MUSC Hollings Cancer Center researcher Wenjian Gan, Ph.D., recently received two prestigious grants that will fuel innovative breast cancer research to identify novel treatment targets.
The American Cancer Society Research Scholar Grant provides Gan with $792,000 over four years, and the National Institute of General Medical Sciences Maximizing Investigators’ Research Award (MIRA) provides $250,000 in direct costs per year for five years. These grants secure funding stability and protected time for Gan’s growing lab and promising breast cancer research projects.
“I am excited and thankful to receive both grants. It is very encouraging to know that the scientific community believes my research ideas are important. This stable funding will allow me to recruit more people, train future scientists and fill in some of the missing scientific puzzle pieces so we can find more effective cancer treatments,” said Gan, who is an assistant professor in the Department of Biochemistry and Molecular Biology in MUSC’s College of Medicine.
Gan started his lab at MUSC in October 2018 after receiving his Ph.D. at Peking University in Beijing and completing his postdoctoral training at Beth Israel Deaconess Medical Center at Harvard Medical School. “To me, the most exciting thing about being an independent investigator is that I can develop these ideas, propose experiments and get the exciting results that show that my hypothesis was correct or guide us in the proper direction. I am very thankful that I now have excellent trainees in my lab who can help develop these exciting grant projects,” said Gan.
Gan’s research focuses on understanding how post-translational modifications regulate cell signaling and genomic instability, which affects breast cancer progression. Post-translational modification is a biological process that uses enzymes, specialized proteins that speed up reactions, to modify certain amino acids after proteins have been made. While post-translational modifications are necessary to increase protein diversity in cells, diseases such as cancer may develop if errors occur during this process.
“Targeting the enzymes that regulate these post-translational modifications is currently a key approach to treat cancers. My research revolves around a family of enzymes called protein arginine methyltransferases, or PRMTs, which modify the arginine (an amino acid) residue on proteins. We are working to understand how PRMTs are regulated and exert their functions so we can develop inhibitors or strategies to block this process when it goes wrong,” said Gan.
Breast cancer is the most commonly diagnosed cancer worldwide and the second leading cause of cancer death in women in the U.S. Despite treatment advances, the more aggressive breast cancers still have few treatment options and poor prognosis. Fortunately, life-changing cancer therapies are being born out of intensive molecular research, leading to the development of more personalized and effective treatment options.
“One of the PRMTs — PRMT5 — is overexpressed in more than half of primary breast tumors and 70% of metastatic breast tumors. The highest levels are found in triple-negative breast cancer, which is also the hardest to treat. The higher levels of PRMT5 correlate with reduced survival in triple-negative breast cancer patients,” said Gan.
Although PRMT5 inhibitors are currently in clinical trials, the upstream molecules that regulate PRMT5 function and the efficacy of PRMT5 inhibitors remain largely unknown. As part of his American Cancer Society Research Scholar Grant project, Gan and his team will focus on understanding the molecules that regulate PRMT5, using breast cancer cell lines and mouse models. These findings should shed light on how to improve the anti-tumor efficacy of PRMT5 inhibitors.
The MIRA grants support ambitious scientific projects that propose a creative approach to finding answers to critical scientific questions. “Although PRMTs were actually identified 30 years ago, PRMT inhibitors only recently moved to clinical trials. There is so much that we do not know. The better we can understand a molecule, the better we can target it to achieve effective therapeutic response,” said Gan. This award will support three separate projects, all of which dissect different aspects of the regulation and functions of PRMTs. The long-term goal is to develop novel strategies and inhibitors to target the PRMT pathway for cancer therapy.
Gan explained how Hollings’ shared resources have served as a great asset to his projects. “The shared resources have really helped facilitate my research, since it takes a team to understand all of the data. Our collaborations with other investigators and staff across the University helped lay a solid foundation for my future research programs.”