Zhi “Zack” Zheng, who is scheduled to receive his PhD from the Gerstner Sloan Kettering Graduate School of Biomedical Sciences (GSK) later this year, has received the 2025 Chairman’s Prize. The prize was established by Louis V. Gerstner Jr., the GSK Board of Trustees Chair Emeritus, for whom the school is named. It is presented annually and includes a $2,000 award.
This year’s prize was awarded to Zheng for his research on the function of a protein called SPO11, which creates double-strand breaks in DNA. When they occur, double-strand breaks can lead to genomic instability and cell death. They also are critical for the process known as meiosis, which leads to the formation of egg and sperm cells.
Zheng conducted his thesis work in the lab of molecular biologist Scott Keeney, PhD. Dr. Keeney’s lab uses yeast and mouse models to study the role of SPO11 in meiosis. Specifically, the research is focused on meiotic recombination, the process by which homologous (paired) chromosomes exchange genetic materials.
Studying Double-Strand Breaks With Purified Proteins
To conduct his experiments, Zheng purified protein complexes of mouse SPO11 with its partner protein TOP6BL after expressing them in cultured human cells. Using these materials, he was able to show how SPO11 makes double-strand breaks in DNA.
“Our study showed for the first time how SPO11 works at the molecular level,” Zheng says. “This includes how it forms complexes with other proteins, recognizes and cuts specific spots in the DNA, and avoids cutting in the wrong places.”
“Reconstituting double-strand breaks with purified proteins has been a holy grail in the meiosis field in general and has been one of the major goals of my lab since I started at MSK in 1997,” Dr. Keeney says. “Zack deserves 100% of the credit for getting this up and running. It was entirely at his own initiative.”
A New System for Studying SPO11 Activity
In February 2025, Zheng was first author of a paper in Nature that revealed important and surprising insights into many aspects of how SPO11 achieves and regulates double-strand break formation. The research showed, for example, that two SPO11 molecules must come together to create these breaks, but the resulting dimer is inherently weak, which restrains SPO11’s activity and makes it dependent on accessory proteins. It also showed that SPO11 has a sequence bias and is capable of resealing “nicks,” or cuts in a single strand of DNA.
The new system for studying SPO11 activity in the test tube opens the door to answering fundamental questions about the mechanism and control of recombination and will provide new insight into human reproductive health and disease.
A native of China, Zheng earned his undergraduate degree in biology from the Southern University of Science and Technology in Shenzhen. He then worked as a research assistant and technician at Tsinghua University for two years before enrolling at GSK.
“This valuable hands-on experience inspired me to study the molecular basis underlying biological processes using biochemical and biophysical tools,” he says. “GSK offered everything I was looking for in a graduate program — a flexible and comprehensive curriculum as well as the chance to work with a group of active and intelligent scientists working across different fields.”
Zheng is a postdoctoral fellow in Dr. Keeney’s lab. Later this year, he plans to transition to a scientist role in industry.