Zhengping Zhuang, M.D., Ph.D.
Zhengping Zhuang, M.D., Ph.D., is a world-renowned expert in experimental pathology, cancer genetics and cancer therapeutics. Throughout his career, he has focused on investigating the role of inherited and somatic mutations in tumor pathophysiology, particularly in tumors of the central nervous system. This work led to the characterization of four genes linked to cancer causation, one of which is associated with a disease now named after him and his colleague. Zhuang has also contributed to biotechnological advancements, drug development and clinical translation of his work in tumor biology. After serving the NCI for 32 years, Zhuang has announced his retirement.
Zhuang received his M.D. at the Shanghai Jiao Tong University School of Medicine in Shanghai, China. He completed his Ph.D. in pharmacology at Wayne State University in Detroit, Michigan, followed by a fellowship at Massachusetts General Hospital. Zhuang then moved back to Michigan, where he completed his residency in transitional medicine at the Henry Ford Hospital, a training program associated with the University of Michigan.
Zhuang served as a research associate at the University of Michigan before moving to the NCI in 1993, where he started as a resident in anatomic pathology in the Department of Pathology. He served as a staff pathologist and special expert for the Surgical Neurology Branch for 17 years. In 2017, Zhuang joined the Neuro-Oncology Branch as a Senior Investigator and Head of the Cancer Stem Cell Biology Research Program.
Throughout his career, Zhuang has published more than 400 articles. He co-discovered the role of the menin gene in multiple endocrine neoplasia Type 1; the role of the c-MET gene and trisomy in papillary renal cell carcinoma; and the role of the HIF2A gene in a novel tumor-associated syndrome of multiple paraganglioma, somatostatinoma, and polycythemia, a disease now referred to as Pacak-Zhuang syndrome. Recently, he also co-discovered a role for the gene SF3B1 for pituitary prolactinoma. He holds eight patents and has 17 more pending.
In the Q&A that follows, Zhuang reflects on his career and provides advice for the next generation of scientists.
Throughout your career, what scientific achievement are you most proud of?
One early invention I’m pretty proud of is a technology called laser capture microscopy (LCM). When we talk about cancer tissue, it’s not just cancer cells, you also see all different varieties of vascular cells and immunoreactive cells. At the time of my residency training, people just took the whole piece of tissue to do the genetic analysis or protein study. I thought that was inaccurate, so I started thinking about how to develop a technology to separate individual cells in the tissue.
I developed a tool from a pipette that could be used to isolate tumor cells under a microscope. And then, with my Chairman, Lance A. Liotta, M.D., Ph.D., and fellow pathology resident, Michael Emmert-Buck, M.D., Ph.D., we developed an automated machine that could isolate cells without having to do everything manually. We started around 1995, and almost 30 years later, it’s still very popular.
We used this tissue microdissection technology to identify several important cancer genes. One of those was eventually named after me and my colleague, Karel Pacak, M.D., Ph.D. That disease has now been listed with the World Health Organization and is taught in medical school. How often in a lifetime do you get to find a completely new disease and have it named after you?
Another discovery I am proud of is a drug I invented, LB100. The current thinking on how to treat cancer is to suppress tumors. But I found sometimes, going the opposite way and stimulating tumors causes them to become more vulnerable to treatment. LB100 blocks phosphatase rather than protein kinase, causing the tumor cells to become more active and replicate, and it attracts more attention from the immune system. Then, you can inject a tumor vaccine and the body’s immune cells can start to attack the tumor. There are clinical trials at MD Anderson, City of Hope and the Netherlands Cancer Institute in Europe testing LB100.
Tell me about your career journey. What brought you to the NIH?
When I was very young, I saw many of my relatives and neighbors die from cancer. Everybody was afraid of the disease, but there was very little knowledge about it. I decided that, one day, I wanted to find out what caused cancer, and that is what led me to go to medical school in China. But I realized medical school was not enough—we didn’t know much about the detailed molecular mechanisms behind cancer. So, I came to the US and did my molecular pharmacology Ph.D., and then I came to the NIH to pursue residency training in pathology.
I am always curious about the underlying mechanisms of disease. And I believe once you understand a disease, you can create a lot of technology, novel therapeutics and drug development. And NIH is the perfect environment for that—it allows you to do a lot of high risk, innovative work.
I have made a lot of unique discoveries throughout my career. Many people are surprised and say that after all these years, you must reach a peak. But I have so many observations and questions that I never feel like I am running out of ideas.
How did the intramural environment of CCR and NIH help your research?
From day one, when I developed the crazy idea of tissue microdissection with my fellow resident, Michael Emmert-Buck, and pathology attending, Irina Lubensky, we talked to Lance Liotta and he found a bioengineer with NIH, Robert Bonner, Ph.D. The technology office also connected us to a company in California that could develop the laser technology. The connections NIH provides are very helpful for technology development. Another unique aspect is our multidisciplinary population. If you want a mitochondria or proteomics specialist, you can find one, or even someone to help with drug development. It’s very, very hard to find such a condensed population of varied experts outside of the NIH.
What advice do you have for people who are just starting out in their careers?
I have had almost 60 postdocs and other trainees, and many of them went on to become neurosurgeons, physician-scientists and even PIs. I encouraged them to find a disease or question they were curious about and to conduct research. But at some point, many projects failed or they did not see results in a study. The most important thing is that you have to start somewhere. If you don’t start, you will never learn anything or find new opportunities. So, this is what I always advise—no matter how tough it is, just do it. When you do it, you will discover something, even if it isn’t what you thought it would be.
What are you looking forward to most in your retirement?
I’m looking forward to enjoying some of my hobbies. I will still work with some labs so that I can continue to do some research and help train young scientists. I’m not stopping my work completely, but just changing my way of life. I will have the freedom to do some traveling and meet friends and relatives, but on the other hand, I want to continue interacting with the scientific community and my collaborators. I also like food, and I may try to learn how to cook.
I’m also working with a Japanese company to develop a device with high-throughput automated histologic consecutive sectioning, staining and image capturing of a tumor tissue on a film or tape, and then allow AI to reconstruct the images and create a 3D model; we just had a patent issued. I want this machine to go to every hospital, so that pathologists will not have to look at the microscope anymore—they will see 3D images on their computer like CT scans for a radiologist. I’m very excited about this.
Dr. Zhengping Zhuang will retire from CCR on June 28, 2025, but will remain as an NIH Scientist Emeritus.