GRANTEE: Wantong Yao, MD, PhD
MD Anderson Cancer Center
Research Project: Syndecan-1 is a Novel Regulator for Nutrient Salvage Pathway
Award: 2016 Carina Rogerson – Pancreatic Cancer Action Network – AACR Pathway to Leadership Grant
Award Period: July 1, 2016 – June 30, 2021
Dr. Yao enrolled at Taishan Medical College in China in 2001. Her five years studying medicine cultivated her strong interest in cancer research and inspired Dr. Yao to enter the PhD program at Fudan University in 2006. Her PhD training focused on the regulation and function of pancreatic cancer cells. After receiving her doctorate, Dr. Yao was recruited to the department of pancreas surgery at Shanghai Cancer Hospital, where she received further clinical training. Her daily work with patients who were bravely fighting pancreatic cancer underscored the urgency she felt for improved diagnosis and treatment options for this deadly disease. Dr. Yao is currently a postdoctoral fellow at The University of Texas MD Anderson Cancer Center, in the laboratory of Giulio Draetta, MD, PhD, principal investigator of the 2014 Skip Viragh – Research Acceleration Network Grant. Dr. Yao is co-mentored by Anirban Maitra, MBBS, recipient of multiple Pancreatic Cancer Action Network research grants and member of our Scientific and Medical Advisory Board.
Ninety-five percent of pancreatic cancer cases involve mutation of a gene called KRAS. Among the known functions of the resulting mutated KRAS protein is activation of a process called macropinocytosis, which allows the cancer cells to engulf nutrient-containing fluid surrounding the cells. The nutrients from the fluid are internalized into the cancer cells and used as building blocks to sustain the cancer cells’ survival and growth – allowing the cells to continue growing and dividing, even in otherwise unfavorable conditions. However, the mechanism by which KRAS activates macropinocytosis has not been elucidated.
In order to understand this mechanism, Dr. Yao studies mice that are genetically programmed to develop pancreatic cancer due to KRAS mutations. Specifically, she focuses on proteins on the surface (outside) of pancreatic cancer cells that may play a role in macropinocytosis. So far, she has identified syndecan-1, which is a proteoglycan, or a protein that is also covered with sugar, present on the pancreatic cancer cells’ surface and activated by KRAS to induce macropinocytosis.
For her project, Dr. Yao will seek to further understand how mutant KRAS influences sydecan-1’s localization to the cell surface and to determine how sydecan-1 affects macropinocytosis and nutrient breakdown, or metabolism, within the cancer cells. Because macropinocytosis is a means for pancreatic cancer cells to gain necessary nutrients, it seems plausible that blocking the cells’ food supply by inhibiting macropinocytosis may result in cell death. Therefore, the overall goal of this proposal is to increase knowledge and gain new insights about opportunities to block essential pancreatic cancer cell processes that may be translatable into novel therapies.