Parent Lab Research

The property of sensing and initiating directional migration in response to external cues is a fundamental property of biological systems. In metazoans, for instance, this behavior is essential for a variety of fundamental processes including embryogenesis, adult tissue homeostasis, inflammation and immune responses, as well as metastatic invasion. Our research program aims to understand how cells detect and respond to external chemotactic signals and, in particular, how the spatial and temporal relay of chemotactic signals between cells impact single and group cell migration. The cornerstone of our approach to studying this paradigm is the tagging of signaling protein effectors with the green fluorescent protein (GFP) to visualize where, when and how relevant cascades are activated in live cells. Along with several other experimental tools, the outcome of our live imaging efforts led us to propose novel mechanisms to explain how chemotactic gradients are transduced and amplified in simple and complex biological settings.

Our studies of chemotaxis involve three distinct model systems with complementary virtues:

1. The social amoebae Dictyostelium discoideum, a relatively simple system, genetically tractable and readily amenable to biochemistry. 

 

2. Mammalian neutrophils, which function largely like Dictyostelium and allow the study of acute and chronic inflammation in a physiologically relevant fashion.

 

 

 3. Breast cancer metastatic cell lines, which provide a unique perspective into a devastating aspect of tumor biology. 

 

In addition to combining biochemical, cell biological and genetic approaches, our group benefits from a long-standing collaboration with physicists to quantitatively describe the movements, with single cell resolution, of large groups of cells, and extract metrics that are relevant to the biological responses being studied.

 

Such a plurality of model systems, along with a trans-disciplinary approach to their study, empowers us to understand signal transduction pathways in complex physiological settings, and directly translate our findings to clinically important processes such as inflammation, immune responses, tissue repair, and cancer metastasis.