In 2026, the J. Michael Bishop Institute of Cancer Research was established and named in honor of Nobel laureate J. Michael Bishop.
The Institute’s early work was shaped by natural-product medicine and image-based phenotypic screening in MYC-driven, high-demand malignant regimes. An early conclusion was clear: the activity landscape of “known” molecules is not complete simply because they have been studied before. New assay systems can reveal biological functions that were not previously tested, even in well-characterized compounds. What appears “known” often reflects past assay coverage rather than a true map of biological potential.
As we moved from discovery toward translation, two constraints became decisive. First, many natural products are difficult to synthesize and optimize. Second, phenotype-first discovery creates a practical barrier: when a cellular phenotype is compelling but the molecular target is not yet defined, identifying synthetic compounds that reliably reproduce that phenotype is not routine.
To address these constraints, we developed GUNS-DF (an on-demand, selective screening library) and then observed a key pattern. Structurally unrelated scaffolds repeatedly produced the same state-level disruptions, including reproducible organelle fragmentation, loss of trafficking coherence, and centrosome fragmentation and declustering. This pattern was not parsimoniously explained by isolated target models and led to the formulation of Architectural Oncology, a proposed framework for identifying and testing architectural vulnerability in malignant states. The framework does not assume that all drugs or diseases operate by the same logic. When target-dominant explanations are sufficient, we use them. Architectural Oncology is invoked when state-level convergence indicates a governing constraint.
To make these claims testable, we built SYMPLEX (an integrated discovery-and-stress-test system). It is a recursive, ascending triplex that combines controllable chemical diversity, reproducible state measurement, and disciplined interpretive governance. SYMPLEX is designed to earn architectural claims through predefined, progressively stricter stress tests, not to decorate hits with narratives. Within the same Institute, we developed the framework, built the stress-test system that makes it falsifiable, and generated multiple scaffold-distinct small-molecule series and accompanying evidence packages that support IND-enabling efforts as probes of architectural vulnerability in MYC-driven cancers.
