Laboratory of Becky Worthylake, PhD

 

Monocyte (yellow) crawling on an endothelial monolayer

Leukocytes, flowing though the bloodstream, respond to infection by migrating across the blood vessel wall and into the infected tissue. Leukocyte recruitment is an important component of the body’s immune defense system; however, when misregulated, inappropriate inflammatory responses actually cause a large variety of pathologies. In addition, metatstatic tumor cells that break away from the primary tumor and colonize growth at distant sites often “hijack” the leukocyte cell migration and recruitment mechanisms.

 

 

The goal of my laboratory is to answer the question –

How Do Cells Know Where To Go?

Cell Systems:

Monocyte migration across endothelium in response to fractalkine (CX3CL1). Fractalkine is a chemokine associated with monocyte recruitment during the development of atherosclerosis.

Breast tumor cell migration in response to SDF-1 (CXCL12). SDF-1 is a chemokine that is normally produced in the bone marrow for hematapoeisis. Recent studies find that breast tumor cells can metastasize to bone by co-opting this chemokine signaling system.


Approach:

We want to understand how specific signaling mechanisms are translated into biological activities during migration.


Rho Signaling:

Rho Signaling: The dynamics of cell adhesion and the actin cytoskeleton are the primary drivers of cell motility. In 1990, it was observed that the small GTPase RhoA had profound affects on the shape of cells. Since that time, the importance of the family of Rho GTPases has grown such that they are considered the key signaling molecules that regulate cell migration. Rho GTPases integrate input from cell surface receptors and translate it into changes in cell adhesion and the cytoskeleton, thereby driving migration. Our research focuses on RhoA signaling and how it regulates cell adhesion and the cytoskeleton during cell migration. We have found that RhoA is important for defining the “back” end of a migrating cell. In the absence of RhoA, cells develop several “front” ends that compete with each other. This results in a cell that cannot undergo directional migration because it does not know front from back.


Techniques:

Proteomics to probe the ROCK signaling complex

Live-cell imaging- our sophisticated system allows us to study the dynamics of signaling molecules, structural molecules and cell behavior using cutting edge fluorescent probes.

Modern molecular techniques for analysis of signaling pathways