GRANTEE: Bjoern Papke, PhD
University of North Carolina at Chapel Hill
Research Project: Visualization of KRas Perturbations in 3-dimensional Pancreatic Organoids
Award: 2016 Pancreatic Cancer Action Network – NCI Frederick National Laboratory for Cancer Research KRAS Travel Scholarship
Award Period: March 1, 2016 – February 28, 2017
Biographical and Research Highlights
Dr. Papke is a postdoctoral researcher in the University of North Carolina at Chapel Hill laboratory of Channing Der, PhD, who is a two-time Pancreatic Cancer Action Network research grant recipient and a member of our Scientific and Medical Advisory Board. Dr. Papke earned his MSc in cell biology from the University of Witten/Herdecke, Germany. His PhD studies were conducted at the Max Planck Institute of Molecular Physiology in Dortmund, Germany. There, Dr. Papke’s work focused on the discovery of small molecules that could block the protein KRAS from being located at the cellular plasma membrane, thereby blocking its activity. KRAS is in a mutated form in 95 percent of pancreatic cancer cases. Dr. Papke’s doctoral work led to several high impact publications and uncovered a potential method to block mutant KRAS activity as a treatment strategy for pancreatic cancer.
In his current position in Dr. Der’s laboratory, Dr. Papke will study pancreatic cancer cells using a novel three-dimensional experimental strategy. Pancreatic “organoids” are tumor-like structures that can be established in the laboratory from tissue taken directly from patients’ pancreatic tumors, allowing the analysis of the pancreatic cancer cells in conjunction with the stroma, the complex mixture of other types of cells that surround and infiltrate pancreatic tumors. By contrast, the more commonly used two-dimensional cell culture methods only allow the study of the cancer cells themselves, grown in two dimensions on a dish, a model less relevant to real-life conditions.
Dr. Papke proposes to visualize the pancreatic organoids using advanced light microscopy techniques. This will allow him to observe how the cells behave differently (for example, protein signaling that is activated) when mutant KRAS is present or its activity is blocked. As part of his research project, Dr. Papke will travel to Frederick National Laboratory (FNL), the hub for the National Cancer Institute RAS Initiative, to develop an imaging technique that will enable him to observe mutant KRAS interacting directly with other proteins. Dr. Papke will further utilize the imaging techniques to study the consequence of experimental methods of altering mutant KRAS signaling, or series of protein changes elicited by mutant KRAS activity. Imaging will also allow observation of the timing and physical location of these events within the cells. The cellular imaging-related reagents, instrumentation and expertise found at FNL will enable Dr. Papke to develop these imaging techniques to improve our understanding of KRAS signaling and how it might be affected by drug interventions.