hahn lab

Gabe Kreider-Letterman

Gabe Keider-Letterman

Key to cancer cell metastasis is the ability of cancer cells to invade through their extracellular environments. The changes that occur during this process involve coordination between multiple signaling pathways that are linked to cell adhesion and matrix remodeling. The relationship between the intracellular signaling and the extracellular environment is bidirectional - intracellular signals influence how cells respond to their environment, and differences in the extracellular environment modulate intracellular signaling that determines cell behavior.

My research focuses on understanding how cancer cells sense their extracellular environment through mechanosensitive proteins, and how mechanical forces are translated into intracellular signals. To achieve this, I am pursuing the following directions:

  1. I am using the recently developed Binder/Tag approach to generate biosensors for the key mechanosensitive protein Talin, which integrates force sensing with many signaling pathways. This tool allows for precise visualization of Talin conformational changes, induced by acto-myosin forces, and the resulting changes in Talin scaffolding function. Understanding when and where tension induces scaffolding changes in Talin will reveal how Talin coordinates responses to heterogeneous forces and ECM interactions.

  2. Using our new capacity for biosensor multiplexing, I am exploring how cellular signals from the Rho family of GTPases are regulated within and around cellular adhesions. I am particularly focusing on invadopodia, degradative adhesion structures that facilitate cancer cell invasion by remodeling the ECM. Although it is known that Rho GTPase activity is regulated by invadopodia, the mechanism and role of GTPase coordination at these structures is not yet well understood. Gaining insights into Rho GTPase signaling at invadopodia will not only deepen our understanding of invadopodia-based invasion, but also have broader implications for the localized regulation of Rho GTPases by specific structures.


~Updated 02/06/2023

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