What’s under the hood of a metastatic cell?

A Toyota Camry and a Lamborghini Aventador have engines that operate on the same basic principle, yet deliver dramatically different performance on the track. Their components, configuration, and tuning determine what they can do—and what they require to do it.

For a metastatic cell, success depends on performing across remarkably different conditions: escaping a tumor, surviving transit, and establishing itself in unfamiliar tissue. We investigate how the composition and organization of mitochondrial machinery make this adaptability possible. By reverse engineering what equips these cells to succeed, we aim to identify—and disrupt—the metabolic requirements of their journey. Our goal is metastasis prophylaxis: preventing cancer cells from acquiring or sustaining the capabilities they need to spread.

How does a cell read a world it cannot see?

Cells cannot see, but they can touch and taste. They probe the resistance of their surroundings and sample the nutrients available to them, reading a kind of biochemical braille. We study how these signals work together to guide metabolism and determine whether cells pull on their environment or build materials that change it. We ask how aging and metabolic stress alter this exchange, and whether responses that initially help cells cope can become self-reinforcing sources of fibrosis. By recreating the physical and chemical conditions of human tissues, we aim to understand where this conversation breaks down—and how to restore it.

Can a cancer cell build its own camouflage?

Camouflage changes what an observer can detect. Cancer cells can alter what the immune system encounters by changing the sugar-rich coat on their surface. We investigate how tissue mechanics, nutrient availability, and mitochondrial stress shape the production of this coat—and how those changes affect immune recognition and killing. We also ask whether cells carry this protection with them when they leave a tumor. By identifying the metabolic requirements for building and maintaining these surfaces, we aim to make cancer cells more vulnerable to immune clearance.

Can an immune cell reach what it needs to make an anti-tumor response?

A key can fit a lock perfectly and still be useless if it cannot reach the keyhole. Immune recognition faces a similar problem: a cancer cell may display the right molecular targets while presenting a surface that makes them difficult to engage. We study how cell shape, membrane folds, and surface coatings influence these encounters. We are developing probes with adjustable molecular reach to map which parts of a tumor cell are accessible, alongside models that reproduce the physical and nutrient conditions of human tissues. Our goal is to understand what turns molecular recognition into productive immune contact.

What holds a tissue together as it ages?

A building can remain standing while its supporting structures gradually lose the ability to share a load. We ask whether a similar process unfolds in aging breast tissue. The cells lining mammary ducts maintain an open interior while staying connected to their neighbors. We test whether changes in the sugar-rich coat facing that interior shift more of the mechanical burden onto cell–cell junctions, altering tissue organization and cell identity. By identifying how this balance changes with age, we aim to find ways to preserve the architecture that helps keep tissues healthy.

Who builds the barriers that keep immune cells out?

A security team cannot protect a building if the corridors keep it from reaching the threat. In tumors, collagen-rich networks can redirect immune cells and alter their activity. We study collagen-synthesizing tumor-associated macrophages and ask how their matrix production shapes immune access and function. We also examine which collagen–immune-cell contacts impede T-cell movement or function. By separating the builders, the materials, and the interactions that create exclusion, we aim to identify ways to restore effective immune access.

How does cancer turn treatment stress into a survival strategy?

Stopping a production line can force a factory to reroute the work that keeps it running. We ask whether cancer cells respond to treatment in a similar way, redirecting metabolism to withstand stress and sustain essential cellular structures. In pancreatic cancer, we investigate how signals from the surrounding matrix influence these adaptations, including the production of nucleotides and sugar-based materials. By tracing where nutrients go as cells respond to treatment, we aim to identify the dependencies of surviving cells and block the adaptations that allow disease to persist.
