2019 Grantee: Yuan Chen, PhD
University of California, San Diego
Research Project: Activating Anti-Tumor Immunity by Targeting a Ubl Modification
Award: 2019 Pancreatic Cancer Action Network Translational Research Grant
Award Period: July 1, 2019 – June 30, 2021
Shortly after receiving her PanCAN grant, Dr. Chen was appointed professor of surgery at University of California, San Diego. Prior to that, she was the dean of transdisciplinary research and professor in the department of molecular medicine at the Beckman Research Institute of the City of Hope. She obtained her PhD in structural biology and biochemistry from Rutgers University. She then conducted postdoctoral studies at the Scripps Research Institute before joining Beckman Research Institute of the City of Hope as faculty in 1994.
Her current research interests center on the role of ubiquitin-like modifications in major oncogenesis pathways and anti-tumor immunity, and on the development of therapies to target novel mechanisms to treat recalcitrant cancers like pancreatic cancer.
Immunotherapies, using the patient’s immune system to fight off their cancer, have greatly improved treatment of several solid tumors, extending patient survival and reducing side effects compared to traditional chemotherapy. However, patients with pancreatic cancer have not benefited from this approach, largely because the immune cells present in the tumor are not the ones that respond to immunotherapy. In fact, the cells act to suppress the immune response by blocking other anti-cancer immune cells from entering the tumor. The goal of Dr. Chen’s proposed study is to characterize a new target and mechanism that her research team expects will remove the immune privilege of pancreatic cancers so that an anti-tumor immune response could be achieved to improve patient outcomes.
The proposed study aims to enhance the role of immune cells that confer long-term memory against cancer, known as T-cells. Two types of T-cells play key roles in fighting pancreatic and other cancers: effector T-cells that kill cancer cells and regulatory T-cells that inhibit the activity of effector T-cells. Emerging research and Dr. Chen’s preliminary data indicate that blocking the signaling pathways controlled by a mechanism known as SUMOylation (small ubiquitin-like modifications) reduces regulatory T-cell numbers and function, while enhancing the ability of effector T-cells to infiltrate and kill cancer cells. The proposed studies will further investigate these effects and help Dr. Chen and colleagues understand the mechanism using mouse models and novel drugs to inhibit this pathway.
Dr. Chen has gathered a transdisciplinary team of doctors and scientists who are leaders in cell signaling and immunity, pancreatic cancer and surgical oncology. This innovative research leverages City of Hope’s outstanding research infrastructure, which focuses on rapidly translating new discoveries into more effective therapies for patients. They believe these studies have the potential to transform pancreatic cancer therapy.