GRANTEE: Rushika Perera, PhD
University of California, San Francisco
Research Project: Targeting Nutrient Scavenging Pathways That Fuel Pancreatic Cancer Growth
Award: 2016 Skip Viragh – Pancreatic Cancer Action Network – AACR Pathway to Leadership Grant
Award Period: July 1, 2016 – June 30, 2018
Dr. Perera earned her PhD from the University of Melbourne and the Ludwig Institute for Cancer Research in Australia, studying pathways controlling glioblastoma tumor growth. Dr. Perera then began postdoctoral studies at Yale University, where she observed live cells using advanced microscopy to determine how organelles, or structures within cells that serve specific functions, move inside the cell. Dr. Perera later completed postdoctoral training at Massachusetts General Hospital Cancer Center/Harvard Medical School in the laboratory of Nabeel Bardeesy, PhD, recipient of the 2008 Randy Pausch, PhD – Pilot Grant from our organization. In Dr. Bardeesy’s laboratory, Dr. Perera focused on pancreatic cancer cell organelles. She uncovered mechanisms for regulation of a process called autophagy by which cells recycle internal components to gain nutrition. She also studied how autophagy is linked to other organelles in pancreatic cancer cells. Dr. Perera joined the faculty of University of California, San Francisco, in 2015 as an assistant professor in the departments of anatomy and pathology. Her laboratory is focused on understanding the mechanisms that drive metabolic reprogramming at the organelle level.
Pancreatic cancer cells are notoriously resilient as they’re able to survive and thrive even under harsh environmental conditions. When there is a lack of available nutrients, pancreatic cancer cells use unconventional methods to ensure proper nutrition. These include autophagy, which entails the consumption and recycling of internal components from the cell and macropinocytosis, which involves taking in fluid from outside the cell and scavenging nutrients from the fluid. Both of these processes employ the lysosome – an acidic organelle that harbors a specific set of enzymes that break down proteins and other large molecules into basic cellular building blocks. It was previously thought that the lysosome is a cellular dead end devoid of any regulation or fine-tuning. Instead, Dr. Perera theorizes that the lysosomal compartment within pancreatic cancer cells plays a critical, active role in cellular survival and disease progression.
Specifically, Dr. Perera and her team hypothesize that lysosome-derived nutrients are important for maintaining cellular metabolism. She will monitor how changes in lysosomal activity in pancreatic cancer cells under conditions of nutrient starvation or after treatment with anti-cancer agents enables adaptation to these stress conditions. Through a comprehensive analysis of lysosomal function in pancreatic cancer, Dr. Perera’s goal is to identify key targets for the development of novel lysosome-based inhibitors, which could prevent pancreatic cancer cells from surviving.