Advanced Therapy

Pancreatic tumors are remarkably diverse in character and behavior, and a patient's response to therapy may differ substantially across subpopulations of cancer cells. Developing effective, precise treatments will demand that we understand and control for this diversity. Through Atlas and a number of other research projects, we are seeking to understand the complex biology of the pancreas at a cellular and molecular level. We also collaborate with other cancer programs, including OHSU's SMMART Trials program, Serial Measurements of Molecular and Architectural Responses to Therapy, which uses our research analyses to follow patients as they progress through each line of treatment.

Ongoing research projects

There is a critical need to generate robust patient-derived laboratory models that can be used to increase our understanding of the biology of pancreatic cancer and to identify better therapeutic strategies.  Patient-derived models of cancer provide critical tools to understand aspects of cancer biology and therapeutic response specific to a patient's tumor that cannot be studied in humans. In order to use patient-derived models to improve patient clinical care, it is essential that the scientific community understands the strengths and limitations of each type of model. Our primary goals are to identify the molecular and phenotypic features of primary tumors that can be recapitulated by various patient-derived models, and to determine how well relative therapeutic response within each model type aligns with relative response among patients.  The Sears, Coussens, Demir and Gray labs are collaborating on this project.

  • 3D bioprinting of tumor and microenvironment
  • Lineage plasticity in therapeutic resistance
  • Neuroendocrine transdifferentiation of PDAC cells in tumor progression and chemoresistance
  • Phosphorylation-directed prolylisomerase Pin1 in TME remodeling
  • Post-translational activation of c-Myc in pancreatic cancer
  • Role of Myc in progression and heterogeneity
  • PP2A activation in PDAC
  • Propagation of conditionally reprogrammed patient tumor cells
  • Effects of BTK inhibitor on B cell, T cell, and myeloid biomarkers in clinical trials
  • Evaluating immune-modulating therapies in combination with chemotherapy
  • Identifying circulating biomarkers of immune therapies
  • Correlative light and electron microscopy analysis of drug delivery (Gray)
  • Electron microscopy of PDAC (Gray)
  • Microenvironment microarray (Gray)
  • Network based functional genomics (Gray)
  • Developing IHC/IF CLIA-validated methods for pathway biomarker analysis (Gray, Coussens)
  • Quantification of fluorescently labeled drug distribution for PDAC using CLEM (Gibbs)
  • Identifying resistance mechanisms in pancreatic cancer evolution (Heiser)
  • Intratumoral heterogeneity of pancreatic cancer (Johnson)
  • Longitudinal studies of pancreatic cancer (Muschler)
  • 3D molecular interrogation of intact human pancreatic cancers (Muschler)
  • Phosphoproteome in PDAC
  • Predictive Markers for Therapeutic Response
  • High-throughput screening of organoids (Dorrell)
  • Noninvasive MRI assessment of tumor microvasculature and associated macrophages using magnetic nanoparticles (Guimaraes)
  • Identification of novel chromatin-interacting therapeutic targets in PDAC (Sherman)
  • Transarterial nanoparticle imaging and combinatorial phototherapy for pancreatic cancer (Farsad)
  • TIME* matters in pancreatic cancer (*tumor immune microenvironment) (Chang)