studied across different cancers for nearly two decades; however, a central question has remained unresolved: how this highly charged metabolite exits tumor cells to shape the tumor microenvironment. In this study, we identified the volume-regulated anion channel (VRAC) as the principal conduit for D-2HG release from IDH-mutant cells and a key driver of tumor immunosuppression. Surprisingly, we discovered that VRAC-mediated D-2HG efflux also serves as a previously unrecognized D-2HG clearance mechanism that is essential for maintaining mIDH tumor cell fitness. By exporting D-2HG, VRAC prevents excessive intracellular buildup that would otherwise induce mitochondrial metabolic stress, epigenetic reprogramming and impaired proliferation. This work, along with my other Ph.D. studies, was performed in Dr. Zhaozhu Qiu’s lab in the Department of Physiology, Pharmacology, and Therapeutics (PP&T).
Questions & Answers
Why did you choose Johns Hopkins for your work?
Hopkins is a historic research university that has fostered many foundational discoveries in human history. Coincidentally, although I didn’t know it when I joined, the initial discovery of IDH mutations was made at Hopkins by Dr. Ken Kinzler. I came to Hopkins for rigorous, comprehensive scientific training and a culture that values deep mechanistic work. The strength of the research community and the collaborative environment here have made it an ideal place for my growth and development as a scientist.
What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received?
Receiving this award is a tremendous honor. It recognizes the research contributions I have made in the Qiu lab. Dr. Paul Ehrlich has long been an inspiration to me, representing the kind of research I hope to pursue and the scientist I aspire to become. I have known — and been inspired by — several previous recipients of this award, and I am honored to be counted among them. Professionally, this recognition motivates me to continue pursuing rigorous, impactful research and to never underestimate the importance of fundamental biological questions.
What contributed to your project’s success? (Special skills, interests, opportunities, guidance, etc.)
I attribute the success of this work to the collective effort of past and current members of the Qiu lab and our collaborators. I have also been fortunate to be mentored by Dr. Zhaozhu Qiu, who gave me significant research freedom while consistently offering invaluable scientific insight. I learned a great deal from his scientific vision and from the way he frames and communicates research questions. He has been an important role model for me as a thoughtful and rigorous scientist. The CMP graduate program and the PP&T department provided a kind, welcoming environment and strong support for Ph.D. students. I am also grateful to my thesis committee — Drs. Xinzhong Dong, Steven Claypool, Andrea Cox and Nathan Archer — for their guidance, thoughtful feedback and steady encouragement throughout my Ph.D. training. Overall, I feel very fortunate to learn from these leaders in science and medicine as we tackle small, but hopefully meaningful, questions.
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?
Research can be challenging and, at times, isolating, and we often have to troubleshoot and push through obstacles day to day at the bench. Events like Young Investigators’ Day are invaluable because they give us a chance to step back, see the outstanding work of our peers, and connect through conversation. Sharing our experiences and excitement for discovery helps sustain motivation and reminds us that we are part of a larger scientific community.
What has been your best/most memorable experience while at Johns Hopkins?
I’ve had many great moments at Hopkins, both inside and outside the lab, but one of my favorites has been the annual Christmas parties at Zhaozhu’s home. They were a chance to relax, connect with colleagues and celebrate the year’s hard work and accomplishments. Talking, playing games and spending time together helped us recharge and come back energized for the year ahead.
What are your plans over the next year or so? Graduating, looking for faculty positions, etc.?
I plan to graduate in late Fall this year, and have begun my postdoc job search. I hope to join a lab where I can investigate how metabolites function as signaling molecules and how they shape cellular programs and immune responses.
Tell me something interesting about yourself that makes you unique. Do you have any special hobbies, interests or life experiences?
I’m an avid classical music fan, and through student ticket programs I attended National Symphony Orchestra, Baltimore Symphony Orchestra and Philadelphia Orchestra concerts 20–30 times in a single season. Being based in Baltimore makes it easy to hear world-class ensembles regularly. In 2024, when the Bavarian Radio Symphony Orchestra toured the U.S. East Coast, I attended their concerts in both D.C. and Philadelphia within a three-day span.