The Pancreatic Cancer Action Network-AACR Pathway to Leadership Grant represents a joint effort to ensure the future leadership of pancreatic cancer research by supporting outstanding early career investigators beginning in their postdoctoral research positions and continuing through their successful transition to independence.
Dr. Bryant is currently a postdoctoral researcher in the laboratory of Channing Der, PhD. Dr. Der is a two-time Pancreatic Cancer Action Network grant recipient and a member of the organization’s Scientific and Medical Advisory Board. Dr. Bryant received her BS degree from Bucknell University and earned her PhD at Cornell University. She joined Dr. Der’s lab in 2013. Dr. Bryant will be co-mentored by Pancreatic Cancer Action Network grantee Alec Kimmelman, MD, PhD, and grantee/adviser Anirban Maitra, MBBS.
Dr. Bryant is fully committed to a career in pancreatic cancer research. She experienced firsthand the devastation of this disease by losing her father during her final year of graduate school. This experience instilled in her the dire need for better pancreatic cancer therapeutics. Dr. Bryant has chosen to study pancreatic cancer metabolism because she believes that this new and expanding field has the potential to provide new targets that will translate to improved therapies.
More than 95 percent of pancreatic cancer cases are thought to involve mutation of a protein called KRAS. Activated KRAS contributes to the initiation, maintenance and progression of the disease. A relatively recent finding is that mutated KRAS influences pancreatic cancer cells’ metabolism, or ability to break down nutrients to contribute to cellular survival and growth, but how this happens is poorly understood. Dr. Bryant therefore proposes to define the protein signaling mechanisms that drive KRAS-dependent metabolic alterations.
Specifically, Dr. Bryant’s project involves three aims. First, she will focus on a process called autophagy, which entails a cell degrading and “eating” unnecessary proteins and other pieces of the cell in order to promote survival. Dr. Bryant’s studies will involve understanding the link between KRAS and autophagy, determining the effects of blocking a component of KRAS protein signaling combined with autophagy inhibition and understanding how autophagy relates to other metabolic processes and KRAS-dependent signaling pathways. Next, she will investigate the relationship between mutant KRAS and another cellular process called macropinocytosis, which allows the cell to bring in fluid and particles from immediately outside the cell as another source of nutrition. Finally, Dr. Bryant will define KRAS-dependent changes in gene expression that influence cellular metabolism of an amino acid, or building block of proteins, called glutamine. Overall, she will perform basic mechanism-focused studies to better understand how mutant KRAS drives pancreatic cancer growth. By identifying the signaling mechanisms that drive KRAS-dependent upregulation of autophagy, macropinocytosis and glutamine metabolism, Dr. Bryant aims to determine if inhibitors of these processes, alone or in combination, will serve as effective treatments for pancreatic cancer.
GRANTEE: KIRSTEN BRYANT, PHD
University of North Carolina at Chapel Hill
Research Project: Exploiting pancreatic cancer cell metabolism for therapeutic gain
Award: 2015 Pancreatic Cancer Action Network – AACR Pathway to Leadership Grant
Award Period: October 1, 2015 – September 30, 2020 Amount: $600,000