MolecularMetastasisLab

Extracellular signals, including growth factors, cytokines, and metabolites, do not act in isolation. They cooperate with cell state-specific intracellular networks to assemble distinct transcriptional machinery, the molecular "keys" through which signals access the genome. Yet each cell state presents a unique chromatin landscape, a selective "lock", that constrains which keys work and which doors open.

The outcome of any signal is therefore not fixed. It is contingent on cellular context. The same input can elicit fundamentally different transcriptional programs depending on the chromatin environment it encounters and the signaling networks already active within the cell. Identity signals become refracted; the same extracellular cue generating entirely distinct spectra of gene expression that define and maintain distinct cell states.

Cell states are not static. As tissues progress through regeneration, fibrosis, aging, and metastasis, the chromatin landscape shifts, altering how signals are interpreted and which gene programs are executed. This dynamic reinterpretation of identical signals drives cell state transitions that determine whether a tissue heals, remodels, or transforms, and whether a disseminated cancer cell remains dormant or reactivates to seed metastatic growth.

We seek to understand this logic of signal interpretation; how cellular context encodes signal meaning, how cell states are established and maintained, and how disruptions in this decoding drive pathological state transitions across fibrosis, aging, and metastasis.

OUR RESEARCH

TRANSCRIPTIONAL CONTROL

How Signals Choose Their Targets

Cells exposed to the same signal can execute fundamentally different transcriptional programs, yet the logic governing this selectivity remains poorly understood. We investigate how signaling pathways assemble context-specific transcriptional complexes, remodel chromatin, and selectively activate or silence gene programs. Our goal is to illuminate the principles by which the same signal is translated into fundamentally different transcriptional outcomes across cellular contexts.

2. TISSUE ARCHITECTURE

Space as a Regulatory Language

Tissues are not uniform environments. They are spatially organized systems where position encodes information. We explore how tissue architecture integrates multiple signals into coherent transcriptional states. By mapping how tissue architecture context shapes chromatin landscapes and gene selection across homeostasis, injury, regeneration, and aging we aim to decode how anatomical structure itself functions as a layer of gene regulation.

3. CELL STATE TRANSITION

The Logic of Fate Switching

Cancer metastasis and therapy resistance are not random events. They reflect discrete cell state transitions governed by transcriptional and epigenetic reprogramming. We dissect the molecular logic by which pathological signals, including inflammation, fibrosis, and metabolic stress, redirect cell state trajectories to drive metastasis. Our goal is to identify the regulatory switches that determine whether a disseminated cancer cell remains dormant or reactivates, ultimately enabling precise intervention in metastatic progression.