Tumor Ecosystem Biology

Our goal is to identify opportunities to interrupt tumor progression, restore anti-tumor immunity, and improve therapeutic responses.

Our research

Pancreatic cancer remains a major therapeutic challenge, with tumors often able to adapt to treatment and evade immune attack. Interactions between cancer cells, immune cells, fibroblasts, and the extracellular matrix shape the tumor ecosystem, influencing tumor growth, immune activity, and therapeutic response. Understanding these interactions is central to finding new ways to intervene.

Our research asks how this ecosystem becomes established and how its internal organization enables immune evasion and promotes adaptation to therapy. We address these questions from the earliest stages of pancreatic cancer through progression and treatment resistance.  Central to our work is in vivo spatial functional genomics, which combines genetic perturbations with spatial profiling to test how specific genes shape cancer cell behavior and the surrounding tissue. Preclinical models and bioinformatics help us investigate these mechanisms and integrate findings across molecular, cellular, and tissue scales.

Tumor initiation and ecosystem evolution

The tissue conditions in which a tumor arises may influence its subsequent development. We investigate how host factors, environmental exposures and inflammation shape early pancreatic cancer. Using preclinical models and lineage tracing, we follow emerging lesions and their surrounding tissues to understand how transformed cells and their neighbors establish distinct tumor ecosystems. A central question is when immune-evasive programs emerge and how they influence subsequent tumor progression.

Intratumor heterogeneity and immune niches

Individual pancreatic tumors contain diverse cancer cell states and spatially distinct tissue environments. We investigate how this heterogeneity shapes immune cell access and function, and why some local environments support treatment-resistant populations. Combining CRISPR screens with spatial profiling and imaging, we test how interactions between cancer cells, fibroblasts, immune cells, and the extracellular matrix establish and maintain these niches.

By following how these niches change during therapy, we aim to identify the cellular interactions and tissue features that allow cancer cells to persist. We also ask whether redirecting local immune activity can promote tumor cell clearance and provide a basis for more effective combination therapies.